Phase II Investigation of Antimycobacterial Therapy on Progressive, Pulmonary Sarcoidosis

• Sponsor: Vanderbilt University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02024555
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Enrollment: 97
• Locations: 6
• Arms: 2
• Duration (Months): 61
• Patients Per Site: 16.2
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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 Design

• Study Type: Interventional
• Actual Enrollment: 97 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: Mar 1, 2014
• Actual Primary Completion Date: Apr 1, 2019
• Actual Study Completion Date: Apr 1, 2019

Arms and Interventions

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 Names: Levaquin ; Drug: Ethambutol; Drug: Azithromycin; Other Names: Z-pack ; Drug: Rifampin; Other Names: 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.

Outcome Measures

Primary Outcome Measures

1. 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. [Baseline to 16 weeks]

   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. This will involve comparing sarcoidosis and placebo after 16 weeks of therapy.

Secondary Outcome Measures

1. Radiographic Improvement in Sarcoidosis Lung Disease by Frontal Chest X-ray . [Baseline and 16 weeks]

   Radiographic improvement in sarcoidosis lung disease by frontal chest x-ray . Local investigators will score chest x-rays.

2. Six Minute Walk, Distance in Meters [Baseline, 4, 8, and 16 and 24 weeks]

   The 6-min walk test (6 MWT) is a submaximal exercise test that entails measurement of distance walked over a span of 6 minutes.

3. Change in Oxygen Saturation [Baseline, 4, 8, and 16 and 24 weeks]

   measured using pulse oximetry

4. Change in Level of Dyspnea [Baseline, 4, 8 and 16 weeks]

   Outcome measure if a composite

5. Change in the Saint George's Respiratory Questionnaire (SGRQ) [Baseline and 16 weeks]

   The SGRQ is a 50-item questionnaire developed to measure health status (quality of life) in patients with diseases of airways obstruction. Scores range from 0 to 100, with higher scores indicating more limitations. A minimum change in score of 4 units was established as clinically relevant after patient and clinician testing.

6. Fatigue Assessment Scale (FAS). [Baseline, 4, 8, 16 and 24 weeks]

   The FAS is a 10-item general fatigue questionnaire to assess fatigue. Total scores can range from 10, indicating the lowest level of fatigue, to 50, denoting the highest.

7. Change in the King's Sarcoidosis Questionnaire (KSQ) for the Assessment of Health Status; [Baseline and 16 weeks]

   The KSQ is a free, online questionnaire to be filled out by sarcoidosis patients. The questionnaire takes around 10 minutes and is split into 5 sections; general health status, lungs, medication, skin and eyes. There are 29 questions in total, however some questions may not be answered (depending on the type of sarcoidosis affected). Each question asks patients to rate how they feel about many different aspects of their life, for instance how much pain they are in or how difficult they find everyday tasks. Information provided is confidential. Results are given as a number between 1-100 with higher numbers indicating better health.

8. Adverse Events [24 weeks]

   Safety profile of regimen as evidenced by the number of adverse events

9. FEV1% [Baseline, 4, 8, and 16 and 24 weeks]

   FEV1% was measure pre and post 6 minute walk test

10. Failure of Standard Therapy [Baseline to 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.

11. Abnormal Lab Values [baseline to 16 weeks]

    Safety profile of regimen as evidenced by the number of abnormal lab values classified as Adverse Events

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• 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.

1. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Albany Medical Center	Albany	New York	United States	12208
2	University of Cincinnati	Cincinnati	Ohio	United States	45267
3	Cleveland Clinic	Cleveland	Ohio	United States	44195
4	Ohio State University	Columbus	Ohio	United States	43221
5	Medical University of South Carolina	Charleston	South Carolina	United States	29425
6	Vanderbilt University School of Medicine	Nashville	Tennessee	United States	37232

Sponsors and Collaborators

• Vanderbilt University
• National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Wonder Drake, MD, Vanderbilt University School of Medicine

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 5, 2018

More Information

Publications

None provided.

• Responsible Party: Wonder Drake, Associate Professor of Medicine, Vanderbilt University
• ClinicalTrials.gov Identifier: NCT02024555
• Other Study ID Numbers: R01HL117074; R01HL117074-01
• First Posted: Dec 31, 2013
• Last Update Posted: Jul 9, 2020
• Last Verified: Jun 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Sarcoidosis, Pulmonary; Sarcoidosis; Azithromycin; Levofloxacin; Ofloxacin; Rifampin; Ethambutol

Study Results

Participant Flow

Pre-assignment Detail	446 participants were screened but only 97 participants met inclusion/exclusion and were randomized.

