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

Trial Summary

What is the purpose of this trial?

Stroke is a common cause of disability. The most common type of stroke, an ischemic stroke, is caused by a blood vessel in the brain getting blocked by a clot. When this happens, part of the brain is damaged because it is not getting the blood supply it needs. To treat this type of stroke, doctors give medication and/or do a procedure to remove the blockage and restore blood supply to the brain. Unfortunately, patients who have had an ischemic stroke are at higher risk of having another ischemic stroke. This risk is highest in the first 21 days after a stroke. Currently, doctors give patients the medication aspirin every day, starting 24 hours after stroke treatment, to prevent recurrent strokes. However, some studies have shown that giving another medication, clopidogrel, in addition to aspirin, is safe and may work better than aspirin alone at preventing repeat strokes. Both aspirin and clopidogrel are a type of medication called an antiplatelet that prevents clots from forming in the blood. When both medications are given together, it is called dual antiplatelet treatment. The main risk of antiplatelet medications is bleeding. This research aims to study the safety and feasibility of using dual antiplatelet treatment to prevent recurrent strokes. Patients who have received treatment for an ischemic stroke will first be screened to rule out patients at high risk of bleeding. Following informed consent, patients at low risk of bleeding will be enrolled in the study 24 hours after their initial stroke treatment. Patients will be randomly assigned to either take aspirin alone or aspirin and clopidogrel for 21 days for recurrent stroke prevention. The study team will then follow patients for three months after treatment to collect information about their recovery and assess differences between the two groups.

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.

What data supports the effectiveness of the drug combination of Clopidogrel and Aspirin for stroke prevention?

Research shows that combining Clopidogrel with Aspirin can provide more potent platelet inhibition (preventing blood cells from clumping together) than Aspirin alone in patients who have had an ischemic stroke. Additionally, patients with a higher risk of recurrent stroke were more likely to benefit from the Clopidogrel-Aspirin combination, reducing the risk of future vascular events. ^{1 2 3 4 5}

Is the combination of clopidogrel and aspirin safe for stroke patients?

The combination of clopidogrel and aspirin may increase the risk of serious bleeding in stroke patients, so it should be used with caution and for the shortest time possible, especially after coronary procedures. ^{1 2 4 6 7}

How does the drug combination of clopidogrel and aspirin differ from other treatments for stroke?

The combination of clopidogrel and aspirin is unique because it targets different pathways to prevent blood clots, potentially offering more protection against stroke than aspirin alone, although it may increase the risk of bleeding. ^{1 2 4 5 6}

Research Team

Brian H. Buck, MD, FRCPC

Principal Investigator

University of Alberta

Mahesh Kate

Principal Investigator

University of Alberta

Eligibility Criteria

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

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

Signed informed consent from the patient or legally authorized representative

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

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

1. United States 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. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Benefits and Risks of Clopidogrel vs. Aspirin Monotherapy after Recent Ischemic Stroke: A Systematic Review and Meta-Analysis. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Antiplatelet profiles of the fixed-dose combination of extended-release dipyridamole and low-dose aspirin compared with clopidogrel with or without aspirin in patients with type 2 diabetes and a history of transient ischemic attack: a randomized, single-blind, 30-day trial. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Risk of recurrent stroke and antiplatelet choice in breakthrough stroke while on aspirin. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Future perspectives for optimizing oral antiplatelet therapy. [2017]

6. United States pubmed.ncbi.nlm.nih.gov

Results of the management of atherothrombosis with clopidogrel in high-risk patients trial: implications for the neurologist. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Ticagrelor plus aspirin versus clopidogrel plus aspirin for platelet reactivity in patients with minor stroke or transient ischaemic attack: open label, blinded endpoint, randomised controlled phase II trial. [2020]