Trial Outcomes & Findings for Impact of Chronic Kidney Disease on Clopidogrel Effects in Diabetes Mellitus (NCT NCT03774394)

NCT ID: NCT03774394

Last Updated: 2023-08-21

Results Overview

Comparison of platelet reactivity measured as PRI assessed by VASP after a 600 mg clopidogrel LD between DM patients with and without CKD

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 61 participants
• Primary outcome timeframe: 6 hours
• Results posted on: 2023-08-21

Participant Flow

Participant milestones

Measure	Diabetes Mellitus Patients With Chronic Kidney Disease Patients 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. Clopidogrel: 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 metabolite: 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)	Diabetes Mellitus Patients Without Chronic Kidney Disease Patients 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. Clopidogrel: 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 metabolite: 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)
Overall Study STARTED	31	30
Overall Study COMPLETED	29	30
Overall Study NOT COMPLETED	2	0

Reasons for withdrawal

Measure	Diabetes Mellitus Patients With Chronic Kidney Disease Patients 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. Clopidogrel: 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 metabolite: 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)	Diabetes Mellitus Patients Without Chronic Kidney Disease Patients 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. Clopidogrel: 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 metabolite: 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)
Overall Study Withdrawal by Subject	2	0

Baseline Characteristics

Impact of Chronic Kidney Disease on Clopidogrel Effects in Diabetes Mellitus

Baseline characteristics by cohort

Measure	Diabetes Mellitus Patients With Chronic Kidney Disease n=31 Participants Patients 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. Clopidogrel: 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 metabolite: 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)	Diabetes Mellitus Patients Without Chronic Kidney Disease n=30 Participants Patients 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. Clopidogrel: 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 metabolite: 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)	Total n=61 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	9 Participants n=5 Participants	17 Participants n=7 Participants	26 Participants n=5 Participants
Age, Categorical >=65 years	22 Participants n=5 Participants	13 Participants n=7 Participants	35 Participants n=5 Participants
Age, Continuous	68.4 years STANDARD_DEVIATION 10.8 • n=5 Participants	65.2 years STANDARD_DEVIATION 6.8 • n=7 Participants	66.7 years STANDARD_DEVIATION 8.9 • n=5 Participants
Sex: Female, Male Female	17 Participants n=5 Participants	17 Participants n=7 Participants	34 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	13 Participants n=7 Participants	27 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	9 Participants n=5 Participants	15 Participants n=7 Participants	24 Participants n=5 Participants
Race (NIH/OMB) White	21 Participants n=5 Participants	15 Participants n=7 Participants	36 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	31 participants n=5 Participants	30 participants n=7 Participants	61 participants n=5 Participants
Prior myocardial infarction	12 Participants n=5 Participants	9 Participants n=7 Participants	21 Participants n=5 Participants

PRIMARY outcome

Timeframe: 6 hours

Comparison of platelet reactivity measured as PRI assessed by VASP after a 600 mg clopidogrel LD between DM patients with and without CKD

Outcome measures

Measure	Diabetes Mellitus Patients With Chronic Kidney Disease n=29 Participants Patients 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. Clopidogrel: 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 metabolite: 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)	Diabetes Mellitus Patients Without Chronic Kidney Disease n=30 Participants Patients 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. Clopidogrel: 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 metabolite: 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)
Platelet Reactivity Index (PRI) Assessed by VASP. The Cutoff for High Platelet Reactivity is >50%	67.5 PRI% Standard Deviation 27.4	67.2 PRI% Standard Deviation 30.2

SECONDARY outcome

Timeframe: 6 hours

Comparison of clopidogrel active metabolite plasma concentrations by means of AUC

Outcome measures

Measure	Diabetes Mellitus Patients With Chronic Kidney Disease n=29 Participants Patients 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. Clopidogrel: 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 metabolite: 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)	Diabetes Mellitus Patients Without Chronic Kidney Disease n=30 Participants Patients 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. Clopidogrel: 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 metabolite: 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)
Clopidogrel Active Metabolite Concentration	47.1 ng*h/mL Interval 32.8 to 62.7	39.6 ng*h/mL Interval 19.8 to 85.8

OTHER_PRE_SPECIFIED outcome

Timeframe: 6 hours

Comparison of platelet reactivity measured as PRU assessed by VerifyNow after a 600 mg clopidogrel LD between DM patients with and without CKD

Outcome measures

Measure	Diabetes Mellitus Patients With Chronic Kidney Disease n=29 Participants Patients 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. Clopidogrel: 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 metabolite: 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)	Diabetes Mellitus Patients Without Chronic Kidney Disease n=30 Participants Patients 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. Clopidogrel: 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 metabolite: 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)
P2Y12 Reaction Units (PRU) Assessed by VerifyNow. The Cutoff for High Platelet Reactivity is >208.	164 PRU Standard Deviation 91	156 PRU Standard Deviation 92

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline

Comparison of of platelet reactivity measured as PRI assessed by VASP after incubation with clopidogrel active metabolite between DM patients with and without CKD

Outcome measures

Measure	Diabetes Mellitus Patients With Chronic Kidney Disease n=29 Participants Patients 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. Clopidogrel: 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 metabolite: 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)	Diabetes Mellitus Patients Without Chronic Kidney Disease n=30 Participants Patients 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. Clopidogrel: 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 metabolite: 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)
Platelet Reactivity Index (PRI) Assessed by VASP. The Cutoff for High Platelet Reactivity is >50%	92.7 PRI% Standard Deviation 5.6	94.4 PRI% Standard Deviation 3.5

Adverse Events

Diabetes Mellitus Patients With Chronic Kidney Disease

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Diabetes Mellitus Patients Without Chronic Kidney Disease

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Francesco Franchi, MD

University of Florida

Phone: +1-904-244-2060

Email: francesco.franchi@jax.ufl.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place