Atorvastatin to Treat Pulmonary Sarcoidosis

NCT00279708 | Completed Phase 2 Results DMC

• 2 other identifiers: 06007206-H-0072
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

This study will determine if atorvastatin (Lipitor) can help patients with pulmonary (lung) sarcoidosis and replace or reduce the need for patients to take steroids, such as prednisone. Sarcoidosis is an inflammatory disease that can affect nearly any part of the body. Pulmonary sarcoidosis may resolve on its own or it may progress to irreversible lung damage, disability, and death. Many sarcoidosis patients are treated with prednisone, but the drug is not effective in all patients, and it can cause serious side effects, such as high blood pressure, sugar diabetes, eye cataracts, and bone thinning. Patients with stage II or III pulmonary sarcoidosis between 18 and 70 years of age who require prednisone may be eligible for this study. Candidates are screened with the tests and procedures described below. Participants are randomly assigned to one of two treatment groups: one group takes atorvastatin; the other takes a placebo (a look-alike pill that has no active ingredient to fight sarcoidosis). Both groups take the pills by mouth once a day for 12 months. When treatment begins, participants begin to have their prednisone dosage tapered (reduced). The tapering is done over 8 weeks until the dose is reduced by 90 percent. Patients are evaluated periodically to determine if the two groups differ in how long they can remain on the reduced dose of prednisone without having their symptoms recur, requiring an increase in the prednisone dose. A full battery of tests is done at the initial screening visit and at the 26- and 52-week follow-up visits, requiring hospitalization for 3-5 days. Additional interim outpatient assessments are done at 6, 12, 18 and 36 weeks. The full battery of tests at the initial screening and the 26- and 52-week visits includes the following:

• Medical history, physical examination, blood and urine tests, assessment of disease severity and activity.
• Questionnaires.
• Chest x-ray (CXR) and computed tomography (CT) scan.
• Abdominal ultrasound.
• Six-minute walk test (6MWT)
• Exercise testing and blood gases
• Pulmonary function tests (PFT)
• Maximum incremental ventilatory performance test (MIVP)
• Exhaled nitric oxide and carbon monoxide (Exhaled NO and CO)
• Bronchoscopy and lavage Interim testing at 6, 12, 18 and 36 weeks includes PFT, MIVP, Exhaled NO and CO, CXR, questionnaire, blood tests, and 6MWT. Six months after completing the study, participants fill out a questionnaire.

Conditions

Sarcoidosis, Pulmonary

Keywords

Granulomatous Inflammation; Steroid-Sparing; Pulmonary Function; Sarcoidosis, Pulmonary; Statins (Atorvastatin); Biomarkers; Nitric Oxide; Disease Activity; Quality of Life; Corticosteroids; Pulmonary Sarcoidosis; Sarcoidosis

Outcome Measures

Primary Outcomes (1)

• The Steroid Sparing Period

  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.

  1 year

Secondary Outcomes (4)

• Pulmonary Sarcoidosis Flares

  1 year

• Pulmonary Function Tests

  12 month treatment period

• Exercise Performance

  12 month treatment period

• Quality of Life and Dyspnea Scales

  12 month treatment period

Other Outcomes (1)

• Chest Imaging

  12 month treatment period

Study Arms (2)

Intervention Arm (Atorvastatin)

ACTIVE COMPARATOR

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.

Drug: Atorvastatin

Control Arm (Placebo)

PLACEBO COMPARATOR

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

Other: Placebo Oral Tablet

Interventions

Atorvastatin DRUG

Placebo vs. Atorvastatin

Also known as: Lipitor

Intervention Arm (Atorvastatin)

