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CompletedNCT02396758OPTALYSE PEUpdated Jul 19, 2021Results posted

Optimum Duration of Acoustic Pulse Thrombolysis Procedure in Acute Pulmonary Embolism

A Phase 4 interventional study of Ekosonic® Endovascular Device ultrasonic infusion catheter and Recombinant tissue plasminogen activator in Pulmonary Embolism and Thrombosis, sponsored by Boston Scientific Corporation. Completed at 21 sites in 2 countries. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2021-07-19.

Sponsored by Boston Scientific Corporation · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
131
Allocation
Randomized
Ages
18 Years to 75 Years
Sex
All
01

Study summary

The objective is to determine the optimum dose of thrombolytic and duration of the ultrasound procedure (together defined as the APT Procedure) as a treatment for acute submassive pulmonary embolism (PE). Symptomatic submassive PE are participants with acute (less than or equal to [≤]14 days) PE with normal systemic arterial blood pressure (greater than [>] 90 mmHg) and evidence of RV dysfunction (right ventricular to left ventricular diameter ratio, that is; RV/LV ratio greater than or equal to [≥] 0.9). Participants with submassive PE will be randomized to one of four APT treatment groups: ultrasound of 2 and 6 hours (hrs) with r-tPA 2 milligrams (mg)/hr/catheter and ultrasound 4 and 6 hours with r-tPA, 1 mg/hr/catheter. On 08 June 2016, randomization into treatment group 4 (APT/6 hours-r-tPA/2 mg/hr/catheter) was closed following a reported intracranial hemorrhage (ICH) and death in a study participant in this arm.

Read the detailed description

This study is designed to investigate the lowest recombinant tissue plasminogen activator (r-tPA) dose-ultrasound treatment time required to achieve the same reductions in thrombus burden and associated improvement in physiologic parameters demonstrated in ULTIMA (EKOS 08 [NCT01166997]) and SEATTLE II (EKOS 09 [NCT01513759]). Results of this study are intended to inform the study design for further studies of the Acoustic Pulse Thrombolysis (APT) Procedure. Analysis of the first 100 evaluable participants in the United States study suggested a degree of equipoise between treatment groups 1, 2 and 3 of the protocol and therefore the sample size has been extended and additional sites in the United Kingdom (UK) National Health Service included, with a view to adding to the findings of the OPTALYSE study from sites in the UK and increasing the number of participants treated by treatment protocol.

02

Conditions studied

  • Pulmonary Embolism and Thrombosis
03

In context

Pulmonary Embolism

739 studies on the registry are indexed under Pulmonary Embolism; 159 are open to participants now.

This study's enrollment of 131 is below the median of 150 across 381 interventional studies indexed under Pulmonary Embolism.

Browse Pulmonary Embolism studies →

Lead sponsor

Boston Scientific Corporation is the lead sponsor of 517 studies on the registry; 38 are open to participants now.

Of its 64 completed or terminated interventional studies of FDA-regulated products, 56 (88%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Male or female greater than or equal to (≥) 18 years of age and less than or equal to (≤) 75 years of age.
  2. CTA evidence of proximal PE (filling defect in at least one main or lobar pulmonary artery).
  3. PE symptom duration ≤14 days.
  4. Submassive PE: RV/LV diameter ≥ 0.9 from CTA and hemodynamically stable. For Participants in UK Sites: Submassive PE: RV/LV diameter ≥ 0.9 from CTA, hemodynamically stable and an elevated biomarker.
  5. Must be treated within 48 hours of diagnosis of PE by CTA.
  6. Signed Informed consent obtained from subject or Legally Authorized Representative.

Exclusion criteria

Exclusion Criteria:

  1. Stroke or transient ischemic attack (TIA), head trauma, or other active intracranial or intraspinal disease within one year.
  2. Recent (within one month) or active bleeding from a major organ.
  3. Major surgery within seven days of screening for study enrollment.
  4. Clinician deems the subject high-risk for catastrophic bleeding.
  5. History of heparin-induced thrombocytopenia (HIT).
  6. Catheter-based pharmacomechanical treatment for PE within 3 days of study enrollment.
  7. Systolic blood pressure (SBP) less than 90 mm Hg and/or use of vasopressors.
  8. Cardiac arrest (including pulseless electrical activity and asystole) requiring active cardiopulmonary resuscitation (CPR).
  9. Evidence of irreversible neurological compromise.
  10. Life expectancy \< one year. For Participants in UK Sites: Life expectancy \< one year or enrollment in hospice care.
  11. Use of thrombolytics or glycoprotein IIb/IIIa antagonists within 3 days prior to inclusion in the study.
  12. Out-of-Range Laboratory Values: Hematocrit \< 30%, Platelets \< 100 thousand/microliter (μL), International normalized ratio (INR) > 3.
  13. Creatinine outside the normal range for the treating institution.
  14. Participant is pregnant (positive pregnancy test; women of childbearing capacity must be tested) or breast feeding.
  15. Active cancer (metastatic, progressive, or treated within the last 6 months). Exception: participants with non-melanoma primary skin cancers are eligible to participate in the study.
  16. Known allergy, hypersensitivity, or thrombocytopenia from heparin, r-tPA, or iodinated contrast except for mild-moderate contrast allergies for which steroid pre-medication can be used.
  17. History of any hematologic disease potentially involving abnormal platelet number or function.
05

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
131 participants (actual)

Study arms

  • Experimental
    APT/2 Hours-r-tPA/2 mg/hr/Catheter

    A total of 4 or 8 mg r-tPA (as 2 mg/hour \[hr\]/catheter) will be delivered through Ekosonic® Endovascular Device (EKOS) ultrasonic infusion catheter for 2 hrs.

    Device: Ekosonic® Endovascular Device ultrasonic infusion catheter · Biological: Recombinant tissue plasminogen activator

  • Experimental
    APT/4 Hours-r-tPA/1 mg/hr/Catheter

    A total of 4 or 8 mg r-tPA (as 1 mg/hr/catheter) will be delivered through EKOS ultrasonic infusion catheter for 4 hrs.

    Device: Ekosonic® Endovascular Device ultrasonic infusion catheter · Biological: Recombinant tissue plasminogen activator

  • Experimental
    APT/6 Hours-r-tPA/1 mg/hr/Catheter

    A total of 6 or 12 mg r-tPA (as 1 mg/hr/catheter) will be delivered through EKOS ultrasonic infusion catheter for 6 hrs.

    Device: Ekosonic® Endovascular Device ultrasonic infusion catheter · Biological: Recombinant tissue plasminogen activator

  • Experimental
    APT/6 Hours-r-tPA/2 mg/hr/Catheter

    A total of 12 or 24 mg r-tPA (as 2 mg/hr/catheter) will be delivered through EKOS ultrasonic infusion catheter for 6 hrs.

    Device: Ekosonic® Endovascular Device ultrasonic infusion catheter · Biological: Recombinant tissue plasminogen activator

Interventions

  • DeviceEkosonic® Endovascular Device ultrasonic infusion catheter

    r-tPA will be administered via EKOS.

    Also known as: Acoustic Pulse Thrombolysis Procedure (APT Procedure), EKOS

  • BiologicalRecombinant tissue plasminogen activator

    Recombinant tissue plasminogen activator will be administered as per the dose and schedule specified in the arm.

    Also known as: r-tPA

06

What researchers measure

Primary outcomes

  1. Change From Baseline in the Right Ventricle (RV) Diameter-to-Left Ventricle (LV) Diameter Ratio to 48 ± 6 Hours After the Start of the APT Procedure

    Change from baseline in RV/LV will be determined by computed tomographic angiography (CTA).

