Trial Outcomes & Findings for Clinical Utility of Endothelial Dysfunction in PAD (NCT NCT00491751)

Results Overview

Change in flow mediated dilation with treatment: FMD visit 2 - FMD visit 1 FMD is measured by using vascular ultrasound to determine the baseline diameter of the brachial artery. Endothelium-dependent vasodilation is induced by 5-minute arterial occlusion with a blood pressure cuff. When the cuff is released, the resultant increase in blood flow (reactive hyperemia) stimulates vasodilation of the brachial artery. This flow-mediated dilation (FMD) is expressed as the percent change from baseline. Healthy individuals typical dysplay a 10 to 12% dilation. Individuals with PAD had markedly impaired dilation of 6-7. The currernt study sought to determine whether a change in FMD would occur following intervention.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

108 participants

Primary outcome timeframe

1-4 weeks

Results posted on

2018-07-27

Participant Flow

Recruitment: May 2004 to June 2010.

Participant milestones

Participant milestones
Measure	Atorvastatin Atorvastatin 40 or 80 mg	Ascorbic Acid Ascorbic Acid 500 mg per day	Placebo Placebo atorvastatin and Placebo ascorbic acid
Overall Study STARTED	22	44	42
Overall Study COMPLETED	22	44	42
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Clinical Utility of Endothelial Dysfunction in PAD

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Atorvastatin n=22 Participants Atorvastatin 40 or 80 mg	Ascorbic Acid n=44 Participants Ascorbic Acid 500 mg per day	Placebo n=42 Participants Placebo atorvastatin and Placebo ascorbic acid	Total n=108 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	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	11 Participants n=5 Participants	22 Participants n=7 Participants	21 Participants n=5 Participants	54 Participants n=4 Participants
Age, Categorical >=65 years	11 Participants n=5 Participants	22 Participants n=7 Participants	21 Participants n=5 Participants	54 Participants n=4 Participants
Age, Continuous	68 years STANDARD_DEVIATION 11 • n=5 Participants	66 years STANDARD_DEVIATION 8 • n=7 Participants	65 years STANDARD_DEVIATION 9 • n=5 Participants	66 years STANDARD_DEVIATION 9 • n=4 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	14 Participants n=7 Participants	6 Participants n=5 Participants	29 Participants n=4 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	30 Participants n=7 Participants	36 Participants n=5 Participants	79 Participants n=4 Participants
Region of Enrollment United States	22 participants n=5 Participants	44 participants n=7 Participants	42 participants n=5 Participants	108 participants n=4 Participants

PRIMARY outcome

Timeframe: 1-4 weeks

Population: All enrolled subjects were analyzed.

Change in flow mediated dilation with treatment: FMD visit 2 - FMD visit 1 FMD is measured by using vascular ultrasound to determine the baseline diameter of the brachial artery. Endothelium-dependent vasodilation is induced by 5-minute arterial occlusion with a blood pressure cuff. When the cuff is released, the resultant increase in blood flow (reactive hyperemia) stimulates vasodilation of the brachial artery. This flow-mediated dilation (FMD) is expressed as the percent change from baseline. Healthy individuals typical dysplay a 10 to 12% dilation. Individuals with PAD had markedly impaired dilation of 6-7. The currernt study sought to determine whether a change in FMD would occur following intervention.

Outcome measures

Outcome measures
Measure	Atorvastatin n=22 Participants Atorvastatin 40 or 80 mg	Ascorbic Acid n=44 Participants Ascorbic Acid 500 mg per day	Placebo n=42 Participants Placebo atorvastatin and Placebo ascorbic acid
Change in FMD	0.88 percent change of FMD Standard Deviation 3.0	0.41 percent change of FMD Standard Deviation 3.6	0.88 percent change of FMD Standard Deviation 3.5

SECONDARY outcome

Timeframe: 2 months

Population: For this outcome all participants were stratified into 2 groups: those with, and those without a CVD event (not by treatment group)

This outcome is independent of the treatment group so the groups are 'CVD event' and ' No CVD Event'. Cardiovascular events (CVD) included cardiovascular disease, myocardial infarction, congestive heart failure, stroke, and unstable angina.

