Antiplatelet Therapy for Cardiac Vasculopathy Post-Heart Transplant

Recruiting at 2 trial locations

Overseen By Heather Ross

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Ottawa Heart Institute Research Corporation

Must not be taking: Anticoagulants

Disqualifiers: Bleeding disorder, Low platelet count, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 3 years

135 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether early antiplatelet therapy, using drugs like aspirin and clopidogrel, can prevent cardiac allograft vasculopathy, a condition that narrows heart arteries and affects heart transplant patients. The trial includes different groups to compare the effects of aspirin, clopidogrel, and a placebo (a harmless pill with no active drug). Heart transplant recipients who can safely take these medications may qualify for the study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on antiplatelet therapy for non-cardiac reasons, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that aspirin is generally safe for heart transplant patients. One study found that aspirin might reduce the risk of cardiac allograft vasculopathy (CAV), a condition affecting the heart's arteries. Notably, this study did not report an increase in stomach bleeding, a common concern with aspirin use.

Clopidogrel, another drug under investigation, helps prevent blood clots like aspirin. Although specific safety information for clopidogrel in heart transplant patients is limited, it is commonly used for other heart conditions, suggesting it is usually well-tolerated. However, further research is needed to confirm its safety for heart transplant patients.

Both treatments are under study for their potential to prevent CAV after heart transplants. It is essential to consult a doctor to understand the implications of participating in a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments, aspirin and clopidogrel, because they may offer improved options for managing cardiac vasculopathy after a heart transplant. Unlike typical treatments that often focus on traditional anti-rejection medications, these antiplatelet therapies work by preventing blood clots, thereby potentially reducing the risk of blood vessel complications. Aspirin and clopidogrel each have unique mechanisms: aspirin inhibits platelet aggregation, while clopidogrel blocks platelet activation. This dual approach could enhance the long-term success of heart transplants by offering more comprehensive protection against vascular issues.

What evidence suggests that this trial's treatments could be effective for cardiac vasculopathy post-heart transplant?

Research has shown that taking aspirin soon after a heart transplant might help lower the risk of cardiac allograft vasculopathy (CAV), a condition where the heart's arteries narrow. One study found that patients who started aspirin early had fewer cases of moderate to severe CAV, particularly if they also experienced episodes of organ rejection. Over a follow-up period of 6.7 years, those who took aspirin early had a lower risk of dying from any cause. In this trial, some participants will receive aspirin to assess its effectiveness.

For clopidogrel, animal studies suggest it can prevent transplant arteriosclerosis, a similar issue with blood vessels in transplants. However, researchers are still studying its effects on heart transplant patients to understand its impact. This trial will also include a group receiving clopidogrel to evaluate its potential benefits. Both aspirin and clopidogrel prevent blood cells from sticking together, which can block arteries. ^{1 6 7 8 9}

Who Is on the Research Team?

Sharon Chih

Principal Investigator

Ottawa Heart Institute Research Corporation

Are You a Good Fit for This Trial?

The AERIAL Trial is for adults who've had a heart transplant and can give informed consent. It's not for those with allergies to aspirin or clopidogrel, recent intracranial hemorrhage, bleeding disorders, very low platelet counts, past aspirin-related stomach issues, need for antiplatelets due to other conditions, allergy to iodine contrast agents, or poor kidney function preventing coronary angiography.

Inclusion Criteria

I have had a heart transplant.

Able to provide informed consent

Exclusion Criteria

I have a bleeding disorder.

I cannot have a heart artery test due to low kidney function and I'm not on dialysis.

I have been on blood thinners for more than 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Evaluation

Baseline clinical evaluation and data collection for heart transplant patients

1 week

Treatment

Participants are randomized to receive either placebo, aspirin, or clopidogrel daily

3 years

Visits at 2 months, 1 year, and 2 years post-transplant for invasive coronary studies and platelet function testing

Follow-up

Participants are monitored for safety and effectiveness after treatment, including angiography at 24 months and according to institutional protocol

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Aspirin
• Clopidogrel
• Placebo

Trial Overview This trial tests if early use of antiplatelet drugs like aspirin or clopidogrel can prevent artery narrowing after heart transplants compared to a placebo. The goal is to see if this approach could work in a larger study across multiple centers.

How Is the Trial Designed?

