Trial Outcomes & Findings for Atorvastatin to Treat Pulmonary Sarcoidosis (NCT NCT00279708)
NCT ID: NCT00279708
Last Updated: 2017-05-22
Results Overview
The duration of steroid sparing was defined as the date when the target dose of prednisone was reached until the date at which the dose was increased and/or met the relapse (flare) criteria; or until the 12 month study phase ended if no prednisone dose increase was required. The steroid sparing period was measured in units of days. The prednisone target dose was defined as a 90% reduction of the baseline dose or an absolute prednisone dose of 4 mg/day or less.
COMPLETED
PHASE2
55 participants
1 year
2017-05-22
Participant Flow
Subjects were recruited by national advertising (self-referrals), physician referrals, and through a medical clinic sponsored by the NIH, from March 2006 through March 2015.
Subjects were screened by telephone and later during clinical testing a evaluation at the NIH Clinical Center. During this time subjects were evaluated to determine if they met the enrollment criteria, including that of treatment requiring disease, and relatively stable dosing prior to entry.
Participant milestones
| Measure |
Intervention Group (Atorvastatin)
Atorvastatin Subjects were assigned to the treatment intervention by way of double blind masking. Atorvastatin 80 mg/day was the initial treatment given, as tolerated for a 12 month period. During the study, a 50% dose reduction was applied for subjects meeting pre-specified criteria.
|
Control Group (Placebo)
Placebo In a double-blind fashion, subjects were assigned to receive the sham intervention which appeared the same as the intervention agent. For subjects meeting pre-specified criteria, a 50% dose reduction was applied during the 12 month treatment phase of the study.
|
|---|---|---|
|
Overall Study
STARTED
|
27
|
28
|
|
Overall Study
COMPLETED
|
24
|
24
|
|
Overall Study
NOT COMPLETED
|
3
|
4
|
Reasons for withdrawal
| Measure |
Intervention Group (Atorvastatin)
Atorvastatin Subjects were assigned to the treatment intervention by way of double blind masking. Atorvastatin 80 mg/day was the initial treatment given, as tolerated for a 12 month period. During the study, a 50% dose reduction was applied for subjects meeting pre-specified criteria.
|
Control Group (Placebo)
Placebo In a double-blind fashion, subjects were assigned to receive the sham intervention which appeared the same as the intervention agent. For subjects meeting pre-specified criteria, a 50% dose reduction was applied during the 12 month treatment phase of the study.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
2
|
3
|
|
Overall Study
Adverse Event
|
1
|
1
|
Baseline Characteristics
Atorvastatin to Treat Pulmonary Sarcoidosis
Baseline characteristics by cohort
| Measure |
Intervention Group (Atorvastatin)
n=27 Participants
Atorvastatin: Subjects were assigned to the treatment intervention by way of double blind masking. Atorvastatin 80 mg/day was the initial treatment given, as tolerated for a 12 month period. During the study, a 50% dose reduction was applied for subjects meeting pre-specified criteria.
|
Control Group (Placebo)
n=28 Participants
Placebo: In a double-blind fashion, subjects were assigned to receive the sham intervention which appeared the same as the intervention agent. For subjects meeting pre-specified criteria, a 50% dose reduction was applied during the 12 month treatment phase of the study.
|
Total
n=55 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
|
26 Participants
n=5 Participants
|
28 Participants
n=7 Participants
|
54 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Age, Continuous
|
48.9 years
STANDARD_DEVIATION 7.95 • n=5 Participants
|
46.8 years
STANDARD_DEVIATION 9.12 • n=7 Participants
|
47.8 years
STANDARD_DEVIATION 8.57 • n=5 Participants
|
|
Sex: Female, Male
Female
|
17 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
33 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
27 participants
n=5 Participants
|
28 participants
n=7 Participants
|
55 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 1 yearThe duration of steroid sparing was defined as the date when the target dose of prednisone was reached until the date at which the dose was increased and/or met the relapse (flare) criteria; or until the 12 month study phase ended if no prednisone dose increase was required. The steroid sparing period was measured in units of days. The prednisone target dose was defined as a 90% reduction of the baseline dose or an absolute prednisone dose of 4 mg/day or less.