    Time frame: Change from Baseline to 48 hrs ± 6 hours

  2. Number of Participants With Major Bleeding Within 72 Hours After Initiating the APT Procedure

    Criteria for major bleeding events, as defined by the International Society on Thrombosis and Haemostasis (ISTH): 1. Fatal bleeding and/or; 2. Symptomatic bleeding in a critical area or organ (intracranial, intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, or intramuscular with compartment syndrome) and/or; 3. Bleeding causing a fall in hemoglobin level of 20 grams/liter (g/L) or more, or leading to transfusion of two or more units of whole blood or red blood cells.

    Time frame: Day 3 (within 72 hours after initiating the APT procedure)

Secondary outcomes

  1. Percentage of Participants With Treatment Success of an APT Procedure

    Treatment success of an APT procedure will be assessed by an Adjudication Committee that is blinded to the participant's treatment. The criteria for treatment success are defined as follows: A decrease in RV/LV from baseline to 48 hours after the start of the procedure of at least 0.2; and no life-threatening adverse events related to PE or its treatment through 30 days after the start of the APT procedure.

    Time frame: From Baseline up to Day 30

  2. Change From Baseline in RV/LV at Days 0, 2, 30, 90, and 365, as Assessed by Echocardiograph.

    An echocardiogram was obtained at specified timepoints to evaluate RV/LV.

    Time frame: Baseline (Day -2 [within -48 hrs of APT start]), Day 0 (within 4 hours after APT end), Day 2 (48 [± 6] hrs of APT start), Day 30 (± 5 days), Day 90 (± 10 days) and Day 365 (± 14 days)

  3. Change From Baseline in Tricuspid Annular Plane Systolic Excursion (TAPSE) at Days 0, 2, 30, 90, and 365, as Assessed by Echocardiograph

    The extent of displacement of the tricuspid valves, termed as TAPSE was measured at specified timepoints using echocardiogram.

    Time frame: Baseline (Day -2 [within -48 hrs of APT start]), Day 0 (within 4 hours after APT end), Day 2 (48 [± 6] hrs of APT start), Day 30 (± 5 days), Day 90 (± 10 days) and Day 365 (± 14 days)

  4. Change From Baseline in Estimated Right Ventricular Systolic Pressure (RVSP) at Days 0, 2, 30, 90, and 365, as Assessed by Echocardiograph

    RVSP was measured at specified timepoints using echocardiogram.

    Time frame: Baseline (Day -2 [within -48 hrs of APT start]), Day 0 (within 4 hours after APT end), Day 2 (48 [± 6] hrs of APT start), Day 30 (± 5 days), Day 90 (± 10 days) and Day 365 (± 14 days)

  5. Percentage of Participants With Collapse of the Inferior Vena Cava (IVC) With Respiration at Days 0, 2, 30, 90, and 365, as Assessed by Echocardiograph

    The collapse of IVC was measured at specified timepoints using echocardiogram.

    Time frame: Baseline (Day -2 [within -48 hrs of APT start]), Day 0 (within 4 hours after APT end), Day 2 (48 [± 6] hrs of APT start), Day 30 (± 5 days), Day 90 (± 10 days) and Day 365 (± 14 days)

  6. Change From Baseline in Thrombus Burden by Miller Score as Assessed by Pulmonary Arteriogram (PAgram) at Day 0

    Miller score is composed of a score for arterial obstruction (objective score) and a score for reduction of peripheral perfusion of lungs (subjective evaluation). Right pulmonary artery (PA) is assigned 9 segmental arteries (3 to the upper, 2 to the middle, and 4 to the lower lobe), and left PA is assigned only 7 segmental arteries (2 to the upper, 2 to the lingula, and 3 to the lower lobe). Presence of segmental emboli, regardless of the degree of obstruction, is scored 1 point. Proximal emboli to the segmental level are scored a value equal to the number of segmental arteries arising distally. Maximal score of obstruction=16. Reduction of peripheral perfusion is scored by dividing each lung into upper, middle, and lower zones and by using a 4-point scale: 0=normal perfusion; 1=moderately reduced perfusion; 2=severely reduced perfusion; 3=no perfusion. Maximal score of reduced perfusion=18. Thus, the maximal Miller score =34. Higher Miller score=more thrombus burden.

    Time frame: Baseline, Day 0 (within 4 hours after APT end)

  7. Change From Baseline in Thrombus Burden by Modified Miller Score as Assessed by CTA Scan at 48 ± 6 Hours After the Start of the APT Procedure

    Modified miller score quantifies thrombus burden on CTA scans. Each segmental pulmonary artery (9 on the right, 7 on the left) that is fully or partly occluded by thrombus is given a score of 1. Any further proximal involves vessels score the number of segmental branches distal to that vessel, thereby giving a modified miller score of 0 (no thrombus) to 16 (thrombus in all segmental arteries or saddle embolism).

    Time frame: From Baseline to 48 hrs ± 6 hours

  8. Change in 6 Minute Walk (6MW) Distance From Day 30 to Day 90 and 365

    The 6 minute Walk Test is a measure of functional exercise capacity. Participants will be asked to walk as far as possible within a 6-minute period, and the distance covered at the end will be noted and recorded.

    Time frame: Days 30, 90, 365

  9. Change in Borg Scale Score Before and After 6MW Distance Test at Days 30, 90, and 365

    Borg is a 10-point scale rating the maximum level of dyspnea (difficulty in breathing) and fatigue experienced before and after the 6MW distance test. Scores ranges from 0 (for no shortness of breath, or no fatigue) to 10 (for the greatest shortness of breath ever experienced, or maximum amount of fatigue felt). Higher scores indicates worse outcome.

    Time frame: Days 30, 90, and 365

  10. Number of Participants Who Received Oxygen Therapy

    Oxygen source is categorized as room air, nasal prongs, mask, and intubated.

    Time frame: Days 30, 90, and 365

  11. Change in Participant Reported Outcomes Measurement Information System Physical Function (PROMIS-PF) 6b Score From Day 30 to Day 365

    PROMIS-PF 6b questionnaire is developed by including 2-items from item-improved Health Assessment Questionnaire (HAQ) and 4-items from item-improved Physical Function-10 (PF-10) instruments. Both of these instruments assess participant's present abilities. Both "Item-Improved instruments" have 5-response options: HAQ - 1="without any difficulty," 2="with a little difficulty," 3="with some difficulty," 4="with much difficulty," 5="unable to do"; PF-10 - 1="not at all," 2="very little," 3="somewhat," 4="quite a lot," 5="cannot do." Total score is the average of all scores of component items, which ranges from 0 (no disability) to 100 (worst disability).

    Time frame: Day 30, Day 365

  12. Change in Pulmonary Embolism Quality of Life (PEmb-QOL) Score From Day 30 to Day 365

    The PEmb-QoL questionnaire contains 6 dimensions that has been created based on the contents of the items, frequency of complaints (Question \[Q\]1; score range: 1 \[every day\] to 5 \[never\]), activities of daily living (ADL) limitations (Q4; score range: 1 \[limited a lot\] to 3 \[not at all\]), work-related problems (Q5; response: yes/no), social limitations (Q6; score range: 1 \[not at all\] to 5 \[extremely\]), intensity of complaints (Q7 \[pain in chest/shoulders\]/8 \[breathlessness\]; score range: 1 \[none\] to 6 \[very serious\]) and emotional complaints (Q9; score range: 1 \[at all times\] to 6 \[none of the times\]). Total Score for all dimensions are calculated by the sum of the scores for each item of the dimension divided by the number of items. Total score ranges from 1 (better quality of life) to 100 (worst quality of life). Higher scores indicate poorer outcome (decreased quality of life). Questions 1, 4, 5, and 9 are reverse scored. Questions 2 and 3 provide descriptive information.