Group I: aspirin Active Control 1 Intervention

Group II: clopidogrel Active Control 1 Intervention

Group III: placebo Placebo Group 1 Intervention

Aspirin is already approved in European Union, United States, Canada, China for the following indications:

Approved in European Union as Aspirin for:

• Pain relief
• Fever reduction
• Inflammation
• Cardiovascular disease prevention
• Preeclampsia prevention

Approved in United States as Aspirin for:

• Pain relief
• Fever reduction
• Inflammation
• Cardiovascular disease prevention
• Preeclampsia prevention

Approved in Canada as Aspirin for:

• Pain relief
• Fever reduction
• Inflammation
• Cardiovascular disease prevention
• Preeclampsia prevention

Approved in China as Aspirin for:

• Pain relief
• Fever reduction
• Inflammation
• Cardiovascular disease prevention

Who Is Running the Clinical Trial?

Ottawa Heart Institute Research Corporation

Lead Sponsor

Trials

200

Recruited

95,800+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Published Research Related to This Trial

Heart transplant recipients showed significantly increased platelet hyperaggregation compared to healthy individuals and nontransplant coronary patients, indicating a heightened risk for blood clotting issues.

Platelets from heart transplant recipients were resistant to the effects of aspirin, the main antiplatelet medication, which may contribute to the higher incidence of myocardial infarction in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased platelet aggregation after heart transplantation: influence of aspirin. de Lorgeril, M., Dureau, G., Boissonnat, P., et al.[2013]

In a study of 3436 patients admitted for lower gastrointestinal bleeding (LGIB), it was found that while dual antiplatelet therapy (aspirin and clopidogrel) and other anticoagulants were common, they did not significantly increase the risk of severe LGIB requiring major interventions.

Among the 511 patients with confirmed LGIB, only 61 were on dual or multiple antithrombotic therapies, indicating that while these therapies may raise overall bleeding risk, they do not lead to more severe bleeding events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual Antiplatelet Therapy and the Severity Risk of Lower Intestinal Bleeding. Carlin, N., Asslo, F., Sison, R., et al.[2020]

Triple antithrombotic therapy, which includes acetylsalicylic acid, clopidogrel, and warfarin, is commonly used after coronary stent implantation to lower the risk of thrombosis, but it significantly increases the risk of bleeding complications.

To minimize bleeding risks while maintaining efficacy, strategies such as careful monitoring of INR, limiting the duration of triple therapy, and using radial access with bare metal stents are recommended.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Warfarin combined with blood platelet inhibition]. Vik-Mo, H.[2013]

Heart transplant patients with cardiac allograft vasculopathy (CAV) showed significantly higher platelet aggregation compared to both healthy controls and heart transplant patients without CAV, indicating a potential risk factor for complications.

Low-dose aspirin treatment reduced platelet aggregation in heart transplant patients, but those with CAV still exhibited higher levels of aggregation on aspirin compared to those without CAV, suggesting that aspirin alone may not be sufficient for effective platelet inhibition in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Platelet aggregation and response to aspirin therapy in cardiac allograft vasculopathy. Bjerre, KP., Clemmensen, TS., Berg, K., et al.[2021]

In a study of 529 heart transplant recipients, early use of aspirin (ASA) within the first year significantly reduced the progression of cardiac allograft vasculopathy (CAV), as indicated by lower plaque volume and plaque index.

Patients who started ASA early also experienced lower all-cause mortality and no cardiac deaths, suggesting that early ASA treatment may improve survival and reduce the risk of graft dysfunction after heart transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of Aspirin Treatment With Cardiac Allograft Vasculopathy Progression and Adverse Outcomes After Heart Transplantation. Asleh, R., Briasoulis, A., Smith, B., et al.[2021]

In a study of 321 patients with HeartMate 3 LVADs, both usual-dose (325 mg) and low-dose (81 mg) aspirin showed similar rates of survival free from hemocompatibility-related adverse events (HRAEs) after 2 years, indicating that lower doses may be just as effective.

There were no significant differences in rates of bleeding or thrombotic events between the usual-dose and low-dose groups, suggesting that the optimal aspirin dose for patients with HM3 LVADs may not need to be high.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of aspirin dose on hemocompatibility-related outcomes with a magnetically levitated left ventricular assist device: An analysis from the MOMENTUM 3 study. Saeed, O., Colombo, PC., Mehra, MR., et al.[2021]

Aspirin remains the preferred antiplatelet agent for most patients with atherothrombotic disease due to its established efficacy, safety, and cost-effectiveness in preventing recurrent vascular events.

