Cardiac Allograft VasculopathyPhase 3NCT04770012
AERIAL Trial: Antiplatelet Therapy in Heart Transplantation
A Phase 3 study testing aspirin and Clopidogrel in people with Cardiac Allograft Vasculopathy and Heart Transplant, run by Ottawa Heart Institute Research Corporation at 3 sites in Canada.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cardiac Allograft Vasculopathy, Heart Transplant
- What is being tested?
- aspirin and Clopidogrel
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 135 participants
- Where
- 3 sitesCanada
- Study dates
- 28 Jun 2021to Mar 2029
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Heart transplant
- Age ≥18 years
- Able to provide informed consent
Who cannot join
- 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
Show all 12Show fewer
- 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.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Heather Ross contact
Canada3 sites, 3 recruiting
- Recruiting
University of Ottawa Heart Institute
Ottawa, Ontario, K1Y 4W7
Sharon Chih
- Recruiting
Toronto General Hospital UHN
Toronto, Ontario, M5G 2C4
Heather Ross
- Recruiting
St.Pauls Hospital
Vancouver, British Columbia, V6Z 1Y6
Mustafa Toma
About this study
Official title: 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.
Read the 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.
- Conditions
- Cardiac Allograft Vasculopathy, Heart Transplant
- Being tested
- Placebo, aspirin, Clopidogrel
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
patients randomized to placebo study group will be dispensed placebo capsules to be taken daily for the duration of the treatment
aspirinDrug
patients randomized to aspirin study group will be dispensed aspirin capsules to be taken daily for the duration of the treatment
ClopidogrelDrug
Also called plavix
patients randomized to clopidogrel study group will be dispensed clopidogrel capsules to be taken daily for the duration of the treatment
| Study group | Role | What they receive |
|---|---|---|
| placebo | Placebo comparator | Not described Receives: Drug: Placebo |
| clopidogrel | Active comparator | Not described Receives: Drug: Clopidogrel |
| aspirin | Active comparator | Not described Receives: Drug: aspirin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Feasibility: Recruitment rate
Average recruitment rate of 4.5 patients per month at 3 study sites
Measured: 3 years
Feasibility: CAV event rate
2-year CAV event rate of >8%
Measured: 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%
Measured: 3 years
Feasibility: Loss to follow up rate
Loss-to-follow-up <1%
Measured: 3 years
Feasibility: Compliance to treatment
Compliance to treatment >80%
Measured: 3 years
Secondary outcomes (6)
Cardiac allograft vasculopathy
Angiographic CAV disease severity according to ISHLT CAV 0-3 grading
Measured: 1 and 2 years post transplant
Coronary intimal disease
Coronary intimal volume measured on OCT
Measured: 2 months, 1 year post transplant
Coronary endothelial function
Coronary flow reserve measured by intracoronary flow assessment
Measured: 2 months and 1 year post transplant
Coronary macrovascular function
Fractional flow reserve measured by intracoronary flow assessment
Measured: 2 months and 1 year post transplant
Coronary microvascular function
Index of microcirculatory resistance measured by intracoronary flow assessment
Measured: 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).
Measured: Baseline, 2 months and 1 year post transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2021
- Study start28 Jun 2021
- Primary completionMar 2027 (estimated)
- Study completionMar 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cardiac Allograft VasculopathyStudies of the same condition, open and under way.
- More trials run by Ottawa Heart Institute Research CorporationThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 2:2:1 randomization to placebo-control, aspirin 81 mg daily or clopidogrel 75 mg daily
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 135 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ottawa Heart Institute Research Corporation
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Responsible party
- Sponsor
- Investigators
- Sharon Chih, Principal investigator, Ottawa Heart Institute Research Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04770012
- Sponsor's protocol ID
- 2020-version 1.0
- Status last verified
- Apr 2026
- First submitted
- 25 Jan 2021
- Last updated
- 6 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Rheaume M, Aleksova N, Madsen JC, Benichou G. Chronic Rejection Series: Heart Cardiac Allograft Vasculopathy. Transplantation. 2026 Jan 1;110(1):e28-e41. doi: 10.1097/TP.0000000000005453. Epub 2025 Jul 14.
PubMed 40653611
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Initiation of Antiplatelet ThERapy In HeArt TranspLantation: AERIAL Trial
- ClinicalTrials.gov ID
- NCT04770012
- Acronym / sponsor ID
- 2020-version 1.0
- Conditions
- Cardiac Allograft Vasculopathy, Heart Transplant
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 135 participants (estimated)
- Lead sponsor
- Ottawa Heart Institute Research CorporationUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Study start
- 28 Jun 2021 (actual)
- Primary completion
- Mar 2027 (estimated)
- Study completion
- Mar 2029 (estimated)
- First posted
- 25 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
- Model description
- 2:2:1 randomization to placebo-control, aspirin 81 mg daily or clopidogrel 75 mg daily
| Arm | Type | Receives |
|---|---|---|
| placebo | Placebo comparator | Drug: Placebo |
| clopidogrel | Active comparator | Drug: Clopidogrel |
| aspirin | Active comparator | Drug: aspirin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Heart transplant
- Age ≥18 years
- Able to provide informed consent
Key exclusion criteria (12 listed)
- Allergy or known intolerance to aspirin
- Allergy or known intolerance to clopidogrel
- Intracranial hemorrhage ≤14 days
- Bleeding disorder
- Platelet count <50 x 109/L
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Placebopatients randomized to placebo study group will be dispensed placebo capsules to be taken daily for the duration of the treatment | Drug | placebo |
| aspirinpatients randomized to aspirin study group will be dispensed aspirin capsules to be taken daily for the duration of the treatment | Drug | aspirin |
| ClopidogrelAlso: plavixpatients randomized to clopidogrel study group will be dispensed clopidogrel capsules to be taken daily for the duration of the treatment | Drug | clopidogrel |
Primary outcome
Feasibility: Recruitment rate
Time frame: 3 years
Average recruitment rate of 4.5 patients per month at 3 study sites
Feasibility: CAV event rate
Time frame: 3 years
2-year CAV event rate of >8%
Feasibility: Treatment cross over rate
Time frame: 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
Time frame: 3 years
Loss-to-follow-up <1%
Feasibility: Compliance to treatment
Time frame: 3 years
Compliance to treatment >80%
6 secondary outcomes
Cardiac allograft vasculopathy
Time frame: 1 and 2 years post transplant
Coronary intimal disease
Time frame: 2 months, 1 year post transplant
Coronary endothelial function
Time frame: 2 months and 1 year post transplant
Coronary macrovascular function
Time frame: 2 months and 1 year post transplant
Coronary microvascular function
Time frame: 2 months and 1 year post transplant
Platelet Function
Time frame: Baseline, 2 months and 1 year post transplant
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2026.
- Derived from this study: PubMed 40653611Rheaume M, Aleksova N, Madsen JC, Benichou G. Chronic Rejection Series: Heart Cardiac Allograft Vasculopathy. Transplantation. 2026 Jan 1;110(1):e28-e41. doi: 10.1097/TP.0000000000005453. Epub 2025 Jul 14.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Heather Ross contact
Sharon Chih principal investigator
Ottawa Heart Institute Research Corporation
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing aspirin and Clopidogrel in people with Cardiac Allograft Vasculopathy and Heart Transplant, run by Ottawa Heart Institute Research Corporation at 3 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 6 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Sharon Chih (613-696-7000, schih@ottawaheart.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Feasibility: Recruitment rate (time frame: 3 years). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04770012, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2026.