    Time frame: Day 30, Day 365

  13. Number of Participants Who Encountered Technical Procedural Complications

    Technical complications associated with the use of the EKOS device will be recorded during catheter placement in the pulmonary artery and during the infusion procedure.

    Time frame: From device placement through Day 2

  14. Number of Participants With Symptomatic Recurrent Pulmonary Embolism (Per Adjudication)

    Number of participants with symptomatic recurrent pulmonary embolism up to 365 days following the APT procedure, were reported. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

    Time frame: From Baseline up to Day 365

  15. Number of Participants Who Die Due to Any Cause

    Number of participants who died due to any cause for up to 365 days following the APT procedure, were reported.

    Time frame: From Baseline up to Day 365

  16. For Participants of UK Sites: Freedom From Major Harm Occurring Between Enrolment and 30 Days

    Number of UK participants with freedom from major harms assessed by Safety Monitor using the following criteria: 1) Mortality - all cause and PE related; 2) Cardiovascular (CV) collapse defined as one or more of the following: a) Greater than (\>) 40 millimeters of mercury (mmHg) drop in systolic blood pressure (SBP) (for \>15 minutes from documented blood pressure as an in-patient) despite intravenous (IV) fluid challenge and absence of new atrial arrhythmia; b) Requirement for emergency systemic thrombolysis; c) Requirement for emergency surgical embolectomy ; d) Requirement for vasopressors; e)and/or Intubation/Ventilation; 3) Major bleeding per ISTH; 4) Recurrent PE (confirmed by imaging); and/or 5) Surgical correction of device related complication. Due to changes in the protocol, there were no subjects enrolled in the UK in Treatment Arm 4.

    Time frame: From Baseline up to Day 30

  17. For Participants of UK Sites:Change in EuroQual - 5 Dimensions - 5 Levels (EQ-5D-5L) Score From Day 30 to Day 365

    The EQ-5D-5L consists of 2 parts - the descriptive system (Index Score) and the EQ Visual Analogue scale (VAS Score). The EQ-5D-5L descriptive system comprises 5 dimensions (mobility, self care, usual activities, pain/discomfort, anxiety/depression) and each dimension has 5 levels: no problems (1), slight problems (2), moderate problems (3), severe problems (4), and extreme problems (5). Each one digit number expressing the level selected for each dimension is combined into a 5-digit number describing the respondent's heath state. These 5-digit numbers are converted into an index value, where 1 represents full health and 0 is equivalent to death. The EQ VAS records the respondent's self-rated health on a vertical, visual analogue scale with 100 being the best health imaginable and 0 being the worst health imaginable. Due to changes in the protocol, there were no subjects enrolled in the UK in Treatment Arm 4.

    Time frame: Day 30, Day 365

  18. For Participants of UK Sites: Time From Hospital Admission to Diagnosis of PE

    Duration of time between hospital admission and the diagnosis of pulmonary embolism (PE) measured in hours for UK participants.Due to changes in the protocol, there were no subjects enrolled in the UK in Treatment Arm 4.

    Time frame: From Baseline through Day 3

  19. For Participants of UK Sites: Time From Diagnostic Computed Tomography (CT) Scan to Initiation of Treatment for PE

    Duration of time between Diagnostic Computed Tomography (CT) Scan to Initiation of Treatment for pulmonary embolism (PE) measured in hours for UK Participants. Due to changes in the protocol, there were no subjects enrolled in the UK in Treatment Arm 4.

    Time frame: From Baseline through Day 3

  20. For Participants of UK Sites: Time in Each Level of Care (Level 0 and 1; Level 2; and/or Level 3) Through Discharge

    Levels are defined according to National Framework Document: Level 0 - normal acute ward care (patients whose needs can be met through normal ward care in an acute hospital), Level 1 - acute ward care, with additional advice and support from the critical care team (Patients at risk of their condition deteriorating, or those recently relocated from higher levels of care, whose needs can be met on an acute ward with additional advice from a critical care team), Level 2 - more detailed observation or intervention (requiring more detailed observation or intervention including support for a single failing organ system or post-operative care and those 'stepping down' from higher levels of care) and Level 3 - advanced respiratory support alone, or basic respiratory support together with support of at least two organ systems (includes all complex patients requiring support for multi-organ failure). Due to changes in the protocol, there were no subjects enrolled in the UK in Treatment Arm 4.

    Time frame: From Baseline up to Hospital Discharge

  21. Healthcare Resource Utilization: Team Managing the Participant During Hospitalization - Number of Healthcare Professional (HCP) Specialties Involved. (UK Participants Only)

    Number of Healthcare Professional (HCP) Specialists involved with care of participant during hospitalization of UK participants.Due to changes in the protocol, there were no subjects enrolled in the UK in Treatment Arm 4.

    Time frame: From Baseline up to Day 365

  22. Healthcare Resource Utilization: Number of Healthcare Professionals (HCP) Visits for Venous Thromboembolism (VTE) After Hospitalization and During 12month Follow-up. (UK Participants Only)

    Number of Healthcare Professional (HCP) Specialists involved with care of participant for Venous Thromboembolism (VTE) after hospitalization through 365 days for UK participants. Due to changes in the protocol, there were no subjects enrolled in the UK in Treatment Arm 4.

    Time frame: From Day 30 up to Day 365

  23. Healthcare Resource Utilization: Number of Healthcare Professionals (HCP) Visits for Venous Thromboembolism (VTE) After Hospitalization and During 12 Month Follow-up. (UK Participants Only)

    Number of Healthcare Professional (HCP) Specialists involved with care of participant for Venous Thromboembolism (VTE) after hospitalization through 365 days for UK participants. Due to changes in the protocol, there were no subjects enrolled in the UK in Treatment Arm 4.

    Time frame: From Day 30 up to Day 365

  24. Healthcare Resource Utilization: Number of Hospital Re-Admissions After Hospitalization and During 12 Month Follow-up. (UK Participants Only)

    Number of Hospital Re-Admissions after hospitalization and during 12 month follow-up for UK Participants. Due to changes in the protocol, there were no subjects enrolled in the UK in Treatment Arm 4.

    Time frame: From Day 30 up to Day 365

  25. Healthcare Resource Utilization: Duration of Hospital Re-Admissions After Hospitalization and During 12 Month Follow-up. (UK Participants Only)

    Duration of Hospital Re-Admissions after hospitalization and during 12 month follow-up for UK Participants. Due to changes in the protocol, there were no subjects enrolled in the UK in Treatment Arm 4.

    Time frame: From Day 30 through Day 365

07

Results

Posted Mar 2, 2021

Participant flow

Participant flow — Overall Study
MilestoneAPT/2 Hours-r-tPA/2 mg/hr/CatheterAPT/4 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/2 mg/hr/Catheter
Started38373818
Completed26313413
Not completed12645
Withdrew: Withdrawal by subject2001
Withdrew: Lost to follow-up8533
Withdrew: Death1101
Withdrew: Randomized but not treated1010

Outcome measures

PrimaryChange From Baseline in the Right Ventricle (RV) Diameter-to-Left Ventricle (LV) Diameter Ratio to 48 ± 6 Hours After the Start of the APT Procedure

Change from baseline in RV/LV will be determined by computed tomographic angiography (CTA).

