A Phase 3 interventional study of Mechanical Endovascular Thrombectomy and Intravenous Thrombolysis in Stroke, Acute Ischemic and Medium Vessel Occlusion, sponsored by University of Calgary. Not yet recruiting at 4 sites in Canada. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-30.
Sponsored by University of Calgary · Phase 3, Interventional, and Treatment
This domain will be conducted as part of ACT-GLOBAL platform trial and will have the nested domain name of IMP-ACT. Acute ischemic stroke (AIS) caused by intracranial arterial occlusion remains a major cause of disability and death. Medium vessel occlusion stroke (MeVO), involving distal medium-sized intracranial arteries, accounts for approximately 25-40% of all AIS cases. Despite best medical management, including intravenous thrombolysis, up to 40% of MeVO patients fail to regain functional independence, and mortality remains approximately 10%.
These poor outcomes prompted several randomized trials evaluating endovascular thrombectomy (EVT) for MeVO stroke, including the CIHR-funded ESCAPE-MeVO trial. ESCAPE-MeVO, DISTAL, and DISCOUNT did not demonstrate overall benefit of EVT compared with best medical management, whereas ORIENTAL-MeVO reported benefit in an Asian population. These conflicting findings have resulted in uncertainty regarding optimal MeVO management and suggest that treatment benefit may depend on patient selection.
A potential explanation for the neutral EVT trials is suboptimal reperfusion. In ESCAPE-MeVO, successful reperfusion was achieved in only 75% of patients, leaving substantial room for procedural improvement. At the same time, major procedural complications were infrequent, supporting the feasibility of exploring strategies to enhance reperfusion.
Subgroup analyses from ESCAPE-MeVO suggested that treatment effect may vary according to time from symptom onset and collateral status. Patients treated early after stroke onset and those with favorable collaterals appeared to derive greater benefit from EVT than later presenters or patients with poor collateral circulation. These findings support a more targeted treatment approach in selected MeVO patients.
Intra-arterial thrombolysis (IAT) has emerged as a promising adjunct to EVT. Local delivery of thrombolytic agents may dissolve residual distal thrombi that are inaccessible or unsafe to treat mechanically and may improve both macrovascular and microvascular reperfusion. Because thrombus burden is generally smaller in MeVO stroke, adjunctive IAT may be particularly effective in this population.
However, no randomized trial has evaluated combined EVT and IAT for primary MeVO stroke. This study will address that evidence gap and determine whether adjunctive IAT can improve outcomes in carefully selected patients with MeVO stroke.
MeVO stroke is common and outcomes remain poor despite state-of-the-art treatment. Recent randomized trials identify a subgroup likely to benefit from EVT - patients with favourable collateral status treated early - and emerging evidence suggests that IAT can safely augment EVT reperfusion success. Equipoise in the stroke physician community has increased, and IMP-ACT shares common elements with other ACT-GLOBAL domains, allowing trial efficiency to be maximised and operational costs reduced by conducting the domain within the ACT-GLOBAL platform.
This domain will be conducted as part of the ACT-GLOBAL adaptive platform trial and has the nested domain name IMP-ACT. It is a prospective, randomized, open-label, blinded-endpoint (PROBE), adaptive, phase 3, parallel-group, controlled trial. Up to 800 participants with acute ischemic stroke due to medium vessel occlusion will be enrolled globally.
Male and female patients aged ≥18 years with acute ischemic stroke caused by a medium vessel occlusion (M2 or M3, A2 or A3, or P2 or P3 segment) confirmed on non-invasive neurovascular imaging, in whom the time from symptom onset (or last seen well) to randomization is ≤4.5 hours, with a baseline NIHSS score >5, good or moderate collateral status, and limited early ischemic change (ASPECTS ≥9), who are clinically eligible for immediate EVT and IAT and in whom the occlusion has been assessed by the attending neurointerventionalist as safely accessible by endovascular means.
