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

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.

Study Overview

• Status: Unknown
• Conditions: Sarcoidosis
• Intervention / Treatment: Drug: Roflumilast; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with sarcoidosis as defined by the American Thoracic Society criteria
2. Patients with an FEV1/FVC ratio of less than 80%
3. Patients with fibrosis on chest x-ray and/or high resolution CT scan.
4. 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.
5. Patients must be on a stable dose of corticosteroids and other agents for their sarcoidosis at least 4 weeks prior to first visit.
6. 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.
7. Patients must be between ages of 18 and 70 years of age.
8. Willing to take prednisone at increased dosage for exacerbations of their sarcoidosis.
9. Patients must be able to provide written informed consent to participate in the study.

Exclusion Criteria:

1. 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.
2. 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.
3. Patients with serum creatinine of greater than 3 mg/dL
4. Patients with moderate or severe liver disease as defined Child Pugh class 3 or 4.
5. Patients with unstable cardiac disease
6. Patients with non cutaneous malignancy treated in the past two years.
7. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo; Placebo one a day
EXPERIMENTAL: Roflumilast	Drug: Roflumilast; Roflumilast; Other Names: Daliresp

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety	recard adverse events	one year

Collaborators and Investigators

• Sponsor: University of Cincinnati
• Collaborators: University of Pittsburgh; The Cleveland Clinic; University of Illinois at Chicago; Henry Ford Health System; Albany Medical College

Publications and helpful links

General Publications

• Baughman RP, Judson MA, Culver DA, Birring SS, Parambil J, Zeigler J, Lower EE. Roflumilast (Daliresp(R)) to reduce acute pulmonary events in fibrotic sarcoidosis: a multi-center, double blind, placebo controlled, randomized clinical trial. Sarcoidosis Vasc Diffuse Lung Dis. 2021;38(3):e2021035. doi: 10.36141/svdld.v38i3.11684. Epub 2021 Sep 30.

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (ANTICIPATED): May 1, 2016
• Study Completion (ANTICIPATED): October 1, 2016

Study Registration Dates

• First Submitted: April 10, 2013
• First Submitted That Met QC Criteria: April 10, 2013
• First Posted (ESTIMATE): April 12, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): December 8, 2015
• Last Update Submitted That Met QC Criteria: December 4, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: Sarcoidosis, fibrosis, bronchiectasis
• Additional Relevant MeSH Terms: Lymphoproliferative Disorders; Lymphatic Diseases; Sarcoidosis
• Other Study ID Numbers: REFS-1; WIRB Pr #: 20130426 (OTHER: WIRB)