Time frame:
Change from Baseline to 48 hrs ± 6 hours
Reported as:
Mean · ratio
Change From Baseline in the Right Ventricle (RV) Diameter-to-Left Ventricle (LV) Diameter Ratio to 48 ± 6 Hours After the Start of the APT Procedure
ratioAPT/2 Hours-r-tPA/2 mg/hr/CatheterAPT/4 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/2 mg/hr/Catheter
Baseline1.53 ± 0.381.47 ± 0.351.52 ± 0.391.51 ± 0.58
Change at 48 ± 6 hours-0.43 ± 0.35-0.37 ± 0.26-0.41 ± 0.31-0.48 ± 0.51
PrimaryNumber of Participants With Major Bleeding Within 72 Hours After Initiating the APT Procedure

Criteria for major bleeding events, as defined by the International Society on Thrombosis and Haemostasis (ISTH): 1. Fatal bleeding and/or; 2. Symptomatic bleeding in a critical area or organ (intracranial, intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, or intramuscular with compartment syndrome) and/or; 3. Bleeding causing a fall in hemoglobin level of 20 grams/liter (g/L) or more, or leading to transfusion of two or more units of whole blood or red blood cells.

Time frame:
Day 3 (within 72 hours after initiating the APT procedure)
Reported as:
Count of participants · Participants
Number of Participants With Major Bleeding Within 72 Hours After Initiating the APT Procedure
ParticipantsAPT/2 Hours-r-tPA/2 mg/hr/CatheterAPT/4 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/2 mg/hr/Catheter
Number of Participants With Major Bleeding Within 72 Hours After Initiating the APT Procedure0212
SecondaryPercentage of Participants With Treatment Success of an APT Procedure

Treatment success of an APT procedure will be assessed by an Adjudication Committee that is blinded to the participant's treatment. The criteria for treatment success are defined as follows: A decrease in RV/LV from baseline to 48 hours after the start of the procedure of at least 0.2; and no life-threatening adverse events related to PE or its treatment through 30 days after the start of the APT procedure.

Time frame:
From Baseline up to Day 30
Reported as:
Number · Percentage of participants
Percentage of Participants With Treatment Success of an APT Procedure
Percentage of participantsAPT/2 Hours-r-tPA/2 mg/hr/CatheterAPT/4 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/2 mg/hr/Catheter
Percentage of Participants With Treatment Success of an APT Procedure73.9 (53.5 to 87.5)68.0 (48.4 to 82.8)69.2 (50.0 to 83.5)61.6 (38.6 to 79.7)
SecondaryChange From Baseline in RV/LV at Days 0, 2, 30, 90, and 365, as Assessed by Echocardiograph.

An echocardiogram was obtained at specified timepoints to evaluate RV/LV.

Time frame:
Baseline (Day -2 [within -48 hrs of APT start]), Day 0 (within 4 hours after APT end), Day 2 (48 [± 6] hrs of APT start), Day 30 (± 5 days), Day 90 (± 10 days) and Day 365 (± 14 days)
Reported as:
Mean · Ratio
Change From Baseline in RV/LV at Days 0, 2, 30, 90, and 365, as Assessed by Echocardiograph.
RatioAPT/2 Hours-r-tPA/2 mg/hr/CatheterAPT/4 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/2 mg/hr/Catheter
Baseline1.19 ± 0.251.20 ± 0.231.13 ± 0.171.20 ± 0.35
Change at 48 hrs post-APT-0.23 ± 0.22-0.29 ± 0.25-0.17 ± 0.20-0.29 ± 0.32
Change at Day 30 post-APT-0.38 ± 0.27-0.37 ± 0.23-0.30 ± 0.20-0.37 ± 0.39
Change at Day 90 follow-up-0.41 ± 0.29-0.39 ± 0.23-0.31 ± 0.22-0.43 ± 0.41
Change at Day 365 follow-up-0.44 ± 0.30-0.46 ± 0.24-0.35 ± 0.15-0.32 ± 0.13
SecondaryChange From Baseline in Tricuspid Annular Plane Systolic Excursion (TAPSE) at Days 0, 2, 30, 90, and 365, as Assessed by Echocardiograph

The extent of displacement of the tricuspid valves, termed as TAPSE was measured at specified timepoints using echocardiogram.

Time frame:
Baseline (Day -2 [within -48 hrs of APT start]), Day 0 (within 4 hours after APT end), Day 2 (48 [± 6] hrs of APT start), Day 30 (± 5 days), Day 90 (± 10 days) and Day 365 (± 14 days)
Reported as:
Mean · Millimeters
Change From Baseline in Tricuspid Annular Plane Systolic Excursion (TAPSE) at Days 0, 2, 30, 90, and 365, as Assessed by Echocardiograph
MillimetersAPT/2 Hours-r-tPA/2 mg/hr/CatheterAPT/4 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/2 mg/hr/Catheter
Baseline16.32 ± 5.0617.20 ± 5.1416.39 ± 5.3618.02 ± 5.54
Change at 4 hrs post-APT0.27 ± 6.090.79 ± 4.860.51 ± 4.682.17 ± 4.15
Change at 48 hrs post-APT2.86 ± 4.561.75 ± 4.652.61 ± 4.823.34 ± 6.14
Change at Day 30 post-APT5.42 ± 5.595.39 ± 4.642.36 ± 4.752.26 ± 5.55
Change at Day 90 follow-up6.32 ± 5.643.69 ± 5.443.97 ± 6.292.07 ± 5.86
Change at Day 365 follow-up6.83 ± 5.885.22 ± 4.724.79 ± 5.973.50 ± 5.98
SecondaryChange From Baseline in Estimated Right Ventricular Systolic Pressure (RVSP) at Days 0, 2, 30, 90, and 365, as Assessed by Echocardiograph

RVSP was measured at specified timepoints using echocardiogram.

Time frame:
Baseline (Day -2 [within -48 hrs of APT start]), Day 0 (within 4 hours after APT end), Day 2 (48 [± 6] hrs of APT start), Day 30 (± 5 days), Day 90 (± 10 days) and Day 365 (± 14 days)
Reported as:
Mean · Millimeters
Change From Baseline in Estimated Right Ventricular Systolic Pressure (RVSP) at Days 0, 2, 30, 90, and 365, as Assessed by Echocardiograph
MillimetersAPT/2 Hours-r-tPA/2 mg/hr/CatheterAPT/4 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/2 mg/hr/Catheter
Baseline31.59 ± 14.8936.64 ± 19.0235.57 ± 16.3225.75 ± 11.09
Change at 4 hrs post-APT-2.18 ± 13.04-10.87 ± 15.32-3.54 ± 14.232.13 ± 13.74
Change at 48 hrs post-APT0.98 ± 9.36-5.35 ± 18.45-9.31 ± 10.53-7.80 ± 11.69
Change at Day 30 post-APT-7.92 ± 11.69-13.84 ± 15.47-14.06 ± 15.41-4.86 ± 18.07
Change at Day 90 follow-up-8.30 ± 15.38-15.60 ± 16.90-16.39 ± 24.18-7.08 ± 15.30
Change at Day 365 follow-up-9.78 ± 12.79-12.87 ± 13.17-18.96 ± 12.23-7.16 ± 16.57
SecondaryPercentage of Participants With Collapse of the Inferior Vena Cava (IVC) With Respiration at Days 0, 2, 30, 90, and 365, as Assessed by Echocardiograph

The collapse of IVC was measured at specified timepoints using echocardiogram.

