AERIAL Trial: Antiplatelet Therapy in Heart Transplantation

Heart Transplant Clinical Trial

Official title:

Early Initiation of Antiplatelet ThERapy In HeArt TranspLantation: AERIAL Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04770012
• Other study ID #: 2020-version 1.0
• Status: Recruiting
• Phase: Phase 3
• Start date: June 28, 2021
• Est. completion date: December 2024

Study information

• Verified date: August 2023
• Source: Ottawa Heart Institute Research Corporation
• Contact: Sharon Chih
• Phone: 613-696-7000
• Email: schih[@]ottawaheart.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 135
• Est. completion date: December 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cardiac Allograft Vasculopathy
• Heart Transplant
• Vascular Diseases

Intervention

Drug:
• Placebo
patients randomized to placebo study group will be dispensed placebo capsules to be taken daily for the duration of the treatment
• aspirin
patients randomized to aspirin study group will be dispensed aspirin capsules to be taken daily for the duration of the treatment
• Clopidogrel
patients randomized to clopidogrel study group will be dispensed clopidogrel capsules to be taken daily for the duration of the treatment

Locations

Country	Name	City	State
Canada	University of Ottawa Heart Institute	Ottawa	Ontario
Canada	Toronto General Hospital UHN	Toronto	Ontario
Canada	St.Pauls Hospital	Vancouver	British Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Ottawa Heart Institute Research Corporation	Canadian Institutes of Health Research (CIHR)

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Feasibility: Recruitment rate	Average recruitment rate of 4.5 patients per month at 3 study sites	3 years
Primary	Feasibility: CAV event rate	2-year CAV event rate of >8%	3 years
Primary	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
Primary	Feasibility: Loss to follow up rate	Loss-to-follow-up <1%	3 years
Primary	Feasibility: Compliance to treatment	Compliance to treatment >80%	3 years
Secondary	Cardiac allograft vasculopathy	Angiographic CAV disease severity according to ISHLT CAV 0-3 grading	1 and 2 years post transplant
Secondary	Coronary intimal disease	Coronary intimal volume measured on OCT	2 months, 1 year post transplant
Secondary	Coronary endothelial function	Coronary flow reserve measured by intracoronary flow assessment	2 months and 1 year post transplant
Secondary	Coronary macrovascular function	Fractional flow reserve measured by intracoronary flow assessment	2 months and 1 year post transplant
Secondary	Coronary microvascular function	Index of microcirculatory resistance measured by intracoronary flow assessment	2 months and 1 year post transplant
Secondary	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