Phase II Investigation of Antimycobacterial Therapy on Progressive, Pulmonary Sarcoidosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02024555
Recruitment Status : Recruiting
First Posted : December 31, 2013
Last Update Posted : March 27, 2018
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Wonder Drake, Vanderbilt University

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.

Condition or disease Intervention/treatment Phase
Sarcoidosis; Antimycobacterial Therapy Drug: Levofloxacin Drug: Ethambutol Drug: Azithromycin Drug: Rifampin Drug: Placebo Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 128 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Investigation of the Efficacy of Antimycobacterial Therapy on Pulmonary Sarcoidosis Phase II Randomized, Double-blind, Placebo-controlled Trial
Study Start Date : March 2014
Estimated Primary Completion Date : March 2019
Estimated Study Completion Date : May 2019

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: 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
Drug: Levofloxacin
Other Name: Levaquin

Drug: Ethambutol
Drug: Azithromycin
Other Name: Z-pack

Drug: Rifampin
Other Name: Rifadin, Rimactane

Placebo Comparator: 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.

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

Primary Outcome Measures :
  1. Determine the effect of CLEAR therapy versus placebo on the change in percent predicted absolute forced vital capacity (FVC) in participants with pulmonary sarcoidosis, comparing baseline with performance after completion of 16 weeks of therapy. [ Time Frame: Baseline, 4, 8, 16 and 24 weeks ]

Secondary Outcome Measures :
  1. Radiographic improvement in sarcoidosis lung disease by frontal chest x-ray . [ Time Frame: Baseline and 16 weeks ]
  2. Change in 6 minute walk distance, oxygen saturation and level of dyspnea [ Time Frame: Baseline, 4, 8 and 16 weeks ]
    Outcome measure if a composite

  3. Change in the Saint George's Respiratory Questionnaire (SGRQ; King's Sarcoidosis Questionnaire (KSQ) for the assessment of health status; The Fatigue Assessment Scale (FAS). [ Time Frame: Baseline, 4, 8, 16 and 24 weeks ]
    Outcome measure if a composite

  4. Safety profile of regimen as evidenced by adverse events and abnormal lab values, tolerability and toxicity of the treatment regimen including comparison of reported adverse events and abnormal laboratory values compared to placebo. [ Time Frame: Baseline, 4, 8, 16 and 24 weeks ]
  5. Change in FEV1 [ Time Frame: Baseline, 4, 8, 16 and 24 weeks ]
  6. Failure of standard Therapy [ Time Frame: Baseline, 4, 8, and 16 weeks ]
    We will assess how many subjects in either arm need escalation of their standard regimen (ie increase in prednisone) during the 16 weeks.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02024555

Contact: Wonder Drake, MD 615-322-2035

United States, New York
Albany Medical Center Recruiting
Albany, New York, United States, 12208
Contact: Marc Judson, MD    518-262-5196   
Contact: Leahruth Saavedra, MS    (518) 262-0355   
Sub-Investigator: Marc Judson, MD         
United States, Ohio
University of Cincinnati Recruiting
Cincinnati, Ohio, United States, 45267
Contact: Robert Baughman, MD    513-584-5110   
Contact: Joyce Zeigler    (513) 584-6252   
Principal Investigator: Robert Baughman, MD         
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
Contact: Dan Culver, DO    216-444-6508   
Contact: Allison Wimer    216-444-9975   
Principal Investigator: Dan Culver, DO         
Ohio State University Recruiting
Columbus, Ohio, United States, 43221
Contact: Elliott Crouser, M.D.    614-293-4925   
Contact: Karen Martin    614-293-4978   
Sub-Investigator: Elliott Crouser, M.D.         
United States, South Carolina
Medical University of South Carolina Recruiting
Charleston, South Carolina, United States, 29425
Contact: Ennis James, MD    843-792-3769   
Contact: Robyn Do    (843) 792-1221   
Sub-Investigator: Ennis James, MD         
United States, Tennessee
Vanderbilt University School of Medicine Recruiting
Nashville, Tennessee, United States, 37232
Contact: Wonder Drake, MD    615-322-2035   
Contact: Amy Kerrigan, MSN    615-343-3238   
Principal Investigator: Wonder Drake, MD         
Sponsors and Collaborators
Vanderbilt University
National Heart, Lung, and Blood Institute (NHLBI)
Principal Investigator: Wonder Drake, MD Vanderbilt University School of Medicine

Responsible Party: Wonder Drake, Associate Professor of Medicine, Vanderbilt University Identifier: NCT02024555     History of Changes
Other Study ID Numbers: R01HL117074 ( U.S. NIH Grant/Contract )
R01HL117074-01 ( U.S. NIH Grant/Contract )
First Posted: December 31, 2013    Key Record Dates
Last Update Posted: March 27, 2018
Last Verified: March 2018

Additional relevant MeSH terms:
Sarcoidosis, Pulmonary
Lymphoproliferative Disorders
Lymphatic Diseases
Lung Diseases, Interstitial
Lung Diseases
Respiratory Tract Diseases
Anti-Bacterial Agents
Anti-Infective Agents, Urinary
Anti-Infective Agents
Renal Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Cytochrome P-450 CYP1A2 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Antibiotics, Antitubercular
Antitubercular Agents
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP2C8 Inducers
Cytochrome P-450 CYP2C19 Inducers