Time frame:
Baseline (Day -2 [within -48 hrs of APT start]), Day 0 (within 4 hours after APT end), Day 2 (48 [± 6] hrs of APT start), Day 30 (± 5 days), Day 90 (± 10 days) and Day 365 (± 14 days)
Reported as:
Number · percentage of participants
Percentage of Participants With Collapse of the Inferior Vena Cava (IVC) With Respiration at Days 0, 2, 30, 90, and 365, as Assessed by Echocardiograph
percentage of participantsAPT/2 Hours-r-tPA/2 mg/hr/CatheterAPT/4 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/2 mg/hr/Catheter
Baseline96.55 (82.82 to 99.39)100.00 (88.30 to 100.00)96.00 (80.46 to 99.29)81.25 (56.99 to 93.41)
4 hrs post-APT89.66 (73.61 to 96.42)96.00 (80.46 to 99.29)89.29 (72.80 to 96.29)87.50 (63.98 to 96.50)
48 hrs post-APT100.00 (86.20 to 100.00)100.00 (88.97 to 100.00)92.86 (77.35 to 98.02)82.35 (58.97 to 93.81)
Day 30 post-APT96.55 (82.82 to 99.39)96.30 (81.72 to 99.34)96.67 (83.33 to 99.41)92.31 (66.69 to 98.63)
Day 90 post-APT100.00 (86.68 to 100.00)92.00 (75.03 to 97.78)96.43 (82.29 to 99.37)100.00 (75.75 to 100.00)
Day 365 post-APT94.44 (74.24 to 99.01)100.00 (85.69 to 100.00)86.96 (67.87 to 95.46)83.33 (55.20 to 95.30)
SecondaryChange From Baseline in Thrombus Burden by Miller Score as Assessed by Pulmonary Arteriogram (PAgram) at Day 0

Miller score is composed of a score for arterial obstruction (objective score) and a score for reduction of peripheral perfusion of lungs (subjective evaluation). Right pulmonary artery (PA) is assigned 9 segmental arteries (3 to the upper, 2 to the middle, and 4 to the lower lobe), and left PA is assigned only 7 segmental arteries (2 to the upper, 2 to the lingula, and 3 to the lower lobe). Presence of segmental emboli, regardless of the degree of obstruction, is scored 1 point. Proximal emboli to the segmental level are scored a value equal to the number of segmental arteries arising distally. Maximal score of obstruction=16. Reduction of peripheral perfusion is scored by dividing each lung into upper, middle, and lower zones and by using a 4-point scale: 0=normal perfusion; 1=moderately reduced perfusion; 2=severely reduced perfusion; 3=no perfusion. Maximal score of reduced perfusion=18. Thus, the maximal Miller score =34. Higher Miller score=more thrombus burden.

Time frame:
Baseline, Day 0 (within 4 hours after APT end)
Reported as:
Mean · units on a scale
Change From Baseline in Thrombus Burden by Miller Score as Assessed by Pulmonary Arteriogram (PAgram) at Day 0
units on a scaleAPT/2 Hours-r-tPA/2 mg/hr/CatheterAPT/4 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/2 mg/hr/Catheter
Baseline23.71 ± 3.2123.29 ± 6.0024.21 ± 3.0122.93 ± 2.99
Change at 4 hrs post-APT-1.00 ± 3.46-2.29 ± 5.62-3.11 ± 3.89-9.20 ± 3.11
SecondaryChange From Baseline in Thrombus Burden by Modified Miller Score as Assessed by CTA Scan at 48 ± 6 Hours After the Start of the APT Procedure

Modified miller score quantifies thrombus burden on CTA scans. Each segmental pulmonary artery (9 on the right, 7 on the left) that is fully or partly occluded by thrombus is given a score of 1. Any further proximal involves vessels score the number of segmental branches distal to that vessel, thereby giving a modified miller score of 0 (no thrombus) to 16 (thrombus in all segmental arteries or saddle embolism).

Time frame:
From Baseline to 48 hrs ± 6 hours
Reported as:
Mean · units on a scale
Change From Baseline in Thrombus Burden by Modified Miller Score as Assessed by CTA Scan at 48 ± 6 Hours After the Start of the APT Procedure
units on a scaleAPT/2 Hours-r-tPA/2 mg/hr/CatheterAPT/4 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/2 mg/hr/Catheter
Baseline20.72 ± 2.7620.00 ± 4.1420.92 ± 2.3120.44 ± 4.12
Change at 48 hrs post-APT-1.24 ± 1.71-2.20 ± 2.29-2.62 ± 2.47-5.22 ± 5.83
SecondaryChange in 6 Minute Walk (6MW) Distance From Day 30 to Day 90 and 365

The 6 minute Walk Test is a measure of functional exercise capacity. Participants will be asked to walk as far as possible within a 6-minute period, and the distance covered at the end will be noted and recorded.

Time frame:
Days 30, 90, 365
Reported as:
Mean · meters
Change in 6 Minute Walk (6MW) Distance From Day 30 to Day 90 and 365
metersAPT/2 Hours-r-tPA/2 mg/hr/CatheterAPT/4 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/2 mg/hr/Catheter
Day 30355.4 ± 78.62366.90 ± 157.76362.3 ± 103.81327.3 ± 99.70
Change at Day 9023.8 ± 133.9870.6 ± 59.6233.8 ± 65.85-6.3 ± 62.98
Change at Day 36521.6 ± 67.332.0 ± 175.1157.9 ± 217.99-1.9 ± 155.78
SecondaryChange in Borg Scale Score Before and After 6MW Distance Test at Days 30, 90, and 365

Borg is a 10-point scale rating the maximum level of dyspnea (difficulty in breathing) and fatigue experienced before and after the 6MW distance test. Scores ranges from 0 (for no shortness of breath, or no fatigue) to 10 (for the greatest shortness of breath ever experienced, or maximum amount of fatigue felt). Higher scores indicates worse outcome.

Time frame:
Days 30, 90, and 365
Reported as:
Median · units on a scale
Change in Borg Scale Score Before and After 6MW Distance Test at Days 30, 90, and 365
units on a scaleAPT/2 Hours-r-tPA/2 mg/hr/CatheterAPT/4 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/2 mg/hr/Catheter
Day 30: Dyspnea0.75 (0 to 2)0 (0 to 2)0.5 (0 to 2)0 (0 to 2)
Day 30: Fatigue0.25 (0 to 1.3)0 (0 to 0.5)0 (0 to 1)0 (0 to 0)
Day 90: Dyspnea1 (0 to 2)0.5 (0 to 1)0.5 (0 to 2)0 (0 to 3)
Day 90: Fatigue0 (0 to 1)0 (0 to 1)0 (0 to 0.5)0 (0 to 0.5)
Day 365: Dyspnea0.25 (0 to 2)0.5 (0 to 1)0 (0 to 1)0 (0 to 3)
Day 365: Fatigue0 (0 to 1)0 (0 to 1)0 (0 to 1)0 (0 to 0)
SecondaryNumber of Participants Who Received Oxygen Therapy

Oxygen source is categorized as room air, nasal prongs, mask, and intubated.

Time frame:
Days 30, 90, and 365
Reported as:
Count of participants · Participants
Number of Participants Who Received Oxygen Therapy
ParticipantsAPT/2 Hours-r-tPA/2 mg/hr/CatheterAPT/4 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/2 mg/hr/Catheter
Day 30: Before 6MW test - Room air29303410
Day 30: After 6MW test - Room air28303310
Day 90: Before 6MW test - Room air26303610
Day 90: After 6MW test - Room air26303610
Day 365: Before 6MW test - Room air21273010
Day 365: After 6MW test - Room air21283010
SecondaryChange in Participant Reported Outcomes Measurement Information System Physical Function (PROMIS-PF) 6b Score From Day 30 to Day 365

PROMIS-PF 6b questionnaire is developed by including 2-items from item-improved Health Assessment Questionnaire (HAQ) and 4-items from item-improved Physical Function-10 (PF-10) instruments. Both of these instruments assess participant's present abilities. Both "Item-Improved instruments" have 5-response options: HAQ - 1="without any difficulty," 2="with a little difficulty," 3="with some difficulty," 4="with much difficulty," 5="unable to do"; PF-10 - 1="not at all," 2="very little," 3="somewhat," 4="quite a lot," 5="cannot do." Total score is the average of all scores of component items, which ranges from 0 (no disability) to 100 (worst disability).