Outcome measures
| Measure |
Intervention Group (Atorvastatin)
n=27 Participants
Atorvastatin: Subjects were assigned to the treatment intervention by way of double blind masking. Atorvastatin 80 mg/day was the initial treatment given, as tolerated for a 12 month period. During the study, a 50% dose reduction was applied for subjects meeting pre-specified criteria.
|
Control Group (Placebo)
n=28 Participants
Placebo: In a double-blind fashion, subjects were assigned to receive the sham intervention which appeared the same as the intervention agent. For subjects meeting pre-specified criteria, a 50% dose reduction was applied during the 12 month treatment phase of the study: Placebo vs. Atorvastatin
|
|---|---|---|
|
The Steroid Sparing Period
|
301 days
Interval 2.0 to 315.0
|
257 days
Interval 152.0 to 322.0
|
SECONDARY outcome
Timeframe: 1 yearFlare rates and relative risk: Flares (relapses) were defined as the physiological deterioration in pulmonary function due to worsened pulmonary inflammation. The criteria used for a pulmonary flare included: \> 15% decline in static function (FEV1 post, FVC post); or (\> 20% DLCO adj); or a \> 15% decline in walk distance as measured by the six minute walk test, or via a decline in oxygen consumption collected during a cardiopulmonary exercise test (CPET). Additional factors considered included an increase in dyspnea (\>15% increase in the dyspnea scale (TDI); and/or significant radiographic worsening. Clinical assessment of the patient's status may have been factored into the criteria for flare determination as well.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 12 month treatment periodSpirometry measurements (FVC and FEV1) obtained post-bronchodilator Diffusion, adjusted for hemoglobin
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 12 month treatment periodCardiopulmonary Exercise Tests (VO2 peak, VO2/work, VECO2) Six minute Walk Test (distance, Borg scale)
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 12 month treatment periodSt. George's Respiratory Questionnaire SF-36 Modified MRC Dyspnea Scale
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 12 month treatment periodHRCT Chest radiographs
Outcome measures
Outcome data not reported
Adverse Events
Intervention Group (Atorvastatin)
Control Group (Placebo)
Serious adverse events
| Measure |
Intervention Group (Atorvastatin)
n=27 participants at risk
Atorvastatin: Subjects were assigned to the treatment intervention by way of double blind masking. Atorvastatin 80 mg/day was the initial treatment given, as tolerated for a 12 month period. During the study, a 50% dose reduction was applied for subjects meeting pre-specified criteria.
|
Control Group (Placebo)
n=28 participants at risk
Placebo: In a double-blind fashion, subjects were assigned to receive the sham intervention which appeared the same as the intervention agent. For subjects meeting pre-specified criteria, a 50% dose reduction was applied during the 12 month treatment phase of the study.
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
11.1%
3/27 • Number of events 3 • 12 months
|
3.6%
1/28 • Number of events 1 • 12 months
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness
|
0.00%
0/27 • 12 months
|
3.6%
1/28 • Number of events 1 • 12 months
|
|
Musculoskeletal and connective tissue disorders
Avascular Necrosis
|
3.7%
1/27 • Number of events 1 • 12 months
|
0.00%
0/28 • 12 months
|
|
Gastrointestinal disorders
Appendicitis
|
3.7%
1/27 • Number of events 1 • 12 months
|
0.00%
0/28 • 12 months
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
0.00%
0/27 • 12 months
|
3.6%
1/28 • Number of events 1 • 12 months
|
|
Hepatobiliary disorders
Aspartate Aminotransferase elevation
|
3.7%
1/27 • Number of events 1 • 12 months
|
3.6%
1/28 • Number of events 1 • 12 months
|
|
Investigations
Alanine aminotransferase elevation
|
3.7%
1/27 • Number of events 1 • 12 months
|
0.00%
0/28 • 12 months
|
|
Musculoskeletal and connective tissue disorders
Aldolase increased
|
0.00%
0/27 • 12 months
|
3.6%
1/28 • Number of events 1 • 12 months
|
|
Investigations
Creatinine Phosphokinase Increase
|
0.00%
0/27 • 12 months
|
3.6%
1/28 • Number of events 1 • 12 months
|
|
Vascular disorders
Deep Venous Thrombosis
|
3.7%
1/27 • Number of events 1 • 12 months
|
0.00%
