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Phase 2 N=97 Randomized Quadruple-blind Treatment

Phase II Investigation of Antimycobacterial Therapy on Progressive, Pulmonary Sarcoidosis

Sarcoidosis; Antimycobacterial Therapy

Enrolled (actual)
97
Serious AEs
7.2%
Results posted
Jul 2020
Primary outcome: Primary: 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. — 0.35; 0.17 percentage predicted absolute FVC

Study Design & Population

Study type
Interventional
Phase
Phase 2
Interventions
Levofloxacin (Drug); Ethambutol (Drug); Azithromycin (Drug); Rifampin (Drug); Placebo (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
Vanderbilt University
Primary completion
Apr 2019

Outcome Measures

OutcomeResultp-value
PRIMARY
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.
0.35; 0.17
SECONDARY
Radiographic Improvement in Sarcoidosis Lung Disease by Frontal Chest X-ray .
SECONDARY
Six Minute Walk, Distance in Meters
416.25; 416.41; 432.65; 428.35; 451.59; 420.21
SECONDARY
Change in Oxygen Saturation
0.39; -0.85; -0.12; -0.43; 2.54; -0.46
SECONDARY
Change in Level of Dyspnea
SECONDARY
Change in the Saint George's Respiratory Questionnaire (SGRQ)
-2.23; -6.30
SECONDARY
Fatigue Assessment Scale (FAS).
SECONDARY
Change in the King's Sarcoidosis Questionnaire (KSQ) for the Assessment of Health Status;
SECONDARY
Adverse Events
4; 3; 24; 16
SECONDARY
FEV1%
69.11; 67.45; 69.97; 73.81; 71.57; 69.56
SECONDARY
Failure of Standard Therapy
3; 2
SECONDARY
Abnormal Lab Values
1; 0; 5; 0; 3; 2

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.

Eligibility Criteria

Inclusion Criteria

  • 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.
  • 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.

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

Exclusion Criteria

  • Inability to obtain consent
  • Age less than 18 years
  • 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
  • FVC predicted value is 40mg prednisone.
  • ALT or AST >5 times upper limit of normal (ULN)
  • Leukopenia, as defined by WBC 4 weeks.
  • Family or personal history of long QT interval
  • Most recent nuclear medicine scan or echocardiogram (if done), demonstrating cardiac ejection fraction <35%
  • 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.
  • 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.
  • On medications that interact with the antibiotics of the CLEAR regimen
  • History of or receiving treatment for pulmonary hypertension. Receiving biologic medication within the 6 months prior to screening visit
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02024555). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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