Time frame:
Day 30, Day 365
Reported as:
Mean · units on a scale
Change in Participant Reported Outcomes Measurement Information System Physical Function (PROMIS-PF) 6b Score From Day 30 to Day 365
units on a scaleAPT/2 Hours-r-tPA/2 mg/hr/CatheterAPT/4 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/2 mg/hr/Catheter
Day 3042.00 ± 10.90543.86 ± 7.98044.53 ± 6.69541.40 ± 13.238
Change at Day 3653.61 ± 7.1404.91 ± 8.9092.14 ± 8.1844.39 ± 8.699
SecondaryChange in Pulmonary Embolism Quality of Life (PEmb-QOL) Score From Day 30 to Day 365

The PEmb-QoL questionnaire contains 6 dimensions that has been created based on the contents of the items, frequency of complaints (Question \[Q\]1; score range: 1 \[every day\] to 5 \[never\]), activities of daily living (ADL) limitations (Q4; score range: 1 \[limited a lot\] to 3 \[not at all\]), work-related problems (Q5; response: yes/no), social limitations (Q6; score range: 1 \[not at all\] to 5 \[extremely\]), intensity of complaints (Q7 \[pain in chest/shoulders\]/8 \[breathlessness\]; score range: 1 \[none\] to 6 \[very serious\]) and emotional complaints (Q9; score range: 1 \[at all times\] to 6 \[none of the times\]). Total Score for all dimensions are calculated by the sum of the scores for each item of the dimension divided by the number of items. Total score ranges from 1 (better quality of life) to 100 (worst quality of life). Higher scores indicate poorer outcome (decreased quality of life). Questions 1, 4, 5, and 9 are reverse scored. Questions 2 and 3 provide descriptive information.

Time frame:
Day 30, Day 365
Reported as:
Mean · units on a scale
Change in Pulmonary Embolism Quality of Life (PEmb-QOL) Score From Day 30 to Day 365
units on a scaleAPT/2 Hours-r-tPA/2 mg/hr/CatheterAPT/4 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/2 mg/hr/Catheter
Day 3038.30 ± 25.72327.85 ± 20.71524.25 ± 18.10925.63 ± 26.923
Change at Day 365-16.79 ± 16.500-8.86 ± 26.576-8.75 ± 15.549-12.01 ± 14.832
SecondaryNumber of Participants Who Encountered Technical Procedural Complications

Technical complications associated with the use of the EKOS device will be recorded during catheter placement in the pulmonary artery and during the infusion procedure.

Time frame:
From device placement through Day 2
Reported as:
Count of participants · Participants
Number of Participants Who Encountered Technical Procedural Complications
ParticipantsAPT/2 Hours-r-tPA/2 mg/hr/CatheterAPT/4 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/2 mg/hr/Catheter
Number of Participants Who Encountered Technical Procedural Complications0010
SecondaryNumber of Participants With Symptomatic Recurrent Pulmonary Embolism (Per Adjudication)

Number of participants with symptomatic recurrent pulmonary embolism up to 365 days following the APT procedure, were reported. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

Time frame:
From Baseline up to Day 365
Reported as:
Count of participants · Participants
Number of Participants With Symptomatic Recurrent Pulmonary Embolism (Per Adjudication)
ParticipantsAPT/2 Hours-r-tPA/2 mg/hr/CatheterAPT/4 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/2 mg/hr/Catheter
Number of Participants With Symptomatic Recurrent Pulmonary Embolism (Per Adjudication)0110
SecondaryNumber of Participants Who Die Due to Any Cause

Number of participants who died due to any cause for up to 365 days following the APT procedure, were reported.

Time frame:
From Baseline up to Day 365
Reported as:
Count of participants · Participants
Number of Participants Who Die Due to Any Cause
ParticipantsAPT/2 Hours-r-tPA/2 mg/hr/CatheterAPT/4 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/2 mg/hr/Catheter
Number of Participants Who Die Due to Any Cause1101
SecondaryFor Participants of UK Sites: Freedom From Major Harm Occurring Between Enrolment and 30 Days

Number of UK participants with freedom from major harms assessed by Safety Monitor using the following criteria: 1) Mortality - all cause and PE related; 2) Cardiovascular (CV) collapse defined as one or more of the following: a) Greater than (\>) 40 millimeters of mercury (mmHg) drop in systolic blood pressure (SBP) (for \>15 minutes from documented blood pressure as an in-patient) despite intravenous (IV) fluid challenge and absence of new atrial arrhythmia; b) Requirement for emergency systemic thrombolysis; c) Requirement for emergency surgical embolectomy ; d) Requirement for vasopressors; e)and/or Intubation/Ventilation; 3) Major bleeding per ISTH; 4) Recurrent PE (confirmed by imaging); and/or 5) Surgical correction of device related complication. Due to changes in the protocol, there were no subjects enrolled in the UK in Treatment Arm 4.

Time frame:
From Baseline up to Day 30
Reported as:
Count of participants · Participants
For Participants of UK Sites: Freedom From Major Harm Occurring Between Enrolment and 30 Days
ParticipantsAPT/2 Hours-r-tPA/2 mg/hr/CatheterAPT/4 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/2 mg/hr/Catheter
For Participants of UK Sites: Freedom From Major Harm Occurring Between Enrolment and 30 Days10990
SecondaryFor Participants of UK Sites:Change in EuroQual - 5 Dimensions - 5 Levels (EQ-5D-5L) Score From Day 30 to Day 365

The EQ-5D-5L consists of 2 parts - the descriptive system (Index Score) and the EQ Visual Analogue scale (VAS Score). The EQ-5D-5L descriptive system comprises 5 dimensions (mobility, self care, usual activities, pain/discomfort, anxiety/depression) and each dimension has 5 levels: no problems (1), slight problems (2), moderate problems (3), severe problems (4), and extreme problems (5). Each one digit number expressing the level selected for each dimension is combined into a 5-digit number describing the respondent's heath state. These 5-digit numbers are converted into an index value, where 1 represents full health and 0 is equivalent to death. The EQ VAS records the respondent's self-rated health on a vertical, visual analogue scale with 100 being the best health imaginable and 0 being the worst health imaginable. Due to changes in the protocol, there were no subjects enrolled in the UK in Treatment Arm 4.

Time frame:
Day 30, Day 365
Reported as:
Mean · units on a scale
For Participants of UK Sites:Change in EuroQual - 5 Dimensions - 5 Levels (EQ-5D-5L) Score From Day 30 to Day 365
units on a scaleAPT/2 Hours-r-tPA/2 mg/hr/CatheterAPT/4 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/2 mg/hr/Catheter
Day 30 - EQ-5D-5L Index Score0.732 ± 0.26240.819 ± 0.1950.934 ± 0.134—
Day 30- EQ-5D-5L VAS Score66.7 ± 19.0477.8 ± 12.0282.5 ± 7.91—
Change at Day 365 - EQ-5D-5L Index Score0.039 ± 0.0418-0.107 ± 0.252-0.042 ± 0.149—
Change at Day 365 - EQ-5D-5L VAS Score-1.6 ± 35.97-0.4 ± 22.017.1 ± 9.12—
SecondaryFor Participants of UK Sites: Time From Hospital Admission to Diagnosis of PE

Duration of time between hospital admission and the diagnosis of pulmonary embolism (PE) measured in hours for UK participants.Due to changes in the protocol, there were no subjects enrolled in the UK in Treatment Arm 4.

