Use of Roflumilast to Prevent Exacerbations in Fibrotic Sarcoidosis Patients (REFS)

Study Overview
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Brief Summary
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Pulmonary sarcoidosis patients with fibrosis often develop recurrent episodes of bronchitis. These can lead to worsening of disease for both the short and long term. Roflumilast has been shown to reduce the number of acute bronchitis episodes in patients with COPD. Drugs similar to Roflumilast have been shown to help sarcoidosis. The current study is to determine if Roflumilast will reduce number of episodes of bronchitis and help fibrotic sarcoidosis.

Detailed Description
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This will be a multicenter, double blind, placebo controlled study. Patients would be randomized 1:1 to receive either roflumilast 500 mcg per day or placebo added to their current treatment regimen for twelve months.

Official Title
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Use of Roflumilast to Prevent Exacerbations in Fibrotic Sarcoidosis Patients (REFS)

Conditions
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Sarcoidosis

Intervention / Treatment
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* Drug: Roflumilast
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with sarcoidosis as defined by the American Thoracic Society criteria Patients with an FEV1/FVC ratio of less than 80% Patients with fibrosis on chest x-ray and/or high resolution CT scan. Patients have had at least two exacerbations of their sarcoidosis in the prior year. An exacerbation is defined as an acute event requiring increase of prednisone with or without use of antibiotics. Patients must be on a stable dose of corticosteroids and other agents for their sarcoidosis at least 4 weeks prior to first visit. For patients on prednisone alone, the dose has to be the equivalent of 5 mg prednisone a day. For those on other immunosuppressants, they can be on any dose of prednisone. Patients must be between ages of 18 and 70 years of age. Willing to take prednisone at increased dosage for exacerbations of their sarcoidosis. Patients must be able to provide written informed consent to participate in the study. Exclusion Criteria: Patients with known hypersensitivity to theophylline or pentoxifylline will not be eligible. Patients with dose dependent nausea from these drugs may still participate in the trial. Patients will not be able to take theophylline or pentoxifylline during the time of the study. They will be allowed to take drugs for sarcoidosis including prednisone, methotrexate, azathioprine, leflunomide, hydroxychloroquine, thalidomide, infliximab, adalimumab, and rituximab. Patients with serum creatinine of greater than 3 mg/dL Patients with moderate or severe liver disease as defined Child Pugh class 3 or 4. Patients with unstable cardiac disease Patients with non cutaneous malignancy treated in the past two years. Patients unable to complete the questionnaires and six minute walks detailed in the study.Women of child bearing potential unable to use adequate birth control as determined by the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Roflumilast<br>Roflumilast | Drug: Roflumilast<br>* Roflumilast<br>* Other names: Daliresp;|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Placebo one a day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in number of episodes of acute exacerbation | Collect number of episodes of exacerbtion in one year | one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in FVC | Changes in FVC over time of the study | one year | 
| Changes in quality of life | Measure QOL using Sarcoidosis health question, fatigue assessment score, SGRQ, SF-36 Leicester cough questionnaire | One year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sarcoidosis, fibrosis, bronchiectasis