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AERIAL Trial: Antiplatelet Therapy in Heart Transplantation

Primary Purpose

Cardiac Allograft Vasculopathy, Heart Transplant

Status
Recruiting
Phase
Phase 3
Locations
Canada
Study Type
Interventional
Intervention
Placebo
aspirin
Clopidogrel
Sponsored by
Ottawa Heart Institute Research Corporation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cardiac Allograft Vasculopathy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • St.Pauls HospitalRecruiting
  • University of Ottawa Heart InstituteRecruiting
  • Toronto General Hospital UHNRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Active Comparator

Active Comparator

Arm Label

placebo

clopidogrel

aspirin

Arm Description

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Cardiac allograft vasculopathy
Angiographic CAV disease severity according to ISHLT CAV 0-3 grading
Coronary intimal disease
Coronary intimal volume measured on OCT
Coronary endothelial function
Coronary flow reserve measured by intracoronary flow assessment
Coronary macrovascular function
Fractional flow reserve measured by intracoronary flow assessment
Coronary microvascular function
Index of microcirculatory resistance measured by intracoronary flow assessment
Platelet Function
Assessment of response to antiplatelet therapy using Enzyme-Linked Immunosorbent Assays (ELISA) for thromboxane B2 and Vasodilator Stimulated Phosphoprotein (VASP).

Full Information

First Posted
January 25, 2021
Last Updated
August 11, 2023
Sponsor
Ottawa Heart Institute Research Corporation
Collaborators
Canadian Institutes of Health Research (CIHR)
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1. Study Identification

Unique Protocol Identification Number
NCT04770012
Brief Title
AERIAL Trial: Antiplatelet Therapy in Heart Transplantation
Official Title
Early Initiation of Antiplatelet ThERapy In HeArt TranspLantation: AERIAL Trial
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 28, 2021 (Actual)
Primary Completion Date
June 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ottawa Heart Institute Research Corporation
Collaborators
Canadian Institutes of Health Research (CIHR)

4. Oversight

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
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cardiac Allograft Vasculopathy, Heart Transplant

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
2:2:1 randomization to placebo-control, aspirin 81 mg daily or clopidogrel 75 mg daily
Masking
ParticipantCare ProviderInvestigator
Masking Description
Patients, clinical care providers and research staff will be blinded to treatment allocation.
Allocation
Randomized
Enrollment
135 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
placebo
Arm Type
Placebo Comparator
Arm Title
clopidogrel
Arm Type
Active Comparator
Arm Title
aspirin
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
patients randomized to placebo study group will be dispensed placebo capsules to be taken daily for the duration of the treatment
Intervention Type
Drug
Intervention Name(s)
aspirin
Intervention Description
patients randomized to aspirin study group will be dispensed aspirin capsules to be taken daily for the duration of the treatment
Intervention Type
Drug
Intervention Name(s)
Clopidogrel
Other Intervention Name(s)
plavix
Intervention Description
patients randomized to clopidogrel study group will be dispensed clopidogrel capsules to be taken daily for the duration of the treatment
Primary Outcome Measure Information:
Title
Feasibility: Recruitment rate
Description
Average recruitment rate of 4.5 patients per month at 3 study sites
Time Frame
3 years
Title
Feasibility: CAV event rate
Description
2-year CAV event rate of >8%
Time Frame
3 years
Title
Feasibility: Treatment cross over rate
Description
Crossover from aspirin to placebo <2%, clopidogrel to placebo <2%, placebo to aspirin <4%, placebo to clopidogrel <1%
Time Frame
3 years
Title
Feasibility: Loss to follow up rate
Description
Loss-to-follow-up <1%
Time Frame
3 years
Title
Feasibility: Compliance to treatment
Description
Compliance to treatment >80%
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Cardiac allograft vasculopathy
Description
Angiographic CAV disease severity according to ISHLT CAV 0-3 grading
Time Frame
1 and 2 years post transplant
Title
Coronary intimal disease
Description
Coronary intimal volume measured on OCT
Time Frame
2 months, 1 year post transplant
Title
Coronary endothelial function
Description
Coronary flow reserve measured by intracoronary flow assessment
Time Frame
2 months and 1 year post transplant
Title
Coronary macrovascular function
Description
Fractional flow reserve measured by intracoronary flow assessment
Time Frame
2 months and 1 year post transplant
Title
Coronary microvascular function
Description
Index of microcirculatory resistance measured by intracoronary flow assessment
Time Frame
2 months and 1 year post transplant
Title
Platelet Function
Description
Assessment of response to antiplatelet therapy using Enzyme-Linked Immunosorbent Assays (ELISA) for thromboxane B2 and Vasodilator Stimulated Phosphoprotein (VASP).
Time Frame
Baseline, 2 months and 1 year post transplant

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sharon Chih
Phone
613-696-7000
Email
schih@ottawaheart.ca
First Name & Middle Initial & Last Name or Official Title & Degree
Heather Ross
Email
heather.ross@uhn.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sharon Chih
Organizational Affiliation
Ottawa Heart Institute Research Corporation
Official's Role
Principal Investigator
Facility Information:
Facility Name
St.Pauls Hospital
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6Z 1Y6
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mustafa Toma
Facility Name
University of Ottawa Heart Institute
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1Y 4W7
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sharon Chih
Facility Name
Toronto General Hospital UHN
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2C4
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Heather Ross

12. IPD Sharing Statement

Learn more about this trial

AERIAL Trial: Antiplatelet Therapy in Heart Transplantation

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