Time frame:
From Baseline through Day 3
Reported as:
Mean · hour
For Participants of UK Sites: Time From Hospital Admission to Diagnosis of PE
hourAPT/2 Hours-r-tPA/2 mg/hr/CatheterAPT/4 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/2 mg/hr/Catheter
For Participants of UK Sites: Time From Hospital Admission to Diagnosis of PE10.77 ± 10.789.30 ± 19.087.29 ± 9.64—
SecondaryFor Participants of UK Sites: Time From Diagnostic Computed Tomography (CT) Scan to Initiation of Treatment for PE

Duration of time between Diagnostic Computed Tomography (CT) Scan to Initiation of Treatment for pulmonary embolism (PE) measured in hours for UK Participants. Due to changes in the protocol, there were no subjects enrolled in the UK in Treatment Arm 4.

Time frame:
From Baseline through Day 3
Reported as:
Mean · hour
For Participants of UK Sites: Time From Diagnostic Computed Tomography (CT) Scan to Initiation of Treatment for PE
hourAPT/2 Hours-r-tPA/2 mg/hr/CatheterAPT/4 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/2 mg/hr/Catheter
For Participants of UK Sites: Time From Diagnostic Computed Tomography (CT) Scan to Initiation of Treatment for PE25.33 ± 12.5824.53 ± 13.9330.08 ± 18.42—
SecondaryFor Participants of UK Sites: Time in Each Level of Care (Level 0 and 1; Level 2; and/or Level 3) Through Discharge

Levels are defined according to National Framework Document: Level 0 - normal acute ward care (patients whose needs can be met through normal ward care in an acute hospital), Level 1 - acute ward care, with additional advice and support from the critical care team (Patients at risk of their condition deteriorating, or those recently relocated from higher levels of care, whose needs can be met on an acute ward with additional advice from a critical care team), Level 2 - more detailed observation or intervention (requiring more detailed observation or intervention including support for a single failing organ system or post-operative care and those 'stepping down' from higher levels of care) and Level 3 - advanced respiratory support alone, or basic respiratory support together with support of at least two organ systems (includes all complex patients requiring support for multi-organ failure). Due to changes in the protocol, there were no subjects enrolled in the UK in Treatment Arm 4.

Time frame:
From Baseline up to Hospital Discharge
Reported as:
Mean · hour
For Participants of UK Sites: Time in Each Level of Care (Level 0 and 1; Level 2; and/or Level 3) Through Discharge
hourAPT/2 Hours-r-tPA/2 mg/hr/CatheterAPT/4 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/2 mg/hr/Catheter
Level 0 and 174.64 ± 100.2057.04 ± 40.3664.39 ± 41.70—
Level 286.77 ± 45.8462.34 ± 18.8294.56 ± 84.96—
Level 3—66.8014.10 ± 2.40—
SecondaryHealthcare Resource Utilization: Team Managing the Participant During Hospitalization - Number of Healthcare Professional (HCP) Specialties Involved. (UK Participants Only)

Number of Healthcare Professional (HCP) Specialists involved with care of participant during hospitalization of UK participants.Due to changes in the protocol, there were no subjects enrolled in the UK in Treatment Arm 4.

Time frame:
From Baseline up to Day 365
Reported as:
Mean · HCP per participant
Healthcare Resource Utilization: Team Managing the Participant During Hospitalization - Number of Healthcare Professional (HCP) Specialties Involved. (UK Participants Only)
HCP per participantAPT/2 Hours-r-tPA/2 mg/hr/CatheterAPT/4 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/2 mg/hr/Catheter
Healthcare Resource Utilization: Team Managing the Participant During Hospitalization - Number of Healthcare Professional (HCP) Specialties Involved. (UK Participants Only)3.9 ± 2.234.2 ± 1.934.0 ± 2.21—
SecondaryHealthcare Resource Utilization: Number of Healthcare Professionals (HCP) Visits for Venous Thromboembolism (VTE) After Hospitalization and During 12month Follow-up. (UK Participants Only)

Number of Healthcare Professional (HCP) Specialists involved with care of participant for Venous Thromboembolism (VTE) after hospitalization through 365 days for UK participants. Due to changes in the protocol, there were no subjects enrolled in the UK in Treatment Arm 4.

Time frame:
From Day 30 up to Day 365
Reported as:
Mean · HCP visits per participant
Healthcare Resource Utilization: Number of Healthcare Professionals (HCP) Visits for Venous Thromboembolism (VTE) After Hospitalization and During 12month Follow-up. (UK Participants Only)
HCP visits per participantAPT/2 Hours-r-tPA/2 mg/hr/CatheterAPT/4 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/2 mg/hr/Catheter
Healthcare Resource Utilization: Number of Healthcare Professionals (HCP) Visits for Venous Thromboembolism (VTE) After Hospitalization and During 12month Follow-up. (UK Participants Only)1.5 ± 0.711.3 ± 0.581.0 ± 0.00—
SecondaryHealthcare Resource Utilization: Number of Healthcare Professionals (HCP) Visits for Venous Thromboembolism (VTE) After Hospitalization and During 12 Month Follow-up. (UK Participants Only)

Number of Healthcare Professional (HCP) Specialists involved with care of participant for Venous Thromboembolism (VTE) after hospitalization through 365 days for UK participants. Due to changes in the protocol, there were no subjects enrolled in the UK in Treatment Arm 4.

Time frame:
From Day 30 up to Day 365
Reported as:
Mean · HCP visits per participant
Healthcare Resource Utilization: Number of Healthcare Professionals (HCP) Visits for Venous Thromboembolism (VTE) After Hospitalization and During 12 Month Follow-up. (UK Participants Only)
HCP visits per participantAPT/2 Hours-r-tPA/2 mg/hr/CatheterAPT/4 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/2 mg/hr/Catheter
Healthcare Resource Utilization: Number of Healthcare Professionals (HCP) Visits for Venous Thromboembolism (VTE) After Hospitalization and During 12 Month Follow-up. (UK Participants Only)1.5 ± 0.711.3 ± 0.581.0 ± 0.00—
SecondaryHealthcare Resource Utilization: Number of Hospital Re-Admissions After Hospitalization and During 12 Month Follow-up. (UK Participants Only)

Number of Hospital Re-Admissions after hospitalization and during 12 month follow-up for UK Participants. Due to changes in the protocol, there were no subjects enrolled in the UK in Treatment Arm 4.

Time frame:
From Day 30 up to Day 365
Reported as:
Count of participants · Participants
Healthcare Resource Utilization: Number of Hospital Re-Admissions After Hospitalization and During 12 Month Follow-up. (UK Participants Only)
ParticipantsAPT/2 Hours-r-tPA/2 mg/hr/CatheterAPT/4 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/2 mg/hr/Catheter
Healthcare Resource Utilization: Number of Hospital Re-Admissions After Hospitalization and During 12 Month Follow-up. (UK Participants Only)0010
SecondaryHealthcare Resource Utilization: Duration of Hospital Re-Admissions After Hospitalization and During 12 Month Follow-up. (UK Participants Only)

Duration of Hospital Re-Admissions after hospitalization and during 12 month follow-up for UK Participants. Due to changes in the protocol, there were no subjects enrolled in the UK in Treatment Arm 4.