Arm/Group Title	Concomitant Levaquin, Ethambutol, Azithromycin and Rifampin	Placebo
Arm/Group Description	Levofloxacin 500mg po QD; Ethambutol 1200mg po QD; Azithromycin 250 mg po QD; Rifampin 600mg po QD or Rifabutin 300mg po QD Levofloxacin Ethambutol Azithromycin Rifampin	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. Placebo: This will serve as a placebo to the antibiotics used in antimycobacterial therapy.
Period Title: Overall Study
STARTED	49	48
COMPLETED	43	46
NOT COMPLETED	6	2

Baseline Characteristics

Arm/Group Title	Concomitant Levaquin, Ethambutol, Azithromycin and Rifampin	Placebo	Total
Arm/Group Description	Levofloxacin 500mg po QD; Ethambutol 1200mg po QD; Azithromycin 250 mg po QD; Rifampin 600mg po QD or Rifabutin 300mg po QD Levofloxacin Ethambutol Azithromycin Rifampin	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. Placebo: This will serve as a placebo to the antibiotics used in antimycobacterial therapy.	Total of all reporting groups
Overall Participants	49	48	97
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.5 (9.8)	54.5 (10.4)	54.5 (10)
Sex: Female, Male (Count of Participants)
Female	20 40.8%	27 56.3%	47 48.5%
Male	29 59.2%	21 43.8%	50 51.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 2%	2 4.2%	3 3.1%
Not Hispanic or Latino	48 98%	46 95.8%	94 96.9%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	1 2.1%	1 1%
Black or African American	15 30.6%	13 27.1%	28 28.9%
White	34 69.4%	34 70.8%	68 70.1%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	49 100%	48 100%	97 100%
Weight (kilograms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms]	92.78 (24.45)	97.54 (21.99)	95.19 (23.24)
Heart Rate (beats per minute) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [beats per minute]	79.59 (17.7)	76.19 (11.66)	77.91 (13.33)
6 minute walk test (meters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [meters]	416.25 (140.69)	416.49 (105.16)	416.33 (123.55)

Outcome Measures

1. Primary Outcome

Title	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.
Description	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. This will involve comparing sarcoidosis and placebo after 16 weeks of therapy.
Time Frame	Baseline to 16 weeks

Outcome Measure Data

Analysis Population Description

Only 43 participants in each arm completed this measure

Arm/Group Title	Concomitant Levaquin, Ethambutol, Azithromycin and Rifampin	Placebo
Arm/Group Description	Levofloxacin 500mg po QD; Ethambutol 1200mg po QD; Azithromycin 250 mg po QD; Rifampin 600mg po QD or Rifabutin 300mg po QD Levofloxacin Ethambutol Azithromycin Rifampin	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. Placebo: This will serve as a placebo to the antibiotics used in antimycobacterial therapy.
Measure Participants	43	43
Mean (Standard Deviation) [percentage predicted absolute FVC]	0.35 (6.76)	0.17 (7.2)

2. Secondary Outcome

Title	Radiographic Improvement in Sarcoidosis Lung Disease by Frontal Chest X-ray .
Description	Radiographic improvement in sarcoidosis lung disease by frontal chest x-ray . Local investigators will score chest x-rays.
Time Frame	Baseline and 16 weeks

Outcome Measure Data

Analysis Population Description

The outcome was not completed due to lack of funds for radiology services.

Arm/Group Title	Concomitant Levaquin, Ethambutol, Azithromycin and Rifampin	Placebo
Arm/Group Description	Levofloxacin 500mg po QD; Ethambutol 1200mg po QD; Azithromycin 250 mg po QD; Rifampin 600mg po QD or Rifabutin 300mg po QD Levofloxacin Ethambutol Azithromycin Rifampin	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. Placebo: This will serve as a placebo to the antibiotics used in antimycobacterial therapy.
Measure Participants	0	0

3. Secondary Outcome

Title	Six Minute Walk, Distance in Meters
Description	The 6-min walk test (6 MWT) is a submaximal exercise test that entails measurement of distance walked over a span of 6 minutes.
Time Frame	Baseline, 4, 8, and 16 and 24 weeks

Outcome Measure Data

Analysis Population Description

Week 24 assessment was optional. Not all participants completed the 6 minute walk test.

