AERIAL Trial: Antiplatelet Therapy in Heart Transplantation
Study Details
Study Description
Brief Summary
Cardiac allograft vasculopathy is a common complication affecting heart transplant patients. This condition causes narrowing of the heart arteries leading to graft dysfunction. The research team is investigating whether early antiplatelet therapy post heart transplant can prevent the development of CAV. This study will determine the feasibility of a large multicenter randomized placebo-controlled trial to answer this question.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
Heart transplant patients who fulfill selection criteria will undergo baseline clinical evaluation and data collection. Participants will be randomized to either placebo, aspirin or clopidogrel to be taken daily for the duration of the study. Patients will undergo invasive coronary studies (angiography, optical coherence tomography and intracoronary flow) and platelet function testing at 2 and 12 months post heart transplant. In addition, angiography will be performed at 24 months post heart transplant and thereafter according to institutional protocol. The primary analysis will determine the feasibility of conducting a large multicenter randomized placebo controlled trial by assessing recruitment rates, event rates, treatment crossovers and loss to follow-up. Secondary analyses will include assessing the effect of antiplatelet treatment on angiographic CAV, coronary intimal disease on optical coherence tomography, coronary macrovascular and microvascular function by intracoronary flow measures, and platelet function.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: placebo
|
Drug: Placebo
patients randomized to placebo study group will be dispensed placebo capsules to be taken daily for the duration of the treatment
|
| Active Comparator: clopidogrel
|
Drug: Clopidogrel
patients randomized to clopidogrel study group will be dispensed clopidogrel capsules to be taken daily for the duration of the treatment
Other Names:
|
| Active Comparator: aspirin
|
Drug: aspirin
patients randomized to aspirin study group will be dispensed aspirin capsules to be taken daily for the duration of the treatment
|
Outcome Measures
Primary Outcome Measures
- Feasibility: Recruitment rate [3 years]
Average recruitment rate of 4.5 patients per month at 3 study sites
- Feasibility: CAV event rate [3 years]
2-year CAV event rate of >8%
- Feasibility: Treatment cross over rate [3 years]
Crossover from aspirin to placebo <2%, clopidogrel to placebo <2%, placebo to aspirin <4%, placebo to clopidogrel <1%
- Feasibility: Loss to follow up rate [3 years]
Loss-to-follow-up <1%
- Feasibility: Compliance to treatment [3 years]
Compliance to treatment >80%
Secondary Outcome Measures
- Cardiac allograft vasculopathy [1 and 2 years post transplant]
Angiographic CAV disease severity according to ISHLT CAV 0-3 grading
- Coronary intimal disease [2 months, 1 year post transplant]
Coronary intimal volume measured on OCT
- Coronary endothelial function [2 months and 1 year post transplant]
Coronary flow reserve measured by intracoronary flow assessment
- Coronary macrovascular function [2 months and 1 year post transplant]
Fractional flow reserve measured by intracoronary flow assessment
- Coronary microvascular function [2 months and 1 year post transplant]
Index of microcirculatory resistance measured by intracoronary flow assessment
- Platelet Function [Baseline, 2 months and 1 year post transplant]
Assessment of response to antiplatelet therapy using Enzyme-Linked Immunosorbent Assays (ELISA) for thromboxane B2 and Vasodilator Stimulated Phosphoprotein (VASP).
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Heart transplant
-
Age ≥18 years
-
Able to provide informed consent
Exclusion Criteria:
-
Allergy or known intolerance to aspirin
-
Allergy or known intolerance to clopidogrel
-
Intracranial hemorrhage ≤14 days
-
Bleeding disorder
-
Platelet count <50 x 109/L
-
History of aspirin related gastrointestinal bleeding or ulcers
-
Non-cardiac indication for antiplatelet therapy
-
Anticoagulation >3 months
-
Allergy to iodinated contrast
-
Unable to undergo coronary angiography due to glomerular filtration rate ≤30 mL/min/1.73 m2 for non-dialysis patients
-
Unable to undergo coronary angiography due to unsuitable vascular access
-
Combined solid organ transplantation.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | St.Pauls Hospital | Vancouver | British Columbia | Canada | V6Z 1Y6 |
| 2 | University of Ottawa Heart Institute | Ottawa | Ontario | Canada | K1Y 4W7 |
| 3 | Toronto General Hospital UHN | Toronto | Ontario | Canada | M5G 2C4 |
Sponsors and Collaborators
- Ottawa Heart Institute Research Corporation
- Canadian Institutes of Health Research (CIHR)
Investigators
- Principal Investigator: Sharon Chih, Ottawa Heart Institute Research Corporation
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2020-version 1.0