Impact of Chronic Kidney Disease on Clopidogrel Effects in Diabetes Mellitus
1 other identifier
interventional
61
1 country
1
Brief Summary
Patients with diabetes mellitus (DM) and chronic kidney disease (CKD) are at increased risk of atherothrombotic events. Clopidogrel is the most widely used platelet P2Y12 receptor inhibitor in patients with coronary artery disease (CAD). However, despite its benefits, many patients still experience recurrent atherothrombotic events. The proposed study will test the central hypothesis that in DM patients the presence of CKD reduces clopidogrel-mediated P2Y12 inhibitory effects through synergistic mechanisms, which include upregulation of the P2Y12 signaling pathway and impaired clopidogrel metabolism.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_4
Started Aug 2019
Typical duration for phase_4
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 11, 2018
CompletedFirst Posted
Study publicly available on registry
December 13, 2018
CompletedStudy Start
First participant enrolled
August 22, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 23, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
May 31, 2022
CompletedResults Posted
Study results publicly available
August 21, 2023
CompletedAugust 21, 2023
July 1, 2023
2.8 years
December 11, 2018
June 29, 2023
July 24, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Platelet Reactivity Index (PRI) Assessed by VASP. The Cutoff for High Platelet Reactivity is >50%
Comparison of platelet reactivity measured as PRI assessed by VASP after a 600 mg clopidogrel LD between DM patients with and without CKD
6 hours
Secondary Outcomes (1)
Clopidogrel Active Metabolite Concentration
6 hours
Other Outcomes (2)
P2Y12 Reaction Units (PRU) Assessed by VerifyNow. The Cutoff for High Platelet Reactivity is >208.
6 hours
Platelet Reactivity Index (PRI) Assessed by VASP. The Cutoff for High Platelet Reactivity is >50%
Baseline
Study Arms (2)
Diabetes Mellitus patients with Chronic Kidney Disease
EXPERIMENTALPatients with CKD will be administered a 600-mg LD of Clopidogrel followed by a single 75-mg MD administered after 24 hours. Blood samples collected at baseline will be incubated with clopidogrel active metabolite.
Diabetes Mellitus patients without Chronic Kidney Disease
ACTIVE COMPARATORPatients without CKD will be administered a 600-mg LD of Clopidogrel followed by a single 75-mg MD administered after 24 hours. Blood samples collected at baseline will be incubated with clopidogrel active metabolite.
Interventions
Both CKD and Non-CKD patients will be administered a 600-mg LD of clopidogrel followed by a single 75-mg MD administered after 24 hours.
In both CKD and Non-CKD patients, blood samples collected at baseline only (before clopidogrel LD administration) will be incubated with escalating concentrations of clopidogrel active metabolite (1, 3 and 10 μM)
Eligibility Criteria
You may qualify if:
- Type 2 DM, defined according to ADA definition, on treatment with oral hypoglycemic agents and/or insulin
- Angiographically documented CAD
- On treatment with low-dose aspirin (81mg/day) for ≥30 days as part of standard of care.
You may not qualify if:
- Use of any antiplatelet therapy (except aspirin) in prior 30 days
- Use of parenteral or oral anticoagulation
- Active bleeding
- High risk of bleeding
- Clinical indication to be on a P2Y12 receptor inhibitor
- End-stage renal disease on hemodialysis
- Any active malignancy
- Platelet count \< 100x106/µl
- Hemoglobin \<9 g/dl
- Severe known liver disease
- Hemodynamic instability
- Known allergy to clopidogrel
- Pregnant / lactating females (women of childbearing age must use reliable birth control).
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Floridalead
- Scott R. MacKenzie Foundationcollaborator
Study Sites (1)
University of Florida Jacksonville
Jacksonville, Florida, 32209, United States
Related Publications (1)
Ortega-Paz L, Franchi F, Rollini F, Galli M, Been L, Ghanem G, Shalhoub A, Ossi T, Rivas A, Zhou X, Pineda AM, Suryadevara S, Soffer D, Zenni MM, Mahowald MK, Langaee T, Jakubowski JA, Cavallari LH, Angiolillo DJ. Clopidogrel-Mediated P2Y12 Inhibition According to Renal Function in Patients With Diabetes Mellitus and CAD. JACC Basic Transl Sci. 2024 Mar 25;9(7):865-876. doi: 10.1016/j.jacbts.2024.03.003. eCollection 2024 Jul.
PMID: 39170956DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Francesco Franchi, MD
- Organization
- University of Florida
Study Officials
- PRINCIPAL INVESTIGATOR
Francesco Franchi, MD
University of Florida
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 11, 2018
First Posted
December 13, 2018
Study Start
August 22, 2019
Primary Completion
May 23, 2022
Study Completion
May 31, 2022
Last Updated
August 21, 2023
Results First Posted
August 21, 2023
Record last verified: 2023-07
Data Sharing
- IPD Sharing
- Will not share