Arm/Group Title	Concomitant Levaquin, Ethambutol, Azithromycin and Rifampin	Placebo
Arm/Group Description	Levofloxacin 500mg po QD; Ethambutol 1200mg po QD; Azithromycin 250 mg po QD; Rifampin 600mg po QD or Rifabutin 300mg po QD Levofloxacin Ethambutol Azithromycin Rifampin	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. Placebo: This will serve as a placebo to the antibiotics used in antimycobacterial therapy.
Measure Participants	48	48
Baseline	416.25 (140.69)	416.41 (105.15)
Week 4	432.65 (155.5)	428.35 (92.36)
Week 8	451.59 (146.12)	420.21 (93.9)
Week 16	440.37 (137.08)	430.85 (111.96)
Week 24	444.68 (165.09)	425.18 (104.95)

4. Secondary Outcome

Title	Change in Oxygen Saturation
Description	measured using pulse oximetry
Time Frame	Baseline, 4, 8, and 16 and 24 weeks

Outcome Measure Data

Analysis Population Description

not all participants completed the measure and it was not recorded at week 24

Arm/Group Title	Concomitant Levaquin, Ethambutol, Azithromycin and Rifampin	Placebo
Arm/Group Description	Levofloxacin 500mg po QD; Ethambutol 1200mg po QD; Azithromycin 250 mg po QD; Rifampin 600mg po QD or Rifabutin 300mg po QD Levofloxacin Ethambutol Azithromycin Rifampin	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. Placebo: This will serve as a placebo to the antibiotics used in antimycobacterial therapy.
Measure Participants	49	48
Baseline to week 4	0.39 (3.33)	-0.85 (1.95)
Baseline to week 8	-0.12 (2.95)	-0.43 (3.31)
Baseline to week 16	2.54 (14.80)	-0.46 (3.79)

5. Secondary Outcome

Title	Change in Level of Dyspnea
Description	Outcome measure if a composite
Time Frame	Baseline, 4, 8 and 16 weeks

Outcome Measure Data

Analysis Population Description

this measure was not administered

Arm/Group Title	Concomitant Levaquin, Ethambutol, Azithromycin and Rifampin	Placebo
Arm/Group Description	Levofloxacin 500mg po QD; Ethambutol 1200mg po QD; Azithromycin 250 mg po QD; Rifampin 600mg po QD or Rifabutin 300mg po QD Levofloxacin Ethambutol Azithromycin Rifampin	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. Placebo: This will serve as a placebo to the antibiotics used in antimycobacterial therapy.
Measure Participants	0	0

6. Secondary Outcome

Title	Change in the Saint George's Respiratory Questionnaire (SGRQ)
Description	The SGRQ is a 50-item questionnaire developed to measure health status (quality of life) in patients with diseases of airways obstruction. Scores range from 0 to 100, with higher scores indicating more limitations. A minimum change in score of 4 units was established as clinically relevant after patient and clinician testing.
Time Frame	Baseline and 16 weeks

Outcome Measure Data

Analysis Population Description

questionnaire was only administered at baseline and 16 weeks and not all participants completed the questionnaire at week 16

Arm/Group Title	Concomitant Levaquin, Ethambutol, Azithromycin and Rifampin	Placebo
Arm/Group Description	Levofloxacin 500mg po QD; Ethambutol 1200mg po QD; Azithromycin 250 mg po QD; Rifampin 600mg po QD or Rifabutin 300mg po QD Levofloxacin Ethambutol Azithromycin Rifampin	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. Placebo: This will serve as a placebo to the antibiotics used in antimycobacterial therapy.
Measure Participants	41	39
Mean (Standard Error) [score on a scale]	-2.23 (11.9)	-6.30 (9)

7. Secondary Outcome

Title	Fatigue Assessment Scale (FAS).
Description	The FAS is a 10-item general fatigue questionnaire to assess fatigue. Total scores can range from 10, indicating the lowest level of fatigue, to 50, denoting the highest.
Time Frame	Baseline, 4, 8, 16 and 24 weeks

Outcome Measure Data

Analysis Population Description

The FAS was not administered to participants.

Arm/Group Title	Concomitant Levaquin, Ethambutol, Azithromycin and Rifampin	Placebo
Arm/Group Description	Levofloxacin 500mg po QD; Ethambutol 1200mg po QD; Azithromycin 250 mg po QD; Rifampin 600mg po QD or Rifabutin 300mg po QD Levofloxacin Ethambutol Azithromycin Rifampin	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. Placebo: This will serve as a placebo to the antibiotics used in antimycobacterial therapy.
Measure Participants	0	0

8. Secondary Outcome

Title	Change in the King's Sarcoidosis Questionnaire (KSQ) for the Assessment of Health Status;
Description	The KSQ is a free, online questionnaire to be filled out by sarcoidosis patients. The questionnaire takes around 10 minutes and is split into 5 sections; general health status, lungs, medication, skin and eyes. There are 29 questions in total, however some questions may not be answered (depending on the type of sarcoidosis affected). Each question asks patients to rate how they feel about many different aspects of their life, for instance how much pain they are in or how difficult they find everyday tasks. Information provided is confidential. Results are given as a number between 1-100 with higher numbers indicating better health.
Time Frame	Baseline and 16 weeks

Outcome Measure Data

Analysis Population Description

KSQ was not administered to participants.