Eligible patients are randomized to one of the following three arms:
Randomization occurs immediately after baseline neuroimaging (NCCT/CTA), once clinical eligibility has been determined, via a centralized, secure, concealed, real-time web-based server, thereby ensuring allocation concealment. Participants are initially allocated 1:1:1. Once 150 participants have been enrolled, response-adaptive randomization (RAR) begins and allocation probabilities are updated with accumulating trial data at each adaptive interim analysis; enrolment to usual care will match the best-performing treatment arm. A minimal sufficient balance (covariate-adaptive) algorithm balances allocation by region, age, sex, baseline stroke severity (NIHSS), occlusion location, intravenous thrombolysis, time from last known well to randomization and calendar month. Treatment is open-label; blinding of enrolling staff is neither practical nor ethical in acute stroke, and sham endovascular procedures are not feasible. Endpoint assessment is blinded.
EVT and IAT are one-time treatments administered on Day 1. The duration of an EVT procedure ranges from 20 minutes or less to 2 hours, with the majority completed within 90 minutes; IAT adds 5-10 minutes to the same angiographic procedure. Each participant is followed for one 90-day period and is hospitalized and treated according to current standard of care. At Day 30 and 90, a blinded qualified central assessor - with no access to treatment allocation, imaging information or safety data - contacts the participant for efficacy assessment. The end of the domain is defined as the date of last contact of the last participant at the Day 90 follow-up.
Duration: Recruitment is expected to take 33 months. The End of Study Activity, defined as completion of data collection following the final follow-up visit of the last patient enrolled across all participating countries, will occur approximately 9 months after enrolment of the last patient.
Visit 1 - Day 1 (Baseline): Eligibility, informed consent, demographics, medical history, frailty questionnaire, stroke-focused examination and stroke severity (NIHSS), weight, vital signs (blood pressure, heart rate, ECG), baseline imaging (non-contrast CT head and CTA arch-to-vertex, ± perfusion), baseline blood work, concomitant medications, randomization and administration of the allocated intervention (endovascular procedure or usual care - EVT, EVT + IAT or usual care), final MeVO-eTICI, and serious adverse event monitoring.
Visit 2 - Day 2 (window 18-56 hours): Neurological assessment (NIHSS at 24 hours), ambulatory status, weight, laboratory (blood) tests, concomitant medications, stroke etiology, follow-up imaging including repeat CTA (arch to vertex), and serious adverse event monitoring. Follow-up imaging is used to assess infarct volume and hemorrhagic transformation; MRI (including at minimum axial DWI, FLAIR and a hemorrhage-sensitive sequence - gradient echo or susceptibility weighted imaging) is preferred and may be supplanted by non-contrast CT if MRI is unavailable. Follow-up imaging is considered a standard-of-care imaging procedure.
Visit 3 - Day 4 (or discharge if earlier): Ambulatory status, stroke care, imaging (MR head), and continued serious adverse event monitoring. Neurovascular imaging beyond Day 2 is collected only when conducted as per standard of care.
Visit 4 - Day 30 (window -5 to +5 days): Blinded central assessment of mRS (using the Rankin Focused Assessment tool) and EQ-5D-5L. Day 30 assessments are conducted by centralized telephone or online interview by central trial personnel blinded to treatment assignment and to treatment received; conventional blinded site-based personnel may undertake the assessment if necessary.
Visit 5 - Day 90 (window -14 to +14 days): Blinded central assessment of the primary outcome (mRS using the Rankin Focused Assessment tool), EQ-5D-5L, COSMOS, ambulatory status and place of residence. Day 90 assessments are conducted by centralized telephone or online interview by central trial personnel blinded to treatment assignment and to treatment received; conventional blinded site-based personnel may undertake the assessment if necessary.
Note: only serious adverse events are collected, from enrolment up to Day 4 (inclusive); simple adverse events are not collected.
2,612 studies on the registry are indexed under Ischemic Stroke; 971 are open to participants now.
This study's planned enrollment of 800 is above the median of 120 across 1,776 interventional studies indexed under Ischemic Stroke.
Browse Ischemic Stroke studies →University of Calgary is the lead sponsor of 703 studies on the registry; 196 are open to participants now.
