A Phase 2/3 interventional study of Topical epinephrine and Placebos in Lung Transplant; Complications, Mechanical, Lung Transplant; Complications and Bleeding, sponsored by University of Maryland, Baltimore. Completed at 2 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-08-28.
Sponsored by University of Maryland, Baltimore · Phase 2/3, Interventional, and Prevention
Bleeding poses potential for significant complication after transbronchial lung biopsies. The investigators hypothesize that prophylactic intrabronchial instillation of topical epinephrine will reduce the likelihood of bleeding. The investigators plan a double-blind, placebo controlled trial to evaluate this hypothesis.
The role of prophylactic topical epinephrine in improving hemostasis and prevention of clinically-significant pulmonary hemorrhage has never been studied formally in the past, despite its common use by pulmonologists performing bronchoscopic TBLB. Lung transplant recipients undergo multiple bronchoscopies and TBLBs for surveillance and evaluation of ACR as well as lung infection, especially during the first year post-transplantation. This population may have a predilection to TBLB-related bleeding and may benefit from measures to reduce the frequency and magnitude of this relatively common complication.
In the PROPHET trial, the investigators intend to assess the degree of biopsy-related bleeding, measures taken to control bleeding, and potential effects of bleeding on completion of the intended procedure in 50 bronchoscopy procedures performed on single and double lung transplant recipients, randomized to prophylactic topical epinephrine versus placebo (normal saline). The study participant, physician performing the TBLB, and independent observer reviewing the procedure recording will all be blinded to the randomization. Further use of measures to control bleeding that occurs during the procedure as well as the decision to complete the procedure as planned or to abort it prematurely will be left to the discretion of the performer. In this way, the investigators aim to elucidate a potential role of topical epinephrine in the prevention of TBLB-related airway bleeding in lung transplant recipients and assess whether the dose and volume of instillation used in the investigators' institution comprises an effective means to prevent hemorrhagic complications of TBLB.
HYPOTHESIS
The investigators hypothesize that prophylactic instillation of topical epinephrine prior to performance of TBLB will decrease the frequency and extent of biopsy-related hemorrhage as well as result in fewer procedures being aborted earlier than intended due to bleeding complications as well as shorter overall procedure time due to the preventive effect on bleeding. Concomitantly, the investigators hypothesize that the instillation of topical epinephrine will not be associated with a serious adverse event profile in comparison to placebo.
SPECIFIC AIMS
In this randomized-controlled double blind placebo controlled clinical trial post-lung transplant patients scheduled to receive bronchoscopy with TBLB as part of their routine standard of care will be randomized to receive a fixed dose and volume of topical endobronchial epinephrine versus matching volume of placebo which will be instilled into the target biopsy airway prior to performance of TBLB. This study will specifically aim at providing the following information:
Aim 1: Demonstrate the feasibility of assessments of bleeding related to TBLB, including:
Aim 2: Evaluate the hypothesis that prophylactic administration of topical epinephrine results in reductions in TBLB-related hemorrhage in lung transplant recipients, including:
Aim 3: Evaluate the hypothesis that prophylactic administration of topical epinephrine affects the overall efficiency of bronchoscopy with TBLB performance, including:
Aim 4: Explore the hypothesis that instillation of our prespecified dose and volume of topical epinephrine into the target biopsy airway is not associated with an adverse event profile that is significantly different from placebo, including:
37 studies on the registry are indexed under Hemoptysis; 6 are open to participants now.
This study's enrollment of 66 is close to the median of 73 across 20 interventional studies indexed under Hemoptysis.
Browse Hemoptysis studies →University of Maryland, Baltimore is the lead sponsor of 700 studies on the registry; 132 are open to participants now.
Of its 92 completed or terminated interventional studies of FDA-regulated products, 66 (72%) have results posted.
Compared within Hemoptysis, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Hemorrhage. The counts are of registry records indexed under each term, refreshed daily. How we classify →
Inclusion Criteria:
Exclusion Criteria:
Exclusion criteria for TBLB:
Exclusion criteria for application of topical epinephrine:
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.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
INR, PT and aPTT (clotting tests)
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Study participants who meet inclusion and exclusion criteria and allocated to this arm will be randomized to receive prophylactic endobronchial topical epinephrine in a blinded manner prior to performance of transbronchial lung biopsy.
