Efficacy of Clopidogrel on Incidence of Silent Brain Infarction

NCT04698031 | Active Not Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: NURC-021-20S
• Study Type: interventional
• Target: 134
• Locations: 1 country
• Sites: 1

Brief Summary

Silent brain infarctions (SBIs) are a manifestation of covert cerebrovascular disease, without obvious clinical deficit, noted very often in patients presenting with a new stroke or new transient ischemic attack. SBIs are linked to a significant increase in risk for subsequent stroke and cognitive decline. However, no biomarker is currently available that can predict the recurrence of these subclinical lesions. Coated-platelets are a measure of platelet procoagulant potential significantly increased in patients with ischemic stroke or transient ischemic attack compared to unaffected controls. Higher coated-platelet levels are strongly associated with both the presence and number of SBIs. Among medications approved for preventing stroke recurrence, we identified clopidogrel as a pharmacological agent leading to a decrease in coated-platelet levels. In this project, we plan to evaluate if clopidogrel can decrease the rate of occurrence of new silent brain infarctions. The result will enhance the investigators understanding of the relationship between platelets and silent brain infarcts, leading to improved health care delivery and also potential targets for novel preventive pharmacological interventions.

Conditions

Silent Brain Infarction

Outcome Measures

Primary Outcomes (1)

• new silent brain infarctions

  Each of the two reviewers will independently adjudicate the presence, location and number of SBIs for each patient by reviewing both the initial and repeat scans at 24 months.

  24 months

Secondary Outcomes (1)

• cognitive impairment

  24 months

Study Arms (2)

Clopidogrel

EXPERIMENTAL

After randomization, patients will receive clopidogrel mg daily for the duration of the study. The VA Research Pharmacy will dispense similar looking pills (using a "dummy pill") with Arm 2 to ensure the double-blind nature of the intervention. Clopidogrel is FDA approved for secondary prevention of stroke. Patients will be followed for 24 months with repeat brain MRI scans obtained at 24 months.

Drug: Clopidogrel treatment

Aspirin

EXPERIMENTAL

After randomization, patients will receive aspirin daily for the duration of the study. The VA Research Pharmacy will dispense similar looking pills (using a "dummy pill") with Arm 1 to ensure the double-blind nature of the intervention. Aspirin is FDA approved for secondary prevention of stroke. Patients will be followed for 24 months with repeat brain MRI scans obtained at 24 months.

Drug: Aspirin treatment

Interventions

Clopidogrel treatment DRUG

After randomization, patients will receive clopidogrel 75 mg daily for the duration of the study. The VA Research Pharmacy will dispense similar looking medication with Arm 2 to ensure the double-blind nature of the intervention. Clopidogrel is FDA approved for secondary prevention of stroke. Follow-up will be for 24 months with repeat brain MRI obtained at 24 months to assess for interval presence of silent brain infarctions.

Clopidogrel

Aspirin treatment DRUG

After randomization, patients will receive Aspirin 325 mg daily for the duration of the study. The VA Research Pharmacy will dispense similar looking medication with Arm 2 to ensure the double-blind nature of the intervention. Aspirin is FDA approved for secondary prevention of stroke. Follow-up will be for 24 months with repeat brain MRI obtained at 24 months to assess for interval presence of silent brain infarctions.

Aspirin

Eligibility Criteria

• Age: 21 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• diagnosis of ischemic stroke/TIA
• \< 90 days from onset of symptoms
• initial MRI available,
• not receiving antiplatelet therapy at the time of admission
• medical decision by the treating physician that antiplatelet therapy is indicated for secondary prevention (decision independent of the study and based on individual clinical decision for each patient).
• baseline coated-platelet levels at 40%,
• willingness to participate in the study for 24 months

You may not qualify if:

• dementia (based on chart review or self/proxy report)
• \> 90 days from onset of symptoms
• initiation of anticoagulation or thrombolytics prior to phlebotomy
• intracranial hemorrhage or bleeding diatheses
• end-stage renal disease (ESRD)
• inability to tolerate consenting or phlebotomy
• prior adverse/allergic reactions to clopidogrel
• treating physician deemed a different antiplatelet dose or dual antiplatelet therapy as the only treatment choice

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

Oklahoma City VA Medical Center, Oklahoma City, OK

Oklahoma City, Oklahoma, 73104-5007, United States

Location

Related Publications (1)

• Kwan J, Hafdi M, Chiang LLW, Myint PK, Wong LS, Quinn TJ. Antithrombotic therapy to prevent cognitive decline in people with small vessel disease on neuroimaging but without dementia. Cochrane Database Syst Rev. 2022 Jul 14;7(7):CD012269. doi: 10.1002/14651858.CD012269.pub2.

  PMID: 35833913 DERIVED

Study Officials

• Calin Ioan Prodan, MD

  Oklahoma City VA Medical Center, Oklahoma City, OK

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The two stroke neurologists reviewing the brain MRI scans will independently adjudicate the presence and number of SBIs for each patient by reviewing the initial and repeat scans, along with the medical history. Each adjudicator will maintain a log with the results and a study identification number while blinded to the platelet procoagulant levels and intervention arm distribution. The laboratory staff will be blinded to clinical, imaging and intervention data. The VA Research Pharmacy will dispense similar looking pills to ensure the double-blind nature of the intervention.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: Patients admitted for stroke/TIA, with indication for antiplatelet therapy as secondary prevention (decision independent of the study and based on individual clinical decision for each patient by the treating physician), will be assigned to therapy with either clopidogrel or aspirin. Both medications are FDA approved for secondary prevention. Patients will be followed for 24 months and repeat brain MRI will be obtained at 24 months. These doses are part of the recommended guidelines for secondary stroke prevention. After randomization, an electronic prescription will be signed by the PI (flagged as part of the research protocol) for a 90-day supply with multiple refills. The medication will be delivered prior to discharge.

Study Record Dates

• First Submitted: December 28, 2020
• First Posted: January 6, 2021
• Study Start: March 30, 2022
• Primary Completion: May 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: January 29, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)