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Chronic Kidney Disease (CKD)Phase 4NCT03774394

Impact of Chronic Kidney Disease on Clopidogrel Effects in Diabetes Mellitus

A Phase 4 study testing Clopidogrel and Clopidogrel active metabolite in people with Chronic Kidney Disease (CKD) and Type 2 Diabetes Mellitus (T2DM), run by University of Florida at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Clopidogrel and Clopidogrel active metabolite
Could I receive a placebo?
No, everyone receives an active treatment
How many people
61 participants
Where
1 siteUnited States
Study dates
22 Aug 2019to 31 May 2022
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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
Show all 13Show fewer
  • 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).

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Florida Jacksonville

    Jacksonville, Florida, 32209

Other trials in United States

About this study

Official title: Impact of Chronic Kidney Disease (CKD) on Pharmacodynamic Profiles of the P2Y12 Receptor Inhibitor Clopidogrel in the Setting of Type 2 Diabetes Mellitus (T2DM) and Coronary Artery Disease (CAD)

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.

Read the detailed description

Patients with diabetes mellitus (DM) and coexisting chronic kidney disease (CKD) are at increased risk of atherothrombotic events, underscoring the importance of secondary prevention antiplatelet therapy in these high-risk patients. Clopidogrel is the most widely used platelet P2Y12 receptor inhibitor in patients with coronary artery disease (CAD). However, despite its clinical benefits, many patients still experience recurrent atherothrombotic events. This is in part due to the impaired effects of clopidogrel in DM patients, particularly among those with coexisting CKD. However, underlying mechanism(s) leading to magnification of impaired clopidogrel response among DM patients with CKD remain unexplored. The ever growing prevalence of CKD in patients with DM and their high risk of recurrent events underscores the need to define such mechanism(s) as this may set the basis for identifying treatment regimens leading to more effective platelet inhibition and cardiovascular protection in these high-risk patients. 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. Comprehensive pharmacokinetic and pharmacodynamic assessments, including ex vivo and in vitro experiments, evaluating the impact of CKD on antiplatelet drug response in DM patients are proposed.

Being tested
Clopidogrel, Clopidogrel active metabolite
Keywords
pharmacodynamics (PD), pharmacokinetic (PK), clopidogrel
Medical subject headings
Renal Insufficiency, Chronic, Diabetes Mellitus, Type 2, Coronary Artery Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ClopidogrelDrug

    Also called Plavix

    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.

  • Clopidogrel active metaboliteDrug

    Also called Plavix

    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)

Study groups in NCT03774394
Study groupRoleWhat they receive
Diabetes Mellitus patients with Chronic Kidney DiseaseExperimentalPatients 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.
Receives: Drug: Clopidogrel; Drug: Clopidogrel active metabolite
Diabetes Mellitus patients without Chronic Kidney DiseaseActive 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.
Receives: Drug: Clopidogrel; Drug: Clopidogrel active metabolite

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 6 hours

Secondary outcomes (1)

  1. Clopidogrel Active Metabolite Concentration

    Comparison of clopidogrel active metabolite plasma concentrations by means of AUC

    Measured: 6 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Dec 2018
  2. Study start22 Aug 2019
  3. Primary completion23 May 2022
  4. Study completion31 May 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
61 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03774394
Sponsor's protocol ID
IRB201801870 -A
Status last verified
Jul 2023
First submitted
11 Dec 2018
Last updated
21 Aug 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 39170956

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Clopidogrel and Clopidogrel active metabolite in people with Chronic Kidney Disease (CKD) and Type 2 Diabetes Mellitus (T2DM), run by University of Florida at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Platelet Reactivity Index (PRI) Assessed by VASP. The Cutoff for High Platelet Reactivity is >50% (time frame: 6 hours). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03774394, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Aug 2023.

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