Of its 10 completed or terminated interventional studies of FDA-regulated products, 2 (20%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Platform inclusion criteria:
Domain (IMP-ACT) inclusion criteria:
Exclusion Criteria:
Domain (IMP-ACT) exclusion criteria:
Adaptive enrichment: Adaptive enrichment rules will allow restriction of enrolment to patients presenting ≤3 hours and/or with NIHSS >7 if interim data suggest lack of benefit among those presenting later or with baseline NIHSS ≤7.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
usual care - intravenous thrombolysis (0.18mg/kg or 0.25mg/kg of tenecteplase) if eligible, plus usual stroke unit care.
Drug: Intravenous Thrombolysis
Tools and technique left to the discretion of the operator; intra-arterial thrombolytic drugs must not be administered.
Procedure: Mechanical Endovascular Thrombectomy
microcatheter injection of tenecteplase up to 0.0625 mg/kg (maximum 6.25 mg) or alteplase up to 0.225 mg/kg (maximum 22.5 mg) over 5-10 minutes from a proximal, safe microcatheter position in the affected arterial territory, with agent selected according to local availability.
Procedure: Mechanical Endovascular Thrombectomy · Biological: Tenecteplase/Alteplase- depending upon availability at each treating centre
Mechanical endovascular thrombectomy (EVT) is a minimally invasive endovascular procedure used to remove a blood clot from an intracranial artery causing acute ischemic stroke. A catheter is advanced through the arterial system to the site of occlusion, where specialized devices such as stent retrievers and aspiration catheters are used to restore blood flow by removing the clot. EVT is an established treatment for selected patients with acute ischemic stroke and is intended to improve neurological recovery by achieving rapid reperfusion of threatened brain tissue.
Tenecteplase IV may be administered, if eligible, as part of the Control Arm.
Also known as: tenecteplase, tNKase, Metalyse,
The intervention group will receive local intra-arterial (IA) thrombolysis using either tenecteplase at a dose of 0.0625mg/kg "maximum dose of 6.25mg" or alteplase "0.225 mg/kg; maximum dose, 20mg.
Also known as: Intra-arterial thrombolysis after endovascular therapy, Thrombolytic (2 options), tNKase, Metalyse,, tPA, Activase
A change of functional dependence analyzed across the whole distribution of outcomes assessed on the modified Rankin Scale (mRS),
Modified Rankin Scale (mRS) -which scores of 0 to 1 indicate a favourable outcome without or with symptoms but no disability, scores of 2 to 5 indicate increasing levels of disability (and dependency), and a score of 6 indicates death.
Time frame: From enrollment to the Day 90 assessment - Day 90 outcomes are assessed in a blinded manner
Ordinal Modified Rankin Score at 30 days
Modified Rankin Scale (mRS) -which scores of 0 to 1 indicate a favourable outcome without or with symptoms but no disability, scores of 2 to 5 indicate increasing levels of disability (and dependency), and a score of 6 indicates death.
Time frame: telephone called performed by a " blinded assessor" between 23-37 days after randomization
24-hour National Institute of Stroke Scale Score (NIHSS)
The National Institutes of Health Stroke Scale (NIHSS) is a standardized clinical assessment used by trained healthcare professionals to measure the severity of neurological impairment caused by a stroke.It evaluates 11 areas, including level of consciousness, gaze, visual fields, facial movement, arm and leg strength, coordination, sensation, language, speech and neglect. Scores range from 0 to 42, with higher scores indicating greater neurological impairment. The NIHSS is used during the initial assessment and subsequent reassessments to document changes in neurological status and support treatment and clinical decision-making.
Time frame: From enrollment (randomization ) to 18-56 hours (Day 2)
Difference between 24 hour and baseline National Institute of Stroke Scale Score (NIHSS)
The National Institutes of Health Stroke Scale (NIHSS) is a standardized clinical assessment used by trained healthcare professionals to measure the severity of neurological impairment caused by a stroke.It evaluates 11 areas, including level of consciousness, gaze, visual fields, facial movement, arm and leg strength, coordination, sensation, language, speech and neglect. Scores range from 0 to 42, with higher scores indicating greater neurological impairment. The NIHSS is used during the initial assessment and subsequent reassessments to document changes in neurological status and support treatment and clinical decision-making.
