Clopidogrel + Aspirin for Stroke

(CoPrime Trial)

Overseen By Emily Sugars

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Alberta

Must be taking: Antiplatelets

Must not be taking: Anticoagulants

Disqualifiers: Bleeding disorders, Recent hemorrhage, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 21 days

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two medications, aspirin and clopidogrel, to determine if they can better prevent future strokes in individuals who have recently experienced an ischemic stroke. An ischemic stroke occurs when a blood clot blocks a vessel in the brain, increasing the risk of another stroke soon after. The study compares taking aspirin alone to taking both aspirin and clopidogrel together for 21 days. Individuals who have had an ischemic stroke treated within the last 24 hours and are at low risk of bleeding are suitable candidates for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on anticoagulation medication for reasons other than DVT prevention, you may not be eligible to participate.

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

Studies have shown that taking clopidogrel and aspirin together can reduce the chance of another stroke soon after the first one. Research indicates that this combination lowers the risk of more strokes in the first three months. However, using both medications can also increase the risk of bleeding.

The main concern with these two medications is the risk of bleeding. Before joining studies like this one, patients undergo careful screening to ensure a low risk of bleeding. Doctors typically recommend using the combination for a short period, up to 21 days, to balance the benefits and risks.

These findings suggest that while clopidogrel and aspirin together can be helpful, they should be used cautiously, especially due to the bleeding risk. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining Clopidogrel with Aspirin for stroke treatment because this dual antiplatelet approach might offer enhanced protection against stroke recurrence compared to using Aspirin alone, which is the current standard. Most stroke treatments focus on preventing blood clots by inhibiting platelet aggregation, and while Aspirin does this effectively, adding Clopidogrel could potentially improve outcomes by targeting a different platelet activation pathway. This combination could provide more comprehensive prevention against strokes, offering hope for better recovery and fewer side effects.

What evidence suggests that this trial's treatments could be effective for preventing recurrent strokes?

This trial will compare the effectiveness of two treatment approaches for stroke prevention. Participants in the Dual Antiplatelet Group will receive both clopidogrel and aspirin. Studies have shown that this combination can lower the risk of another stroke after an initial ischemic stroke, reducing the chance of a repeat stroke from 5% to 3.3% compared to using only aspirin. This combination is particularly effective in preventing more strokes within the first three months after a stroke. However, taking these medications together can increase the risk of bleeding. Meanwhile, participants in the Aspirin Group will receive aspirin alone. Overall, using clopidogrel and aspirin together appears to provide better protection against repeat strokes than using aspirin alone. ^{1 4 5 6 7}

Who Is on the Research Team?

Brian H. Buck, MD, FRCPC

Principal Investigator

University of Alberta

Mahesh Kate

Principal Investigator

University of Alberta

Are You a Good Fit for This Trial?

This trial is for patients who've had an ischemic stroke and have been treated with thrombectomy or IV thrombolysis. They must be at low risk of bleeding to participate, as determined by screening after their initial treatment.

Inclusion Criteria

Mild to moderate deficit defined as a National Institute of Health stroke scale of less than or equal to 11 at the time of randomization

Signed informed consent from the patient or legally authorized representative

I was enrolled in the study within 24 hours after my clot removal treatment.

Exclusion Criteria

I have not had bleeding in my stomach, intestines, or urinary tract in the last 3 weeks.

My brain scan score after treatment is below 8.

Participation in another clinical trial

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 days

Treatment

Participants are randomly assigned to take either aspirin alone or aspirin and clopidogrel for 21 days for recurrent stroke prevention

21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

What Are the Treatments Tested in This Trial?

Interventions

• Aspirin
• Clopidogrel

Trial Overview The CoPrime study tests if taking aspirin plus clopidogrel (dual antiplatelet treatment) is safer and more effective than just aspirin in preventing another stroke within the first 21 days post-treatment.

How Is the Trial Designed?

Group I: Dual Antiplatelet Group Experimental Treatment 1 Intervention

Group II: Aspirin Group Active Control 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?

University of Alberta

Lead Sponsor

Trials

957

Recruited

437,000+

Published Research Related to This Trial

In a meta-analysis of five studies involving 29,357 patients with recent ischemic stroke, clopidogrel was found to significantly reduce the risk of major cardiovascular and cerebrovascular events compared to aspirin, with a risk ratio of 0.72.

Clopidogrel also demonstrated a lower risk of bleeding events compared to aspirin (risk ratio 0.57), while there was no difference in all-cause mortality between the two treatments, suggesting clopidogrel may be a safer and more effective option for secondary prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benefits and Risks of Clopidogrel vs. Aspirin Monotherapy after Recent Ischemic Stroke: A Systematic Review and Meta-Analysis. Paciaroni, M., Ince, B., Hu, B., et al.[2022]

In a study of 70 patients who had recently experienced an ischemic stroke, combining clopidogrel with aspirin (C+ASA) resulted in significantly greater inhibition of platelet activity compared to aspirin alone (ASA), indicating enhanced antiplatelet protection.

The C+ASA treatment led to notable reductions in various platelet activation markers and microparticle formation, with no serious adverse events reported, suggesting it is a safe and effective option for improving platelet inhibition in stroke patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of clopidogrel and aspirin in combination versus aspirin alone on platelet activation and major receptor expression in patients after recent ischemic stroke: for the Plavix Use for Treatment of Stroke (PLUTO-Stroke) trial. Serebruany, VL., Malinin, AI., Ziai, W., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3979285/

Combination Aspirin and Clopidogrel for Secondary ... Stroke recurrence was significantly reduced in the dual vs the single antiplatelet group (3.3 % vs 5.0 %, RR 0.67, 95 % CI 0.56–0.91); as were total major ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa1800410

Clopidogrel and Aspirin in Acute Ischemic Stroke and High ... Combination antiplatelet therapy with clopidogrel and aspirin may reduce the rate of recurrent stroke during the first 3 months after a minor ischemic stroke ...

3. ahajournals.org ahajournals.org/doi/10.1161/JAHA.123.033611

Trends in Dual Antiplatelet Therapy of Aspirin and ... From 2011 to 2022, clinical outcomes nonsignificantly improved, with an average relative risk reduction of 2%/y for the composite of stroke, ...

4. strokebestpractices.ca strokebestpractices.ca/recommendations/secondary-prevention-of-stroke/anti-platelet-therapy-in-ischemic-stroke-and-tia

6. Antiplatelet Therapy for Ischemic Stroke and Transient ... The short-term use of the combination of clopidogrel + aspirin vs. aspirin alone, has been shown to reduce the risk of additional ischemic vascular events ...

5. sciencedirect.com sciencedirect.com/topics/medicine-and-dentistry/acetylsalicylic-acid-plus-clopidogrel

Acetylsalicylic Acid Plus Clopidogrel - an overview Acetylsalicylic acid is the traditional first line agent in prevention of ischaemic stroke with a 22% reduction in the odds of a recurrent stroke.3 Clopidogrel ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8225168/

A Combination of Aspirin and Clopidogrel Predict More ... The updated guidelines regarding acute stroke management recommend the combined use of clopidogrel and aspirin for a period of 21 days, then the ...

7. ahajournals.org ahajournals.org/doi/10.1161/hs1201.100829

Combination Therapy With Clopidogrel and Aspirin | Stroke In this trial, the benefit of clopidogrel over aspirin for the prevention of vascular events was a relative risk reduction of 8.7%. In addition, there was less ...