0/28 • 12 months
|
|
Respiratory, thoracic and mediastinal disorders
Diffusion of carbon monoxide
|
0.00%
0/27 • 12 months
|
3.6%
1/28 • Number of events 1 • 12 months
|
|
Endocrine disorders
Hypoglycemia
|
0.00%
0/27 • 12 months
|
7.1%
2/28 • Number of events 2 • 12 months
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
7.4%
2/27 • Number of events 2 • 12 months
|
0.00%
0/28 • 12 months
|
|
Investigations
Myoglobin Increase
|
0.00%
0/27 • 12 months
|
3.6%
1/28 • Number of events 1 • 12 months
|
|
Respiratory, thoracic and mediastinal disorders
Obstructive Sleep Apnea
|
0.00%
0/27 • 12 months
|
3.6%
1/28 • Number of events 1 • 12 months
|
|
Musculoskeletal and connective tissue disorders
Rhabdomyolysis
|
0.00%
0/27 • 12 months
|
3.6%
1/28 • Number of events 1 • 12 months
|
|
Cardiac disorders
Sinus Bradycardia
|
0.00%
0/27 • 12 months
|
3.6%
1/28 • Number of events 1 • 12 months
|
|
Infections and infestations
Temperature Elevation
|
3.7%
1/27 • Number of events 1 • 12 months
|
0.00%
0/28 • 12 months
|
|
Skin and subcutaneous tissue disorders
Pruritis
|
3.7%
1/27 • Number of events 1 • 12 months
|
0.00%
0/28 • 12 months
|
|
Musculoskeletal and connective tissue disorders
Muscle Weakness unilateral
|
0.00%
0/27 • 12 months
|
3.6%
1/28 • Number of events 1 • 12 months
|
|
Musculoskeletal and connective tissue disorders
Numbness
|
0.00%
0/27 • 12 months
|
3.6%
1/28 • Number of events 1 • 12 months
|
|
Musculoskeletal and connective tissue disorders
Pain
|
0.00%
0/27 • 12 months
|
3.6%
1/28 • Number of events 1 • 12 months
|
Other adverse events
| Measure |
Intervention Group (Atorvastatin)
n=27 participants at risk
Atorvastatin: Subjects were assigned to the treatment intervention by way of double blind masking. Atorvastatin 80 mg/day was the initial treatment given, as tolerated for a 12 month period. During the study, a 50% dose reduction was applied for subjects meeting pre-specified criteria.
|
Control Group (Placebo)
n=28 participants at risk
Placebo: In a double-blind fashion, subjects were assigned to receive the sham intervention which appeared the same as the intervention agent. For subjects meeting pre-specified criteria, a 50% dose reduction was applied during the 12 month treatment phase of the study.
|
|---|---|---|
|
Investigations
Aldolase Increase
|
7.4%
2/27 • Number of events 2 • 12 months
|
10.7%
3/28 • Number of events 3 • 12 months
|
|
Investigations
ACE Level increased
|
7.4%
2/27 • Number of events 2 • 12 months
|
3.6%
1/28 • Number of events 1 • 12 months
|
|
Investigations
Alkaline Phosphatase Increase
|
11.1%
3/27 • Number of events 3 • 12 months
|
3.6%
1/28 • Number of events 1 • 12 months
|
|
Investigations
Alanine aminotransferase Increased
|
48.1%
13/27 • Number of events 13 • 12 months
|
14.3%
4/28 • Number of events 4 • 12 months
|
|
Investigations
Asparatate aminotransferase Increased
|
51.9%
14/27 • Number of events 14 • 12 months
|
17.9%
5/28 • Number of events 5 • 12 months
|
|
Investigations
Amylase Increased
|
0.00%
0/27 • 12 months
|
14.3%
4/28 • Number of events 4 • 12 months
|
|
Respiratory, thoracic and mediastinal disorders
Bronchial Infection
|
0.00%
0/27 • 12 months
|
7.1%
2/28 • Number of events 2 • 12 months
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasm
|
7.4%
2/27 • Number of events 2 • 12 months
|
0.00%
0/28 • 12 months
|
|
Investigations
Creatine Phosphokinase increased
|
7.4%
2/27 • Number of events 2 • 12 months
|
10.7%
3/28 • Number of events 3 • 12 months
|
|
Investigations
Creatinine increased
|
0.00%
0/27 • 12 months
|
14.3%
4/28 • Number of events 4 • 12 months
|
|
Respiratory, thoracic and mediastinal disorders
Diffusion of Carbon Monoxide decreased
|
7.4%
2/27 • Number of events 2 • 12 months
|
14.3%
4/28 • Number of events 4 • 12 months
|
|
Vascular disorders
Hypotension
|
0.00%
0/27 • 12 months
|
7.1%
2/28 • Number of events 2 • 12 months
|
|
Investigations
Lipase Increase
|
3.7%
1/27 • Number of events 1 • 12 months
|
7.1%
2/28 • Number of events 2 • 12 months
|
|
Infections and infestations
Urinary Tract Infection
|
0.00%
0/27 • 12 months
|
7.1%
2/28 • Number of events 2 • 12 months
|
Additional Information
Joseph Fontana, MD
The National Institutes of Health/ The National Heart, Lung, and Blood Institute
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place