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Atorvastatin to Treat Pulmonary Sarcoidosis

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ClinicalTrials.gov Identifier: NCT00279708
Recruitment Status : Completed
First Posted : January 19, 2006
Results First Posted : August 12, 2016
Last Update Posted : May 22, 2017
Sponsor:
Information provided by (Responsible Party):
Joseph R. Fontana, M.D., National Heart, Lung, and Blood Institute (NHLBI)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Sarcoidosis, Pulmonary
Interventions Drug: Atorvastatin
Other: Placebo Oral Tablet
Enrollment 55
Recruitment Details 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.
Pre-assignment Details 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.
Arm/Group Title Intervention Group (Atorvastatin) Control Group (Placebo)
Hide Arm/Group Description 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. 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.
Period Title: Overall Study
Started 27 [1] 28
Completed 24 24
Not Completed 3 4
Reason Not Completed
Withdrawal by Subject             2             3
Adverse Event             1             1
[1]
"Started" meaning randomized
Arm/Group Title Intervention Group (Atorvastatin) Control Group (Placebo) Total
Hide Arm/Group Description 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. 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 of all reporting groups
Overall Number of Baseline Participants 27 28 55
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 27 participants 28 participants 55 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
26
  96.3%
28
 100.0%
54
  98.2%
>=65 years
1
   3.7%
0
   0.0%
1
   1.8%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 27 participants 28 participants 55 participants
48.9  (7.95) 46.8  (9.12) 47.8  (8.57)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 27 participants 28 participants 55 participants
Female
17
  63.0%
16
  57.1%
33
  60.0%
Male
10
  37.0%
12
  42.9%
22
  40.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 27 participants 28 participants 55 participants
27 28 55
1.Primary Outcome
Title The Steroid Sparing Period
Hide Description 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.
Time Frame 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Intervention Group (Atorvastatin) Control Group (Placebo)
Hide Arm/Group Description:
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.
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
Overall Number of Participants Analyzed 27 28
Mean (Inter-Quartile Range)
Unit of Measure: days
301
(2 to 315)
257
(152 to 322)
2.Secondary Outcome
Title Pulmonary Sarcoidosis Flares
Hide Description Flare 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.
Time Frame 1 year
Outcome Measure Data Not Reported
3.Secondary Outcome
Title Pulmonary Function Tests
Hide Description Spirometry measurements (FVC and FEV1) obtained post-bronchodilator Diffusion, adjusted for hemoglobin
Time Frame 12 month treatment period
Outcome Measure Data Not Reported
4.Secondary Outcome
Title Exercise Performance
Hide Description Cardiopulmonary Exercise Tests (VO2 peak, VO2/work, VECO2) Six minute Walk Test (distance, Borg scale)
Time Frame 12 month treatment period
Outcome Measure Data Not Reported
5.Secondary Outcome
Title Quality of Life and Dyspnea Scales
Hide Description St. George's Respiratory Questionnaire SF-36 Modified MRC Dyspnea Scale
Time Frame 12 month treatment period
Outcome Measure Data Not Reported
6.Other Pre-specified Outcome
Title Chest Imaging
Hide Description HRCT Chest radiographs
Time Frame 12 month treatment period
Outcome Measure Data Not Reported
Time Frame 12 months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Intervention Group (Atorvastatin) Control Group (Placebo)
Hide Arm/Group Description 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. 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.