Drug: Topical epinephrine
Study participants who meet inclusion and exclusion criteria and allocated to this arm will be randomized to receive prophylactic endobronchial topical placebo in the form of normal saline in a blinded manner prior to performance of transbronchial lung biopsy.
Drug: Placebos
Prophylactic topical epinephrine
Topical placebo (normal saline)
Also known as: Placebo
Intra-procedural Hemorrhage Grading by the Performing Bronchoscopist
Intra-procedural hemorrhage will be graded by the performing bronchoscopist according to the following scale: 1. No hemorrhage. 2. Mild hemorrhage - Any bleeding originating from the biopsy target airway requiring wedging of the bronchoscope or "in and out" motion in order to achieve hemostasis. 3. Moderate hemorrhage - Any bleeding originating from the biopsy target airway requiring in addition to maneuvering the bronchoscope application of iced saline or topical epinephrine or placing the patient with the bleeding lung in the dependent position. 4. Severe hemorrhage - Any bleeding originating from the biopsy target airway requiring, in addition to the above-mentioned maneuvers, early termination of the procedure or necessitating application of balloon tamponade, endotracheal intubation, application of a bronchial blocker, or use of other invasive measures to achieve hemostasis, such as bronchial artery embolization or surgical intervention.
Time frame: This outcome will be analyzed at the time of procedure performance and up to 48 hours following the procedure.
Eligible patients undergoing bronchoscopy with transbronchial biopsies after lung transplantation were offered participation in the study.
| Milestone | Prophylactic Topical Epinephrine | Placebo |
|---|---|---|
| Started | 33 | 33 |
| Completed | 33 | 33 |
| Not completed | 0 | 0 |
Intra-procedural hemorrhage will be graded by the performing bronchoscopist according to the following scale: 1. No hemorrhage. 2. Mild hemorrhage - Any bleeding originating from the biopsy target airway requiring wedging of the bronchoscope or "in and out" motion in order to achieve hemostasis. 3. Moderate hemorrhage - Any bleeding originating from the biopsy target airway requiring in addition to maneuvering the bronchoscope application of iced saline or topical epinephrine or placing the patient with the bleeding lung in the dependent position. 4. Severe hemorrhage - Any bleeding originating from the biopsy target airway requiring, in addition to the above-mentioned maneuvers, early termination of the procedure or necessitating application of balloon tamponade, endotracheal intubation, application of a bronchial blocker, or use of other invasive measures to achieve hemostasis, such as bronchial artery embolization or surgical intervention.
| Procedures | Prophylactic Topical Epinephrine | Placebo |
|---|---|---|
| Severe or very severe hemorrhage | 4 | 13 |
| Moderate, severe, or very severe hemorrhage | 11 | 24 |
| Unblinded administration of epinephrine for bleeding | 8 | 20 |
| Early termination of the procedure due to bleeding | 4 | 13 |
Collected over 48 hours. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Prophylactic Topical Epinephrine | 0/33 (0%) | 4/33 (12.1%) | 16/33 (48.5%) |
| Placebo | 0/33 (0%) | 4/33 (12.1%) | 18/33 (54.5%) |
| Event | Prophylactic Topical Epinephrine | Placebo |
|---|---|---|
| Hypoxemic respiratory failureRespiratory, thoracic and mediastinal disorders | 2/33 | 3/33 |
| PneumothoraxRespiratory, thoracic and mediastinal disorders | 2/33 | 1/33 |
| Event | Prophylactic Topical Epinephrine | Placebo |
|---|---|---|
| Drop in BP >20 from baselineCardiac disorders | 16/33 | 18/33 |
Study consisted of 100 procedures performed on 66 participants as participants were permitted to participate more than once.
| Age, Continuous(years) | Prophylactic Topical Epinephrine | Placebo | Total |
|---|---|---|---|
| Median | 62 (55 to 68) | 64 (56 to 68) | 63.5 (56 to 68) |
| Sex: Female, Male(Participants) | Prophylactic Topical Epinephrine | Placebo | Total |
|---|---|---|---|
| Female | 11 | 12 | 23 |
| Male | 22 | 21 | 43 |
| Race/Ethnicity, Customized(Participants) | Prophylactic Topical Epinephrine | Placebo | Total |
|---|---|---|---|
| Race / Ethnicity — African American | 10 | 12 | 22 |
| Race / Ethnicity — Latino | 1 | 4 | 5 |
| Race / Ethnicity — Caucasian | 22 | 17 | 39 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No
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Studies of the drug tested here: Epinephrine
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