AERIAL Trial: Antiplatelet Therapy in Heart Transplantation

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Early Initiation of Antiplatelet ThERapy In HeArt TranspLantation: AERIAL Trial

Conditions
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Cardiac Allograft Vasculopathy, Heart Transplant

Intervention / Treatment
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* Drug: Placebo
* Drug: aspirin
* Drug: Clopidogrel


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 2:2:1 randomization to placebo-control, aspirin 81 mg daily or clopidogrel 75 mg daily
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: placebo<br> | Drug: Placebo<br>* patients randomized to placebo study group will be dispensed placebo capsules to be taken daily for the duration of the treatment<br>|
| Active Comparator: clopidogrel<br> | Drug: Clopidogrel<br>* patients randomized to clopidogrel study group will be dispensed clopidogrel capsules to be taken daily for the duration of the treatment<br>* Other names: plavix;|
| Active Comparator: aspirin<br> | Drug: aspirin<br>* patients randomized to aspirin study group will be dispensed aspirin capsules to be taken daily for the duration of the treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility: Recruitment rate | Average recruitment rate of 4.5 patients per month at 3 study sites | 3 years | 
| Feasibility: CAV event rate | 2-year CAV event rate of >8% | 3 years | 
| Feasibility: Treatment cross over rate | Crossover from aspirin to placebo <2%, clopidogrel to placebo <2%, placebo to aspirin <4%, placebo to clopidogrel <1% | 3 years | 
| Feasibility: Loss to follow up rate | Loss-to-follow-up <1% | 3 years | 
| Feasibility: Compliance to treatment | Compliance to treatment >80% | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiac allograft vasculopathy | Angiographic CAV disease severity according to ISHLT CAV 0-3 grading | 1 and 2 years post transplant | 
| Coronary intimal disease | Coronary intimal volume measured on OCT | 2 months, 1 year post transplant | 
| Coronary endothelial function | Coronary flow reserve measured by intracoronary flow assessment | 2 months and 1 year post transplant | 
| Coronary macrovascular function | Fractional flow reserve measured by intracoronary flow assessment | 2 months and 1 year post transplant | 
| Coronary microvascular function | Index of microcirculatory resistance measured by intracoronary flow assessment | 2 months and 1 year post transplant | 
| Platelet Function | Assessment of response to antiplatelet therapy using Enzyme-Linked Immunosorbent Assays (ELISA) for thromboxane B2 and Vasodilator Stimulated Phosphoprotein (VASP). | Baseline, 2 months and 1 year post transplant |