Phase II Investigation of Antimycobacterial Therapy on Progressive, Pulmonary Sarcoidosis

NCT ID: NCT02024555

Last Updated: 2020-07-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 97 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-31
• Study Completion Date: 2019-04-01

Brief Summary

The primary purpose of this study is to investigate the efficacy and safety of oral antimycobacterial therapy in patients with confirmed progressive pulmonary sarcoidosis. We suspect that the CLEAR regimen will improve the absolute FVC percent predicted in chronic pulmonary sarcoidosis participants.

Detailed Description

Primary Objective: To assess the efficacy and safety of oral CLEAR therapy in patients with confirmed progressive pulmonary sarcoidosis.

Hypothesis: The CLEAR regimen will improve the absolute FVC percent predicted in chronic pulmonary sarcoidosis participants by augmenting T cell responses through the normalization of p56Lck expression and IL-2 production.

Conditions

Sarcoidosis; Antimycobacterial Therapy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Concomitant Levaquin, Ethambutol, Azithromycin and Rifampin

Levofloxacin 500mg po QD; Ethambutol 1200mg po QD; Azithromycin 250 mg po QD; Rifampin 600mg po QD or Rifabutin 300mg po QD

Group Type: ACTIVE_COMPARATOR

Levofloxacin

Intervention Type: DRUG

Ethambutol

Intervention Type: DRUG

Azithromycin

Intervention Type: DRUG

Rifampin

Intervention Type: DRUG

Placebo

Riboflavin will be used for rifampin; encapsulated microcrystalline cellulose will be used to replace the levofloxacin, ethambutol and azithromycin.

The pill count will be the same as the comparator regimen.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

This will serve as a placebo to the antibiotics used in antimycobacterial therapy.

Interventions

Levofloxacin

Intervention Type: DRUG

Ethambutol

Intervention Type: DRUG

Azithromycin

Intervention Type: DRUG

Rifampin

Intervention Type: DRUG

Placebo

This will serve as a placebo to the antibiotics used in antimycobacterial therapy.

Intervention Type: DRUG

Other Intervention Names

Levaquin; Z-pack; Rifadin, Rimactane

Eligibility Criteria

Inclusion Criteria

1. Patients with sarcoidosis as defined by the ATS/ERS/WASOG statement on sarcoidosis as defined by the clinical presentation consistent with sarcoidosis, as well as biopsy demonstrating granulomas, and no alternative for the cause of the granulomas, such as tuberculosis for at least one year prior to randomization.

2. Evidence of disease progression as defined by at least one of the following three criteria:

Decline of absolute percent predicted of FVC (FVC ≥45% or higher of predicted value) or DLCO of at least 5% on serial measurements (DLCO range >35%, if measured); Radiographic progression in chest imaging on side by side comparison; Change in dyspnea score, as measured by Transition Dyspnea Index (TDI); Positive peripheral immune responses to ESAT-6 as a biomarker of response to CLEAR regimen.

3. Possess evidence of parenchymal or nodal disease on chest radiograph.

Exclusion Criteria

1. Inability to obtain consent

2. Age less than 18 years

3. Female participants of childbearing potential not willing to use one of the following methods of birth control for the duration of the study and 90 days after study completion: condoms, sponge, foams, jellies, diaphragm, non-hormonal intrauterine device, a vasectomized sole partner or abstinence. Note: Oral contraceptive pills are not effective birth control when taking rifamycin. A negative urine pregnancy test at screening visit if female of childbearing potential

4. FVC predicted value is < 45%.

5. End-stage fibrotic pulmonary disease.

6. Significant underlying liver disease.

7. Allergy or intolerance to any of the antibiotics within the CLEAR regimen.

8. Allergy or intolerance to albuterol

9. Poor venous access for obtaining blood samples

10. History of active tuberculosis, close contact with a person with active tuberculosis within the 6 months prior to the screening visit or has a positive PPD.

11. Significant disorder, other than sarcoidosis, that would complicate the treatment evaluation, (such as respiratory, cardiac, neurologic, musculoskeletal or seizure disorders)

12. Use of an investigational drug within 30 days prior to screening or within 5 half-lives of the agent, whichever is longer.

13. Currently receiving >40mg prednisone.

14. ALT or AST >5 times upper limit of normal (ULN)

15. Leukopenia, as defined by WBC <3.0 cells/mm3 or absolute neutrophil count <1000

16. Breast feeding.

17. Color perception impairment as defined by the inability to differentiate colors per personal history or history of optic neuritis from any cause, including from sarcoidosis.

18. If patient is on immunomodulators, they must be on regimen for ≥ 3-month period and on a stable dose for > 4 weeks.

19. Family or personal history of long QT interval

20. Most recent nuclear medicine scan or echocardiogram (if done), demonstrating cardiac ejection fraction <35%

21. Participant has persistent or active infection(s) requiring hospitalization or treatment with antibiotics, antiretrovirals, or antifungals within 30 days prior to baseline. Minocycline and doxycycline are not considered antibiotics when used to treat sarcoidosis.

22. Any significant finding in the patient's medical history or physical or psychiatric exam prior to or after randomization that, in the opinion of the investigator, would affect patient safety or compliance or ability to deliver the study drug according to protocol.

23. On medications that interact with the antibiotics of the CLEAR regimen

24. History of or receiving treatment for pulmonary hypertension. Receiving biologic medication within the 6 months prior to screening visit

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Vanderbilt University

OTHER

Sponsor Role: lead

Responsible Party

Wonder Drake

Associate Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Wonder Drake, MD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University School of Medicine

Locations

Albany Medical Center

Albany, New York, United States

University of Cincinnati

Cincinnati, Ohio, United States

Cleveland Clinic

Cleveland, Ohio, United States

Ohio State University

Columbus, Ohio, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Vanderbilt University School of Medicine

Nashville, Tennessee, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

R01HL117074-01

Identifier Type: NIH

Identifier Source: secondary_id

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R01HL117074

Identifier Type: NIH

Identifier Source: org_study_id

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