Trial Outcomes & Findings for Investigation of the Athero-Protective Effects of Clopidogrel (NCT NCT01283282)

Results Overview

Flow-mediated dilation (FMD) collected by an ultrasound and is measured by the percent change in diameter of the brachial artery from baseline to 12 weeks.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

48 participants

Primary outcome timeframe

Baseline, Week 12

Results posted on

2015-05-01

Participant Flow

Patients recruited from clinic sites at Emory University Hospital, Crawford Long Hospital, Grady Memorial Hospital and VA Medical Center between January 2008 through December 2008.

Participant milestones

Participant milestones
Measure	Placebo First/Then Clopidogrel The subjects received placebo PO qd for the first 6 weeks then were switched to clopidogrel 75 mg PO qd therapy for an additional 6 weeks without any wash out period in between.	Clopidogrel First/Then Placebo The subjects received clopidogrel 75 mg PO qd for the first 6 weeks then were switched to placebo PO qd therapy for an additional 6 weeks without any wash out period in between.
First Intervention (6 Weeks) STARTED	25	23
First Intervention (6 Weeks) COMPLETED	22	19
First Intervention (6 Weeks) NOT COMPLETED	3	4
Second Intervention (6 Weeks) STARTED	22	19
Second Intervention (6 Weeks) COMPLETED	22	19
Second Intervention (6 Weeks) NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo First/Then Clopidogrel The subjects received placebo PO qd for the first 6 weeks then were switched to clopidogrel 75 mg PO qd therapy for an additional 6 weeks without any wash out period in between.	Clopidogrel First/Then Placebo The subjects received clopidogrel 75 mg PO qd for the first 6 weeks then were switched to placebo PO qd therapy for an additional 6 weeks without any wash out period in between.
First Intervention (6 Weeks) Physician Decision	0	1
First Intervention (6 Weeks) Withdrawal by Subject	2	3
First Intervention (6 Weeks) Lost to Follow-up	1	0

Baseline Characteristics

Investigation of the Athero-Protective Effects of Clopidogrel

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Subjects n=41 Participants The subjects received clopidogrel 75 mg or placebo PO qd for the first 6 weeks then were switched to receive either placebo or clopidogrel 75 mg PO qd therapy for an additional 6 weeks without any wash out period in between.
Age, Continuous	63 years STANDARD_DEVIATION 1.5 • n=5 Participants
Sex: Female, Male Female	15 Participants n=5 Participants
Sex: Female, Male Male	26 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 12

Flow-mediated dilation (FMD) collected by an ultrasound and is measured by the percent change in diameter of the brachial artery from baseline to 12 weeks.

Outcome measures

Outcome measures
Measure	Clopridogrel n=41 Participants The subjects received clopidogrel 75 mg PO qd for the first 6 weeks or received clopidogrel 75 mg PO qd for the last 6 weeks.	Placebo n=41 Participants The subjects received placebo PO qd for the first 6 weeks or the subjects received placebo PO qd for the last 6 weeks.
Flow-mediated Dilation (FMD)	4.89 percent change in diameter Standard Error 0.59	4.81 percent change in diameter Standard Error 0.59

PRIMARY outcome

Timeframe: Baseline, Week 12

Nitroglycerin (NTG)-mediated vasodilation was measured after 0.4 mg of NTG was administered sublingually. Brachial artery images were obtained via ultrasound after three minutes of NTG administration. Measurements from the twelve frames will be averaged to calculate the percent change in diameter of the brachial artery from baseline to 12 weeks.

Outcome measures

Outcome measures
Measure	Clopridogrel n=41 Participants The subjects received clopidogrel 75 mg PO qd for the first 6 weeks or received clopidogrel 75 mg PO qd for the last 6 weeks.	Placebo n=41 Participants The subjects received placebo PO qd for the first 6 weeks or the subjects received placebo PO qd for the last 6 weeks.
Nitroglycerin-mediated Vasodilation	19.31 percent change in diameter Standard Error 1.49	17.10 percent change in diameter Standard Error 1.51

PRIMARY outcome

Timeframe: Week 12

The circulating progenitor-enriched population of cells was measured by the expression of surface antigens using direct flow cytometry for CD34+, CD34+/CD133+, CD34+/ VEGF2R+ and CD34+/CD133+/VEGF2R+

