Trial Outcomes & Findings for Atorvastatin for Microvascular Endothelial Function and Raynaud in Early Diffuse Scleroderma (NCT NCT02370784)
NCT ID: NCT02370784
Last Updated: 2020-08-12
Results Overview
EndoPAT is a proprietary device that assesses digital (microvascular) endothelial function during reactive hyperemia. A probe is placed on both index fingers. After 5 minutes of baseline observation, one arm is occluded for 5 minutes, while the other is not and serves as control. Output is the reactive hyperemia index (RHI), calculated as the post-to-pre occlusion signal ratio in the occluded side, "normalized to the control side and further corrected for baseline vascular tone" per Itamar Medical. There are no units. RHI ≤ 1.67 is abnormal and indicates endothelial dysfunction.
COMPLETED
PHASE2
24 participants
Change in RHI from baseline to 16 weeks expressed as the percentage of patients who improve (respond).
2020-08-12
Participant Flow
Patients were recruited at a single Scleroderma Center between March 2015 and August 2017.
Participant milestones
| Measure |
Atorvastatin 40 mg Daily
Length of intervention: 16 weeks atorvastatin: Atorvastatin is an oral cholesterol-lowering medication commonly referred to as statin therapy.
|
Placebo Control
Placebo: oral drug of similar appearance to atorvastatin
|
|---|---|---|
|
Overall Study
STARTED
|
10
|
14
|
|
Overall Study
COMPLETED
|
10
|
13
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
Reasons for withdrawal
| Measure |
Atorvastatin 40 mg Daily
Length of intervention: 16 weeks atorvastatin: Atorvastatin is an oral cholesterol-lowering medication commonly referred to as statin therapy.
|
Placebo Control
Placebo: oral drug of similar appearance to atorvastatin
|
|---|---|---|
|
Overall Study
Patient started prohibited medication
|
0
|
1
|
Baseline Characteristics
Atorvastatin for Microvascular Endothelial Function and Raynaud in Early Diffuse Scleroderma
Baseline characteristics by cohort
| Measure |
Atorvastatin 40 mg Daily
n=10 Participants
Atorvastatin 40 mg daily x 16 weeks
|
Placebo
n=14 Participants
Placebo daily x 16 weeks
|
Total
n=24 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
50.0 years
STANDARD_DEVIATION 13.9 • n=5 Participants
|
55.7 years
STANDARD_DEVIATION 5.3 • n=7 Participants
|
53.3 years
STANDARD_DEVIATION 10.7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White, non-hispanic
|
8 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
African-American
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
History of hyperlipidemia
|
4 participants
n=5 Participants
|
2 participants
n=7 Participants
|
6 participants
n=5 Participants
|
|
History of hypertension
|
1 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Obesity
|
2 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Family history of early cardiovascular disease
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
mean modified Rodnan skin score
|
18.9 points
STANDARD_DEVIATION 9.6 • n=5 Participants
|
22.8 points
STANDARD_DEVIATION 8.9 • n=7 Participants
|
21.3 points
STANDARD_DEVIATION 9.2 • n=5 Participants
|
|
Mean EndoPAT reactive hyperemia index (RHI)
|
1.36 units
STANDARD_DEVIATION 0.36 • n=5 Participants
|
1.85 units
STANDARD_DEVIATION 1.20 • n=7 Participants
|
1.46 units
STANDARD_DEVIATION 0.96 • n=5 Participants
|
|
Raynaud condition score (median, IQR)
|
5.0 units on a scale
n=5 Participants
|
2.0 units on a scale
n=7 Participants
|
2.5 units on a scale
n=5 Participants
|
|
Raynaud symptom severity assessed by visual analog scale
|
4.0 units on a scale
n=5 Participants
|
1.5 units on a scale
n=7 Participants
|
2.3 units on a scale
n=5 Participants
|
|
Brachial % flow mediated dilation (%FMD)
|
11.3 %
n=5 Participants
|
10.3 %
n=7 Participants
|
10.3 %
n=5 Participants
|
PRIMARY outcome
Timeframe: Change in RHI from baseline to 16 weeks expressed as the percentage of patients who improve (respond).Population: The patient who did not complete the study had his data analyzed using last observation carried forward. Improvement was defined as an increase in the RHI from baseline to 16 weeks. Non-responders were defined as no change or worsening (decrease) in the RHI at 16 weeks. Results are expressed as a percentage
EndoPAT is a proprietary device that assesses digital (microvascular) endothelial function during reactive hyperemia. A probe is placed on both index fingers. After 5 minutes of baseline observation, one arm is occluded for 5 minutes, while the other is not and serves as control. Output is the reactive hyperemia index (RHI), calculated as the post-to-pre occlusion signal ratio in the occluded side, "normalized to the control side and further corrected for baseline vascular tone" per Itamar Medical. There are no units. RHI ≤ 1.67 is abnormal and indicates endothelial dysfunction.
