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

• ClinicalTrials.gov Identifier: NCT01830959
• Recruitment Status: Unknown
• First Posted: April 12, 2013
• Last Update Posted: December 8, 2015
• Sponsor: University of Cincinnati
• Collaborators: The Cleveland Clinic; University of Pittsburgh; University of Illinois at Chicago; Henry Ford Health System; Albany Medical College
• Information provided by (Responsible Party): Robert P Baughman, University of Cincinnati

Tracking Information

• First Submitted Date: April 10, 2013
• First Posted Date: April 12, 2013
• Last Update Posted Date: December 8, 2015
• Study Start Date: April 2013
• Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 10, 2013)

Reduction in number of episodes of acute exacerbation [ Time Frame: one year ]

Collect number of episodes of exacerbtion in one year

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 10, 2013)

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

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: April 10, 2013)

Safety [ Time Frame: one year ]

recard adverse events

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

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

Brief Summary

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: 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
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Sarcoidosis

Intervention

• Drug: Roflumilast
  Roflumilast
  Other Name: Daliresp
• Drug: Placebo
  Placebo one a day

Study Arms

• Experimental: Roflumilast
  Roflumilast
  Intervention: Drug: Roflumilast
• Placebo Comparator: Placebo
  Placebo
  Intervention: Drug: Placebo

• 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.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: December 4, 2015): 50
• Original Estimated Enrollment (submitted: April 10, 2013): 60
• Estimated Study Completion Date: October 2016
• Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01830959
• Other Study ID Numbers: REFS-1; WIRB Pr #: 20130426 ( Other Identifier: WIRB )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Robert P Baughman, University of Cincinnati
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Cincinnati
• Original Study Sponsor: Same as current

Collaborators

• The Cleveland Clinic
• University of Pittsburgh
• University of Illinois at Chicago
• Henry Ford Health System
• Albany Medical College

Investigators

• Study Chair: Robert P Baughman, MD; University of Cincinnati

• PRS Account: University of Cincinnati
• Verification Date: December 2015