Atorvastatin to Treat Pulmonary Sarcoidosis

• INCLUSION CRITERIA:

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 DESCRIPTION

0 Normal Chest Radiograph

I Bilateral Hilar Lymphadenopathy

II Pulmonary Infiltration and Bilateral Hilar Lymphadenopathy

III 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

If VC fell to greater than 50% of predicted value

IF DLCO fell to less than 60% of the best recorded value prior to their treatment

Patients who are on a previously prescribed systemic steroid, or alternative agent such as methotrexate or azathioprine, primarily for pulmonary sarcoidosis. Alternative agents must first be changed to roughly equivalent anti-inflammatory dose of prednisone and the patient should be stable on this dose for at least four weeks prior to randomization.

Patients who have substantial respiratory symptoms (distressing cough or dyspnea, which interferes with daily activities that would warrant therapy as per the standard of practice in the US.

Extra Pulmonary Sarcoidosis:

Patients with extra pulmonary sarcoidosis (except neurosarcoidosis and cardiac sarcoidosis) may be eligible as long as they have active pulmonary (stage II or III) sarcoidosis. All patients will be referred to an NIH ophthalmologist. Steroid therapy may be modified based upon the recommendations of the consultants, as well as per the lapse criteria described above.

EXCLUSION CRITERIA

• 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 risk