Impact of Chronic Kidney Disease on Clopidogrel Effects in Diabetes Mellitus

• ClinicalTrials.gov Identifier: NCT03774394
• Recruitment Status: Completed
• First Posted: December 13, 2018
• Results First Posted: August 21, 2023
• Last Update Posted: August 21, 2023
• Sponsor: University of Florida
• Collaborator: Scott R. MacKenzie Foundation
• Information provided by (Responsible Party): University of Florida

• Study Type: Interventional
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Chronic Kidney Disease (CKD); Type 2 Diabetes Mellitus (T2DM); Coronary Artery Disease (CAD)
• Interventions: Drug: Clopidogrel; Drug: Clopidogrel active metabolite
• Enrollment: 61

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Diabetes Mellitus Patients With Chronic Kidney Disease	Diabetes Mellitus Patients Without Chronic Kidney Disease
Arm/Group Description	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)	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)
Period Title: Overall Study
Started	31	30
Completed	29	30
Not Completed	2	0
Reason Not Completed
Withdrawal by Subject	2	0

Baseline Characteristics

Arm/Group Title		Diabetes Mellitus Patients With Chronic Kidney Disease	Diabetes Mellitus Patients Without Chronic Kidney Disease	Total
Arm/Group Description		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)	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 of all reporting groups
Overall Number of Baseline Participants		31	30	61
Baseline Analysis Population Description		Patient with diabetes and stable coronary artery disease not on a P2Y12 inhibitor.
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	31 participants	30 participants	61 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	9 29.0%	17 56.7%	26 42.6%
	>=65 years	22 71.0%	13 43.3%	35 57.4%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	31 participants	30 participants	61 participants
		68.4 (10.8)	65.2 (6.8)	66.7 (8.9)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	31 participants	30 participants	61 participants
	Female	17 54.8%	17 56.7%	34 55.7%
	Male	14 45.2%	13 43.3%	27 44.3%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	31 participants	30 participants	61 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	0 0.0%	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	9 29.0%	15 50.0%	24 39.3%
	White	21 67.7%	15 50.0%	36 59.0%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	1 3.2%	0 0.0%	1 1.6%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	31 participants	30 participants	61 participants
		31	30	61
Prior myocardial infarction; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	31 participants	30 participants	61 participants
		12 38.7%	9 30.0%	21 34.4%

Outcome Measures

1. Primary Outcome

Title	Platelet Reactivity Index (PRI) Assessed by VASP. The Cutoff for High Platelet Reactivity is >50%
Description	Comparison of platelet reactivity measured as PRI assessed by VASP after a 600 mg clopidogrel LD between DM patients with and without CKD
Time Frame	6 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Diabetes Mellitus Patients With Chronic Kidney Disease	Diabetes Mellitus Patients Without Chronic Kidney Disease
Arm/Group Description:	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)	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 Number of Participants Analyzed	29	30
Mean (Standard Deviation); Unit of Measure: PRI%
	67.5 (27.4)	67.2 (30.2)

2. Secondary Outcome

Title	Clopidogrel Active Metabolite Concentration
Description	Comparison of clopidogrel active metabolite plasma concentrations by means of AUC
Time Frame	6 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Diabetes Mellitus Patients With Chronic Kidney Disease	Diabetes Mellitus Patients Without Chronic Kidney Disease
Arm/Group Description:	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)	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 Number of Participants Analyzed	29	30
Median (Inter-Quartile Range); Unit of Measure: ng*h/mL
	47.1; (32.8 to 62.7)	39.6; (19.8 to 85.8)

3. Other Pre-specified Outcome

Title	P2Y12 Reaction Units (PRU) Assessed by VerifyNow. The Cutoff for High Platelet Reactivity is >208.
Description	Comparison of platelet reactivity measured as PRU assessed by VerifyNow after a 600 mg clopidogrel LD between DM patients with and without CKD
Time Frame	6 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Diabetes Mellitus Patients With Chronic Kidney Disease	Diabetes Mellitus Patients Without Chronic Kidney Disease
Arm/Group Description:	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)	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 Number of Participants Analyzed	29	30
Mean (Standard Deviation); Unit of Measure: PRU
	164 (91)	156 (92)

4. Other Pre-specified Outcome

Title	Platelet Reactivity Index (PRI) Assessed by VASP. The Cutoff for High Platelet Reactivity is >50%
Description	Comparison of of platelet reactivity measured as PRI assessed by VASP after incubation with clopidogrel active metabolite between DM patients with and without CKD
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Diabetes Mellitus Patients With Chronic Kidney Disease	Diabetes Mellitus Patients Without Chronic Kidney Disease
Arm/Group Description:	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)	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 Number of Participants Analyzed	29	30
Mean (Standard Deviation); Unit of Measure: PRI%
	92.7 (5.6)	94.4 (3.5)

Adverse Events

Time Frame	24 hours
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Diabetes Mellitus Patients With Chronic Kidney Disease	Diabetes Mellitus Patients Without Chronic Kidney Disease
Arm/Group Description	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)	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)
All-Cause Mortality
	Diabetes Mellitus Patients With Chronic Kidney Disease	Diabetes Mellitus Patients Without Chronic Kidney Disease
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/31 (0.00%)	0/30 (0.00%)
Serious Adverse Events
	Diabetes Mellitus Patients With Chronic Kidney Disease	Diabetes Mellitus Patients Without Chronic Kidney Disease
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/31 (0.00%)	0/30 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Diabetes Mellitus Patients With Chronic Kidney Disease	Diabetes Mellitus Patients Without Chronic Kidney Disease
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/31 (0.00%)	0/30 (0.00%)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Francesco Franchi, MD
• Organization: University of Florida
• Phone: +1-904-244-2060
• EMail: francesco.franchi@jax.ufl.edu

• Responsible Party: University of Florida
• ClinicalTrials.gov Identifier: NCT03774394
• Other Study ID Numbers: IRB201801870 -A
• First Submitted: December 11, 2018
• First Posted: December 13, 2018
• Results First Submitted: June 29, 2023
• Results First Posted: August 21, 2023
• Last Update Posted: August 21, 2023