Time frame:
From Day 30 through Day 365
Reported as:
Mean · Days per subject
Healthcare Resource Utilization: Duration of Hospital Re-Admissions After Hospitalization and During 12 Month Follow-up. (UK Participants Only)
Days per subjectAPT/2 Hours-r-tPA/2 mg/hr/CatheterAPT/4 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/2 mg/hr/Catheter
Healthcare Resource Utilization: Duration of Hospital Re-Admissions After Hospitalization and During 12 Month Follow-up. (UK Participants Only)——2 ± 0—

Adverse events

Collected over From Baseline up to Day 365. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
APT/2 Hours-r-tPA/2 mg/hr/Catheter1/37 (2.7%)11/37 (29.7%)9/37 (24.3%)
APT/4 Hours-r-tPA/1 mg/hr/Catheter1/37 (2.7%)15/37 (40.5%)22/37 (59.5%)
APT/6 Hours-r-tPA/1 mg/hr/Catheter0/37 (0%)12/37 (32.4%)10/37 (27%)
APT/6 Hours-r-tPA/2 mg/hr/Catheter1/18 (5.6%)4/18 (22.2%)6/18 (33.3%)
Most frequent serious events
Showing 10 of 51
Most frequent serious events
EventAPT/2 Hours-r-tPA/2 mg/hr/CatheterAPT/4 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/2 mg/hr/Catheter
Chest painGeneral disorders0/371/370/372/18
Pulmonary embolismRespiratory, thoracic and mediastinal disorders1/373/371/370/18
Cardiac arrestCardiac disorders0/370/370/371/18
Intra-abdominal haemorrhageGastrointestinal disorders0/370/370/371/18
Multi-organ failureGeneral disorders1/370/370/371/18
PyrexiaGeneral disorders0/370/370/371/18
PneumoniaInfections and infestations0/370/372/371/18
SepsisInfections and infestations1/370/370/371/18
Septic shockInfections and infestations0/370/371/371/18
Lumbar spinal stenosisMusculoskeletal and connective tissue disorders0/370/370/371/18
Most frequent other events
Showing 10 of 55
Most frequent other events
EventAPT/2 Hours-r-tPA/2 mg/hr/CatheterAPT/4 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/2 mg/hr/Catheter
AnaemiaBlood and lymphatic system disorders2/371/370/372/18
Chest painGeneral disorders2/371/371/372/18
Urinary tract infectionInfections and infestations1/373/370/370/18
RashSkin and subcutaneous tissue disorders0/373/370/370/18
Atrial fibrillationCardiac disorders0/371/370/371/18
Vessel puncture site haemorrhageGeneral disorders0/370/370/371/18
AnxietyPsychiatric disorders1/370/370/371/18
DeliriumPsychiatric disorders0/370/370/371/18
Deep vein thrombosisVascular disorders0/371/370/371/18
Anaemia postoperativeBlood and lymphatic system disorders1/372/371/370/18

Baseline characteristics

Overall number of participants

Age, Continuous
Age, Continuous(years)APT/2 Hours-r-tPA/2 mg/hr/CatheterAPT/4 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/2 mg/hr/CatheterTotal
Median56.0 ± 13.0557.9 ± 13.0357.9 ± 12.358.2 ± 14.057.4 ± 12.84
Sex: Female, Male
Sex: Female, Male(Participants)APT/2 Hours-r-tPA/2 mg/hr/CatheterAPT/4 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/2 mg/hr/CatheterTotal
Female161821762
Male2219171169
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)APT/2 Hours-r-tPA/2 mg/hr/CatheterAPT/4 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/2 mg/hr/CatheterTotal
Caucasian, not of Hispanic origin2424271186
African American, not of Hispanic origin12109637
Hispanic or Latino02002
Asian or Pacific Islander01102
Other20114
Region of Enrollment
Region of Enrollment(participants)APT/2 Hours-r-tPA/2 mg/hr/CatheterAPT/4 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/1 mg/hr/CatheterAPT/6 Hours-r-tPA/2 mg/hr/CatheterTotal
United States28272818101
United Kingdom101010030
08

Study locations

21 sites
  • Cedars Sinai
    Beverly Hills, California 90211, United States
  • Tallahassee Memorial Hospital
    Tallahassee, Florida 32308, United States
  • Florida Hospital Tampa
    Tampa, Florida 33613, United States
  • Piedmont Hospital
    Atlanta, Georgia 30309, United States
  • University Hospital
    Augusta, Georgia 30901, United States
  • St. Vincent Medical Group
    Indianapolis, Indiana 46260, United States
  • Jewish Hospital
    Louisville, Kentucky 40202, United States
  • East Jefferson General Hospital
    Metairie, Louisiana 70006, United States
  • Detroit Medical Center
    Detroit, Michigan 48201, United States
  • Mount Carmel Health System
    Columbus, Ohio 43213, United States
  • UPMC Hamot
    Erie, Pennsylvania 16507, United States
  • Lankenau Medical Center
    Wynnewood, Pennsylvania 19096, United States
  • Vanderbilt University Medical Center
    Nashville, Tennessee 37232, United States
  • Houston Methodist Sugarland Hospital
    Richmond, Texas 77469, United States
  • Inova Alexandria Hospital
    Alexandria, Virginia, United States
  • Providence Sacred Heart Medical Center
    Spokane, Washington 99204, United States
  • Royal Devon & Exeter Hospital
    Exeter, England EX2 5DW, United Kingdom
  • Medway Maritime Hospital
    Gillingham, England ME7 5NY, United Kingdom
  • Royal Free Hospital
    London, England NW3 2QG, United Kingdom
  • St. Thomas Hospital
    London, England SE1 7EH, United Kingdom
  • Ninewells Hospital
    Dundee, Scotland DD1 9SY, United Kingdom
09

References and documents

Publications

  • Piazza G, Sterling KM, Tapson VF, Ouriel K, Sharp ASP, Liu PY, Goldhaber SZ. One-Year Echocardiographic, Functional, and Quality of Life Outcomes After Ultrasound-Facilitated Catheter-Based Fibrinolysis for Pulmonary Embolism. Circ Cardiovasc Interv. 2020 Aug;13(8):e009012. doi: 10.1161/CIRCINTERVENTIONS.120.009012. Epub 2020 Aug 6. PubMed 32757658 ↗
  • Tapson VF, Sterling K, Jones N, Elder M, Tripathy U, Brower J, Maholic RL, Ross CB, Natarajan K, Fong P, Greenspon L, Tamaddon H, Piracha AR, Engelhardt T, Katopodis J, Marques V, Sharp ASP, Piazza G, Goldhaber SZ. A Randomized Trial of the Optimum Duration of Acoustic Pulse Thrombolysis Procedure in Acute Intermediate-Risk Pulmonary Embolism: The OPTALYSE PE Trial. JACC Cardiovasc Interv. 2018 Jul 23;11(14):1401-1410. doi: 10.1016/j.jcin.2018.04.008. PubMed 30025734 ↗

Study documents

  • Study protocol · Oct 15, 2019
  • Statistical analysis plan · Nov 8, 2019

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jul 19, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02396758
Lead sponsor
Boston Scientific Corporation
Collaborators
EKOS Corporation
Responsible party
Sponsor
First posted
Mar 24, 2015
Start date
Jun 12, 2015
Primary completion
Apr 30, 2019
Completion
Jan 30, 2020
Results posted
Mar 2, 2021
Last update
Jul 19, 2021

Study contacts

Victor Tapson, MD
principal investigator · Cedar Sinai, Los Angeles

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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