AERIAL Trial: Antiplatelet Therapy in Heart Transplantation

Early Initiation of Antiplatelet ThERapy In HeArt TranspLantation: AERIAL Trial

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.

Study Overview

• Status: Recruiting
• Conditions: Cardiac Allograft Vasculopathy; Heart Transplant
• Intervention / Treatment: Drug: Placebo; Drug: Clopidogrel; Drug: aspirin

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 Type: Interventional
• Enrollment (Estimated): 135
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Sharon Chih; Phone Number: 613-696-7000; Email: schih@ottawaheart.ca
• Study Contact Backup: Name: Heather Ross; Email: heather.ross@uhn.ca

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • Recruiting
      • St.Pauls Hospital
      • Contact: Mustafa Toma
  • Ontario
    • Ottawa, Ontario, Canada, K1Y 4W7
      • Recruiting
      • University of Ottawa Heart Institute
      • Contact: Sharon Chih
    • Toronto, Ontario, Canada, M5G 2C4
      • Recruiting
      • Toronto General Hospital UHN
      • Contact: Heather Ross

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / 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: plavix
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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Ottawa Heart Institute Research Corporation
• Collaborators: Canadian Institutes of Health Research (CIHR)
• Investigators: Principal Investigator: Sharon Chih, Ottawa Heart Institute Research Corporation

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2021
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: January 25, 2021
• First Submitted That Met QC Criteria: February 22, 2021
• First Posted (Actual): February 25, 2021

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: August 11, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Aspirin; Clopidogrel
• Other Study ID Numbers: 2020-version 1.0

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No