AERIAL Trial: Antiplatelet Therapy in Heart Transplantation

Phase 3

Recruiting

• Conditions: Cardiac Allograft Vasculopathy; Heart Transplant
• Interventions: Drug: Placebo; Drug: Clopidogrel; Drug: aspirin

• Registration Number: NCT04770012
• Lead Sponsor: Ottawa Heart Institute Research Corporation

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.

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 Timeline

• Study First Submitted: 2021-01-25
• Study First Submitted QC: 2021-02-22
• Study First Posted: 2021-02-25
• Study Start: 2021-06-28
• Status Verified: 2024-07
• Last Update Submitted: 2025-03-28
• Last Update Posted: 2025-04-03
• Primary Completion: 2027-03
• Study Completion: 2029-03

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 135

Inclusion Criteria

1. Heart transplant
2. Age ≥18 years
3. Able to provide informed consent

Exclusion Criteria

1. Allergy or known intolerance to aspirin
2. Allergy or known intolerance to clopidogrel
3. Intracranial hemorrhage ≤14 days
4. Bleeding disorder
5. Platelet count <50 x 109/L
6. History of aspirin related gastrointestinal bleeding or ulcers
7. Non-cardiac indication for antiplatelet therapy
8. Anticoagulation >3 months
9. Allergy to iodinated contrast
10. Unable to undergo coronary angiography due to glomerular filtration rate ≤30 mL/min/1.73 m2 for non-dialysis patients
11. Unable to undergo coronary angiography due to unsuitable vascular access
12. Combined solid organ transplantation.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
placebo	Placebo	-
clopidogrel	Clopidogrel	-
aspirin	aspirin	-

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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).

Trial Locations

Locations (3)

University of Ottawa Heart Institute; 🇨🇦 Ottawa, Ontario, Canada

Toronto General Hospital UHN; 🇨🇦 Toronto, Ontario, Canada

St.Pauls Hospital; 🇨🇦 Vancouver, British Columbia, Canada