Outcome measures

Outcome measures
Measure	Atorvastatin n=16 Participants Atorvastatin 40 or 80 mg	Ascorbic Acid n=92 Participants Ascorbic Acid 500 mg per day	Placebo Placebo atorvastatin and Placebo ascorbic acid
Percentage Change in FMD in All Participants With and Without a CVD Event (Not by Treatment Group)	0.5 percent change of flow-mediated dilation Standard Deviation 4.0	0.7 percent change of flow-mediated dilation Standard Deviation 3.4	—

Adverse Events

Atorvastatin

Serious events: 3 serious events

Other events: 0 other events

Deaths: 0 deaths

Ascorbic Acid

Serious events: 6 serious events

Other events: 0 other events

Deaths: 1 deaths

Placebo

Serious events: 7 serious events

Other events: 0 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Atorvastatin n=22 participants at risk Atorvastatin 40 or 80 mg	Ascorbic Acid n=44 participants at risk Ascorbi acid 500 mg \[per day	Placebo n=42 participants at risk Placebo for atorvastatin and ascorbic acid
Cardiac disorders Myocardial infaction	9.1% 2/22 • 2 months All subjects were followed for 2 months. They were questioned about adverse events and medical records were reviewed.	4.5% 2/44 • 2 months All subjects were followed for 2 months. They were questioned about adverse events and medical records were reviewed.	14.3% 6/42 • 2 months All subjects were followed for 2 months. They were questioned about adverse events and medical records were reviewed.
Cardiac disorders Unstable angina	0.00% 0/22 • 2 months All subjects were followed for 2 months. They were questioned about adverse events and medical records were reviewed.	0.00% 0/44 • 2 months All subjects were followed for 2 months. They were questioned about adverse events and medical records were reviewed.	7.1% 3/42 • 2 months All subjects were followed for 2 months. They were questioned about adverse events and medical records were reviewed.
Cardiac disorders Congestive heart failure	0.00% 0/22 • 2 months All subjects were followed for 2 months. They were questioned about adverse events and medical records were reviewed.	4.5% 2/44 • 2 months All subjects were followed for 2 months. They were questioned about adverse events and medical records were reviewed.	4.8% 2/42 • 2 months All subjects were followed for 2 months. They were questioned about adverse events and medical records were reviewed.
Nervous system disorders CVA/TIA	9.1% 2/22 • 2 months All subjects were followed for 2 months. They were questioned about adverse events and medical records were reviewed.	4.5% 2/44 • 2 months All subjects were followed for 2 months. They were questioned about adverse events and medical records were reviewed.	0.00% 0/42 • 2 months All subjects were followed for 2 months. They were questioned about adverse events and medical records were reviewed.
Cardiac disorders Venticular fibrillation	0.00% 0/22 • 2 months All subjects were followed for 2 months. They were questioned about adverse events and medical records were reviewed.	0.00% 0/44 • 2 months All subjects were followed for 2 months. They were questioned about adverse events and medical records were reviewed.	2.4% 1/42 • 2 months All subjects were followed for 2 months. They were questioned about adverse events and medical records were reviewed.
Cardiac disorders Other CVD event	4.5% 1/22 • 2 months All subjects were followed for 2 months. They were questioned about adverse events and medical records were reviewed.	6.8% 3/44 • 2 months All subjects were followed for 2 months. They were questioned about adverse events and medical records were reviewed.	7.1% 3/42 • 2 months All subjects were followed for 2 months. They were questioned about adverse events and medical records were reviewed.

Other adverse events

Adverse event data not reported

Additional Information

Naomi M. Hamburg, MD

Boston University School of Medicine

Phone: 617-638-7462

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place