Clopidogrel can be beneficial for patients with peripheral arterial disease or those who cannot tolerate aspirin, providing an alternative treatment option when aspirin is ineffective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic benefit. Aspirin revisited in light of the introduction of clopidogrel. Gorelick, PB., Born, GV., D'Agostino, RB., et al.[2022]

In a study of 197 patients undergoing coronary artery bypass grafting (CABG), both clopidogrel alone and the combination of clopidogrel with aspirin maintained high graft patency rates at 1 and 12 months post-surgery.

There were no significant differences in graft patency between the two treatment groups, indicating that either antiplatelet therapy is effective for preventing graft failure after CABG.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clopidogrel and aspirin versus clopidogrel alone on graft patency after coronary artery bypass grafting. Gao, C., Ren, C., Li, D., et al.[2022]

Clopidogrel, when used alongside aspirin, is effective and safe as an antiplatelet agent in patients undergoing coronary stenting, including those with transplanted hearts.

In a reported case, direct coronary stenting in a transplanted heart was successful, with preserved vessel patency and no signs of restenosis observed during a 4-month follow-up angiography.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clopidogrel as an antiplatelet agent in transplant heart coronary stenting. Mahadevan, VS., Khan, MM., Adgey, JA.[2019]

In a study of 120 heart transplant patients, early use of aspirin (ASA) for more than 6 months was linked to significantly lower rates of moderate to severe cardiac allograft vasculopathy (CAV) in patients who experienced acute cellular rejection or antibody-mediated rejection.

However, ASA use did not show a protective effect against CAV in patients without any rejection episodes, suggesting that its benefits may be most pronounced in those facing rejection after transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early aspirin use, allograft rejection, and cardiac allograft vasculopathy in heart transplantation. Bergmark, BA., Zelniker, TA., Kim, M., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10939248/

Acetylsalicylic acid use and development of cardiac ... This study showed a benefit of early ASA use after HTx on lipid plaque progression. However, ASA use did not have any impact on the progression of other OCT ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1071916421000476

Association of Aspirin Treatment With Cardiac Allograft ... Over a 6.7-year follow-up, all-cause mortality was lower with early ASA compared with late or no ASA use (P < .001). No cardiac deaths were observed in the ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34254366/

Early aspirin use, allograft rejection, and cardiac ... Conclusions: Early ASA use after OHT was associated with lower rates of moderate to severe CAV only in those patients with episodes of allograft rejection.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1053249822021088

A pediatric heart transplant society analysis Adult literature suggests that aspirin (ASA) use in the early post-HTx period may reduce the risk of CAV. This study aimed to determine the impact of early ASA ...

5. researchgate.net researchgate.net/publication/315851438_Early_Aspirin_Initiation_Following_Heart_Transplantation_Decreases_the_Risk_of_Allograft_Vasculopathy_During_Long-Term_Follow-Up

Early Aspirin Initiation Following Heart Transplantation ... Data in adult heart transplant (HTx) recipients suggests that aspirin (ASA) use may reduce the risk of CAV. However, there are limited pediatric ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1053249821003910

Aspirin Use and the Development of Cardiac Allograft ... Data in adult heart transplant (HTx) recipients suggests that aspirin (ASA) use may reduce the risk of CAV. However, there are limited pediatric data on this ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8029762/

Association between aspirin use and cardiovascular ... Our study showed that aspirin use associates with lower all‐cause mortality and no increase in GI bleeding in patients with normal renal ...

8. jacc.org jacc.org/doi/10.1016/j.jchf.2025.01.017

Concomitant Surgical Procedures and Aspirin Avoidance ... Our findings support the safety and efficacy of aspirin avoidance from the antithrombotic regimen in HM3 LVAD patients undergoing concomitant surgical ...

9. myast.org myast.org/uploads/files/general/Ch.-8-Additional-Organ-Specific-Considerations_44.11.23.pdf

8. Additional organ-specific considerations Early aspirin use was associated with a statistically significant reduction in CAV risk of 84%. Andreassen AK, et al. (2016). Everolimus initiation with early ...