Outcome measures
| Measure |
Active Drug
n=10 Participants
atorvastatin 40 mg once daily for sixteen weeks
atorvastatin: Atorvastatin is an oral cholesterol-lowering medication commonly referred to as statin therapy.
|
Placebo Control
n=14 Participants
receive a placebo of similar appearance once daily for sixteen weeks
Placebo: oral drug of similar appearance to atorvastatin
|
|---|---|---|
|
Proportion of Patients Improving Their EndoPAT Reactive Hyperemia Index (RHI) at the End-of-study (16 Weeks)
|
6 Participants
|
4 Participants
|
SECONDARY outcome
Timeframe: change in RCS from baseline to week 16The Raynaud Condition Score is a patient-reported outcome of a single question regarding Raynaud severity. It is a visual analog scale with a results range of 0-100. A score of 0 us is no symptoms, and 100 severe symptoms. It is recommended by OMERACT for assessment of Raynaud phenomenon.
Outcome measures
| Measure |
Active Drug
n=10 Participants
atorvastatin 40 mg once daily for sixteen weeks
atorvastatin: Atorvastatin is an oral cholesterol-lowering medication commonly referred to as statin therapy.
|
Placebo Control
n=14 Participants
receive a placebo of similar appearance once daily for sixteen weeks
Placebo: oral drug of similar appearance to atorvastatin
|
|---|---|---|
|
Change in the Raynaud Condition Score (RCS) at 16 Weeks (End-of-study) From Baseline
|
-2.0 score on a scale
Interval -2.0 to 0.0
|
0 score on a scale
Interval -1.0 to 1.0
|
SECONDARY outcome
Timeframe: baseline to 16 weeksThe RP-VAS scale measure ranges from 0-100, with 0 being no symptoms and 100 severe symptoms. Reported is the median and interquartile range of change between baseline and week 16 (end-of-study).
Outcome measures
| Measure |
Active Drug
n=10 Participants
atorvastatin 40 mg once daily for sixteen weeks
atorvastatin: Atorvastatin is an oral cholesterol-lowering medication commonly referred to as statin therapy.
|
Placebo Control
n=14 Participants
receive a placebo of similar appearance once daily for sixteen weeks
Placebo: oral drug of similar appearance to atorvastatin
|
|---|---|---|
|
The Median Change in the Raynaud Phenomenon Visual Analog Scale (RP-VAS) Score at 16 Weeks (End-of-study) Compared to Baseline in the Atorvastatin and Placebo Groups.
|
0.5 score on a scale
Interval -1.5 to 6.0
|
0.0 score on a scale
Interval -1.0 to 1.5
|
SECONDARY outcome
Timeframe: baseline to 16 weeksPopulation: For the patient with a SAE, data was treated as last observation carried forward
%FMD = change in brachial artery flow-mediation dilation between pre and post-ischemia. Baseline (pre-ischemia) is the reference to which percentage change is calculated. Result is expressed as the % of patients who had an improvement in their %FMD at 16 weeks compared to baseline.
Outcome measures
| Measure |
Active Drug
n=10 Participants
atorvastatin 40 mg once daily for sixteen weeks
atorvastatin: Atorvastatin is an oral cholesterol-lowering medication commonly referred to as statin therapy.
|
Placebo Control
n=14 Participants
receive a placebo of similar appearance once daily for sixteen weeks
Placebo: oral drug of similar appearance to atorvastatin
|
|---|---|---|
|
% of Patients Who Improved Their Brachial Flow-mediation Dilation (%FMD) at 16 Weeks
|
5 Participants
|
5 Participants
|
Adverse Events
Atorvastatin 40 mg Daily
Placebo Control
Serious adverse events
| Measure |
Atorvastatin 40 mg Daily
n=10 participants at risk
Length of intervention: 16 weeks atorvastatin: Atorvastatin is an oral cholesterol-lowering medication commonly referred to as statin therapy.
|
Placebo Control
n=14 participants at risk
Placebo: oral drug of similar appearance to atorvastatin
|
|---|---|---|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Esophageal cancer
|
0.00%
0/10 • 16 weeks plus 30 days after the end of intervention
|
7.1%
1/14 • Number of events 1 • 16 weeks plus 30 days after the end of intervention
|
Other adverse events
Adverse event data not reported
Additional Information
Robyn T. Domsic, MD MPH
University of Pittsburgh School of Medicine
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place