Time frame: From enrollment (randomization) to 18-56 hours (Day 2)
Final reperfusion quality (extended Thrombolysis in Cerebral Infarction (MeVO eTICI) scale)
The thrombolysis in cerebral infarction (TICI) grading system as a tool for determining the response of thrombolytic therapy for ischemic stroke. In neurointerventional radiology it is commonly used for patients post endovascular revascularization.
Time frame: From enrollment (randomization) to post EVT procedure. Completed by the Central Core lab at 30 days after randomization
Infarct volume on 18-56-hour scan
The thrombolysis in cerebral infarction (TICI) grading system as a tool for determining the response of thrombolytic therapy for ischemic stroke. In neurointerventional radiology it is commonly used for patients post endovascular revascularization.
Time frame: Completed by the Central Core lab at 30 days after randomization
The proportion of patients with Symptomatic intracranial hemorrhage from enrolment up to Day 4
Serious Adverse events include the following events :results in death, life threatening,Requires inpatient hospitalization or prolongation of existing hospitalization,Results in persistent disability/incapacity,Is a congenital anomaly/birth defect, an important medical event that may not result in death, be life-threatening, or require hospitalization, but may jeopardize the participant and may require medical or surgical intervention to prevent an outcome listed in the SAE selection.
Time frame: From enrollment ( randomization) to Day 4
Parenchymal hemorrhage (PH-1 and PH-2)
PH-1-2:( hemorrhage grading scale) homogeneous hyperdensity occupying over 30% of the infarct zone, with significant mass effect
Time frame: From enrollment ( randomization) to Day 4
Safety Assessments of Serious Adverse Events (SAEs) from enrollment up to Day 4
Serious Adverse events include the following events :results in death, life threatening,Requires inpatient hospitalization or prolongation of existing hospitalization,Results in persistent disability/incapacity,Is a congenital anomaly/birth defect, an important medical event that may not result in death, be life-threatening, or require hospitalization, but may jeopardize the participant and may require medical or surgical intervention to prevent an outcome listed in the SAE selection.
Time frame: From enrollment ( randomization) to Day 4
The Ordinal shift of 7 levels of mRS at 90 days (mRS 5 and 6 will be collapsed in one category)
Modified Rankin Scale (mRS) -which scores of 0 to 1 indicate a favourable outcome without or with symptoms but no disability, scores of 2 to 5 indicate increasing levels of disability (and dependency), and a score of 6 indicates death.
Time frame: Done by telephone at the Day 90 assessment (Day 90 outcomes are assessed in a blinded manner)
Ambulatory status of the patient's mobility at discharge
Assessing mobility of the patient at discharge- these are the questions that are asked: If alive, can the subject walk 10 steps without assistance? (Without assistance from another person. The use of a walking aid is acceptable- yes or no.
Time frame: Completed at Day discharge or Day 4 or from randomization.
Name and location of the Place of residence at 90 days
Assessing the patient's residence at the Day 90 follow up. the information being collected is: What is the subject's place of residence at final contact? (-home, acute care hospital, repatriation to secondary hospital, inpatient rehabilitation care hospital, care facility, deceased or unknown)
Time frame: Completed at the Day 90 assessment.
Summative total length of hospital stay in the first 90-days after stroke onset
Calculating the total number of days the patient was hospitalized since their hospital admission.
Time frame: Completed at the Day 90 assessment.
Plan to share: No — Domain information and tabular trial results will be posted on the National Institutes of Health's website www.clinicaltrials.gov within one year of domain completion.
No publications or documents are linked to this record.
Start is estimated for Dec 2026; primary completion for Dec 2030, 48 months later.
Of 143 non-industry phase 3 interventional studies under Ischemic Stroke, half reached primary completion within 32 months of starting (the median), counting those still running; a quarter within 20 and three quarters within 62. This study's planned 48 months is above that.
Counting every sponsor, half of 165 studies reached it within 30 months; a quarter within 19 and three quarters within 52.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
This study is not yet recruiting, as verified in Oct 2026. You cannot join it, but the record below documents what was studied.
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