Outcome measures

Outcome measures
Measure	Clopridogrel n=41 Participants The subjects received clopidogrel 75 mg PO qd for the first 6 weeks or received clopidogrel 75 mg PO qd for the last 6 weeks.	Placebo n=41 Participants The subjects received placebo PO qd for the first 6 weeks or the subjects received placebo PO qd for the last 6 weeks.
Endothelial Progenitor Cells (EPCs) CD34+	1.46 cells/µL Standard Error 0.16	1.54 cells/µL Standard Error 0.21
Endothelial Progenitor Cells (EPCs) CD34+/133+	0.68 cells/µL Standard Error 0.07	0.75 cells/µL Standard Error 0.16
Endothelial Progenitor Cells (EPCs) CD34+/VEGF2R+	0.08 cells/µL Standard Error 0.03	0.09 cells/µL Standard Error 0.02
Endothelial Progenitor Cells (EPCs) CD34+/CD133+/VEGF2R+	0.03 cells/µL Standard Error 0.009	0.03 cells/µL Standard Error 0.008

SECONDARY outcome

Timeframe: Week 12

PWV was measured between the carotid and femoral arteries using the SphygmoCor device. Pressure waveforms at the carotid and femoral arteries were acquired using EKG gating. Velocity (distance per time in seconds) was calculated using the foot-to-foot method and the distance between the sites was measured manually.

Outcome measures

Outcome measures
Measure	Clopridogrel n=41 Participants The subjects received clopidogrel 75 mg PO qd for the first 6 weeks or received clopidogrel 75 mg PO qd for the last 6 weeks.	Placebo n=41 Participants The subjects received placebo PO qd for the first 6 weeks or the subjects received placebo PO qd for the last 6 weeks.
Pulse Wave Velocity (PWV)	8.77 m/s Standard Error 0.45	9.044 m/s Standard Error 0.45

SECONDARY outcome

Timeframe: Week 12

Oxidative stress was measured by using liquid chromatography to collect plasma cystine, cysteine, gluthione, and oxidized glutathione levels.

Outcome measures

Outcome measures
Measure	Clopridogrel n=41 Participants The subjects received clopidogrel 75 mg PO qd for the first 6 weeks or received clopidogrel 75 mg PO qd for the last 6 weeks.	Placebo n=41 Participants The subjects received placebo PO qd for the first 6 weeks or the subjects received placebo PO qd for the last 6 weeks.
Oxidative Stress Markers Cystine	105.25 µM Standard Error 7.36	102.39 µM Standard Error 7.29
Oxidative Stress Markers Cysteine	13.71 µM Standard Error 0.90	14.75 µM Standard Error 0.89
Oxidative Stress Markers Glutathione	1.52 µM Standard Error 0.17	1.71 µM Standard Error 0.17
Oxidative Stress Markers Oxidized glutathione	0.08 µM Standard Error 0.06	0.19 µM Standard Error 0.06

SECONDARY outcome

Timeframe: Week 12

High-sensitivity C-reactive protein (hsCRP) was measured. The hsCRP levels were measured by Dade Behring nephelometry.

Outcome measures

Outcome measures
Measure	Clopridogrel n=41 Participants The subjects received clopidogrel 75 mg PO qd for the first 6 weeks or received clopidogrel 75 mg PO qd for the last 6 weeks.	Placebo n=41 Participants The subjects received placebo PO qd for the first 6 weeks or the subjects received placebo PO qd for the last 6 weeks.
Inflammatory Marker High-sensitivity C-reactive Protein (hsCRP)	5.98 mg/L Standard Error 1.95	4.31 mg/L Standard Error 1.95

SECONDARY outcome

Timeframe: Week 12

CD40 ligand levels were measured. The level of CD40 ligand were measured using the Flurokine MultiAnalyte profiling (MAP) Human Base Kit B.

Outcome measures

Outcome measures
Measure	Clopridogrel n=41 Participants The subjects received clopidogrel 75 mg PO qd for the first 6 weeks or received clopidogrel 75 mg PO qd for the last 6 weeks.	Placebo n=41 Participants The subjects received placebo PO qd for the first 6 weeks or the subjects received placebo PO qd for the last 6 weeks.
Inflammatory Marker CD40 Ligand	1202.21 pg/mL Standard Error 318.35	2169.32 pg/mL Standard Error 318.35

Adverse Events

Clopidogrel

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

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

Dr. Arshed Quyyumi

Emory University

Phone: 404-727-3655

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place