All-Cause Mortality
Intervention Group (Atorvastatin) Control Group (Placebo)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Intervention Group (Atorvastatin) Control Group (Placebo)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   12/27 (44.44%)      16/28 (57.14%)    
Cardiac disorders     
Sinus Bradycardia  1  0/27 (0.00%)  0 1/28 (3.57%)  1
Endocrine disorders     
Hypoglycemia  1  0/27 (0.00%)  0 2/28 (7.14%)  2
Gastrointestinal disorders     
Appendicitis * 1  1/27 (3.70%)  1 0/28 (0.00%)  0
Hepatobiliary disorders     
Aspartate Aminotransferase elevation  1  1/27 (3.70%)  1 1/28 (3.57%)  1
Infections and infestations     
Temperature Elevation  1  1/27 (3.70%)  1 0/28 (0.00%)  0
Investigations     
Alanine aminotransferase elevation  1  1/27 (3.70%)  1 0/28 (0.00%)  0
Creatinine Phosphokinase Increase  1  0/27 (0.00%)  0 1/28 (3.57%)  1
Myoglobin Increase  1 [1]  0/27 (0.00%)  0 1/28 (3.57%)  1
Musculoskeletal and connective tissue disorders     
Muscle weakness * 1  0/27 (0.00%)  0 1/28 (3.57%)  1
Avascular Necrosis * 1  1/27 (3.70%)  1 0/28 (0.00%)  0
Arthritis * 1  0/27 (0.00%)  0 1/28 (3.57%)  1
Aldolase increased  1  0/27 (0.00%)  0 1/28 (3.57%)  1
Rhabdomyolysis  1  0/27 (0.00%)  0 1/28 (3.57%)  1
Muscle Weakness unilateral * 1  0/27 (0.00%)  0 1/28 (3.57%)  1
Numbness * 1  0/27 (0.00%)  0 1/28 (3.57%)  1
Pain * 1  0/27 (0.00%)  0 1/28 (3.57%)  1
Respiratory, thoracic and mediastinal disorders     
Pneumonia * 1  3/27 (11.11%)  3 1/28 (3.57%)  1
Diffusion of carbon monoxide  1  0/27 (0.00%)  0 1/28 (3.57%)  1
Hypoxia  1  2/27 (7.41%)  2 0/28 (0.00%)  0
Obstructive Sleep Apnea * 1  0/27 (0.00%)  0 1/28 (3.57%)  1
Skin and subcutaneous tissue disorders     
Pruritis * 1  1/27 (3.70%)  1 0/28 (0.00%)  0
Vascular disorders     
Deep Venous Thrombosis * 1  1/27 (3.70%)  1 0/28 (0.00%)  0
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, CTCAE (4.0)
[1]
Rhabdomyolysis
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Intervention Group (Atorvastatin) Control Group (Placebo)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   16/27 (59.26%)      12/28 (42.86%)    
Infections and infestations     
Urinary Tract Infection * 1  0/27 (0.00%)  0 2/28 (7.14%)  2
Investigations     
Aldolase Increase * 1  2/27 (7.41%)  2 3/28 (10.71%)  3
ACE Level increased  1  2/27 (7.41%)  2 1/28 (3.57%)  1
Alkaline Phosphatase Increase * 1  3/27 (11.11%)  3 1/28 (3.57%)  1
Alanine aminotransferase Increased  1  13/27 (48.15%)  13 4/28 (14.29%)  4
Asparatate aminotransferase Increased  1  14/27 (51.85%)  14 5/28 (17.86%)  5
Amylase Increased  1  0/27 (0.00%)  0 4/28 (14.29%)  4
Creatine Phosphokinase increased  1  2/27 (7.41%)  2 3/28 (10.71%)  3
Creatinine increased  1  0/27 (0.00%)  0 4/28 (14.29%)  4
Lipase Increase * 1  1/27 (3.70%)  1 2/28 (7.14%)  2
Respiratory, thoracic and mediastinal disorders     
Bronchial Infection * 1  0/27 (0.00%)  0 2/28 (7.14%)  2
Bronchospasm  1  2/27 (7.41%)  2 0/28 (0.00%)  0
Diffusion of Carbon Monoxide decreased  1  2/27 (7.41%)  2 4/28 (14.29%)  4
Vascular disorders     
Hypotension * 1  0/27 (0.00%)  0 2/28 (7.14%)  2
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, CTCAE (4.0)
The recruitment goal of 96 subjects was not met due to slow accrual. The primary endpoint analysis was based on the available subject data.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Joseph Fontana, MD
Organization: The National Institutes of Health/ The National Heart, Lung, and Blood Institute
Phone: 301-451-7740
EMail: fontanaj@nhlbi.nih.gov
Layout table for additonal information
Responsible Party: Joseph R. Fontana, M.D., National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier: NCT00279708     History of Changes
Other Study ID Numbers: 060072
06-H-0072 ( Other Identifier: NIH NHLBI )
First Submitted: January 18, 2006
First Posted: January 19, 2006
Results First Submitted: June 30, 2016
Results First Posted: August 12, 2016
Last Update Posted: May 22, 2017