Placebo Oral Tablet OTHER

Placebo: Sham Therapy in an oral tablet formulation

Also known as: Placebo

Control Arm (Placebo)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients are eligible for the trial if they are 18-70 years old with radiographic stages II and III pulmonary sarcoidosis, and are on prednisone, methotrexate, or azathioprine for pulmonary sarcoidosis or who are steroid-requiring. Patients with extra-pulmonary sarcoidosis (except cardiac and neurosarcoidosis) may be eligible as long as they have active pulmonary (stage II or III) sarcoidosis.
• Steroid-Requiring History:
• A steroid-requiring patient is one who was previously stable but who ultimately experiences (a) increased symptoms associated with radiographic deterioration, and/or, (b) met the criteria for relapse and/or functional deterioration. In addition, patients who were prescribed prednisone for sarcoidosis, but have self-discontinued it (yet still have clinical and symptomatic disease and/or evidence of pulmonary functional deterioration) will be considered steroid-requiring.
• This latter group of steroid-requiring patients is eligible for enrollment if they are willing to resume taking their latest stabilizing dose of prednisone for at least four weeks prior to study entry. If their dose cannot be determined, then 40 mg will be used.
• Therefore, a history of symptomatic or clinical deterioration leading to therapy initiation, or a history of decline associated with attempts to decrease therapy should be established. Medical records review and discussion with the prescribing physician will be used to establish this history.
• Radiographic Stages of Pulmonary Sarcoidosis:
• STAGE\< TAB\> DESCRIPTION
• \< TAB\> Normal Chest Radiograph
• I\< TAB\> Bilateral Hilar Lymphadenopathy
• II\< TAB\> Pulmonary Infiltration and Bilateral Hilar Lymphadenopathy
• III\< TAB\> Pulmonary Infiltration alone
• Steroid-requiring refers to one of three situations:
• Patients who meet relapse criteria or functional deterioration.
• Functional deterioration criteria that warrants prednisone therapy includes:
• If VC fell to 75% of the best recorded value for the patient before any treatment

You may not qualify if:

• Moderate to severe pulmonary fibrosis (stage IV sarcoidosis greater than 50% fibrosis)
• Lung Disease such as asthma, COPD, ILD (other than sarcoid-related)
• History of significant beryllium or asbestos exposure
• Pregnancy; or Active lactation/ child-bearing age female without appropriate birth control methods
• HIV disease
• Hepatitis C and Active Hepatitis B
• Other intervention protocols
• Immunosuppressive therapy (systemic or inhaled) other than corticosteroids or methotrexate
• Significant cardiac disease (NYSHA class greater than III), or serious coronary disease (unstable angina)
• Use of statins within 12 weeks of enrollment
• Allergies or intolerance to statins
• Liver disease (transaminases greater than 1.5X upper limits of normal) or cirrhosis
• Bleeding diathesis that is not correctable
• Inability to perform CPET (cycle ergometer) or PFT maneuvers
• Inability to understand the risks of the trial and the inability to complete the questionnaire

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Statement on sarcoidosis. Joint Statement of the American Thoracic Society (ATS), the European Respiratory Society (ERS) and the World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) adopted by the ATS Board of Directors and by the ERS Executive Committee, February 1999. Am J Respir Crit Care Med. 1999 Aug;160(2):736-55. doi: 10.1164/ajrccm.160.2.ats4-99. No abstract available.

  PMID: 10430755 BACKGROUND

• Newman LS, Rose CS, Maier LA. Sarcoidosis. N Engl J Med. 1997 Apr 24;336(17):1224-34. doi: 10.1056/NEJM199704243361706. No abstract available.

  PMID: 9110911 BACKGROUND

• Thomas KW, Hunninghake GW. Sarcoidosis. JAMA. 2003 Jun 25;289(24):3300-3. doi: 10.1001/jama.289.24.3300. No abstract available.

  PMID: 12824213 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Sarcoidosis, Pulmonary; Sarcoidosis

Interventions

Atorvastatin

Condition Hierarchy (Ancestors)

Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Hypersensitivity, Delayed; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids

Limitations and Caveats

The recruitment goal of 96 subjects was not met due to slow accrual. The primary endpoint analysis was based on the available subject data.

Results Point of Contact

• Title: Joseph Fontana, MD
• Organization: The National Institutes of Health/ The National Heart, Lung, and Blood Institute

fontanaj@nhlbi.nih.gov

301-451-7740

Study Officials

• Joseph R Fontana, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff Clinician

Study Record Dates

• First Submitted: January 18, 2006
• First Posted: January 19, 2006
• Study Start: January 1, 2006
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: May 22, 2017
• Results First Posted: August 12, 2016

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)