Arm/Group Title	Concomitant Levaquin, Ethambutol, Azithromycin and Rifampin	Placebo
Arm/Group Description	Levofloxacin 500mg po QD; Ethambutol 1200mg po QD; Azithromycin 250 mg po QD; Rifampin 600mg po QD or Rifabutin 300mg po QD Levofloxacin Ethambutol Azithromycin Rifampin	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. Placebo: This will serve as a placebo to the antibiotics used in antimycobacterial therapy.
Measure Participants	0	0

9. Secondary Outcome

Title	Adverse Events
Description	Safety profile of regimen as evidenced by the number of adverse events
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Concomitant Levaquin, Ethambutol, Azithromycin and Rifampin	Placebo
Arm/Group Description	Levofloxacin 500mg po QD; Ethambutol 1200mg po QD; Azithromycin 250 mg po QD; Rifampin 600mg po QD or Rifabutin 300mg po QD Levofloxacin Ethambutol Azithromycin Rifampin	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. Placebo: This will serve as a placebo to the antibiotics used in antimycobacterial therapy.
Measure Participants	49	48
Serious Adverse Events	4	3
Non-Serious Adverse Events	24	16

10. Secondary Outcome

Title	FEV1%
Description	FEV1% was measure pre and post 6 minute walk test
Time Frame	Baseline, 4, 8, and 16 and 24 weeks

Outcome Measure Data

Analysis Population Description

Week 24 assessment was optional. Not all participants completed all measurements

Arm/Group Title	Concomitant Levaquin, Ethambutol, Azithromycin and Rifampin	Placebo
Arm/Group Description	Levofloxacin 500mg po QD; Ethambutol 1200mg po QD; Azithromycin 250 mg po QD; Rifampin 600mg po QD or Rifabutin 300mg po QD Levofloxacin Ethambutol Azithromycin Rifampin	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. Placebo: This will serve as a placebo to the antibiotics used in antimycobacterial therapy.
Measure Participants	49	48
Baseline pre	69.11 (17.23)	67.45 (17.85)
Baseline post	69.97 (17.01)	73.81 (18.91)
4 weeks pre	71.57 (17.31)	69.56 (20.52)
4 weeks post	71.96 (16.46)	73.81 (18.91)
8 weeks pre	69.30 (17.22)	73.71 (19.01)
8 weeks post	70.36 (17.62)	74.3 (19.05)
16 weeks pre	69.88 (16.5)	68.27 (20.17)
16 weeks post	71.39 (18.33)	70.41 (20.03)
24 weeks pre	72.22 (17.73)	63.27 (20.17)
24 weeks post	73.09 (18.333)	66.27 (19.78)

11. Secondary Outcome

Title	Failure of Standard Therapy
Description	We will assess how many subjects in either arm need escalation of their standard regimen (ie increase in prednisone) during the 16 weeks.
Time Frame	Baseline to 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Concomitant Levaquin, Ethambutol, Azithromycin and Rifampin	Placebo
Arm/Group Description	Levofloxacin 500mg po QD; Ethambutol 1200mg po QD; Azithromycin 250 mg po QD; Rifampin 600mg po QD or Rifabutin 300mg po QD Levofloxacin Ethambutol Azithromycin Rifampin	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. Placebo: This will serve as a placebo to the antibiotics used in antimycobacterial therapy.
Measure Participants	43	48
Count of Participants [Participants]	3 6.1%	2 4.2%

12. Secondary Outcome

Title	Abnormal Lab Values
Description	Safety profile of regimen as evidenced by the number of abnormal lab values classified as Adverse Events
Time Frame	baseline to 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Concomitant Levaquin, Ethambutol, Azithromycin and Rifampin	Placebo
Arm/Group Description	Levofloxacin 500mg po QD; Ethambutol 1200mg po QD; Azithromycin 250 mg po QD; Rifampin 600mg po QD or Rifabutin 300mg po QD Levofloxacin Ethambutol Azithromycin Rifampin	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. Placebo: This will serve as a placebo to the antibiotics used in antimycobacterial therapy.
Measure Participants	49	48
low platelet count	1 2%	0 0%
low WBC count	5 10.2%	0 0%
elevated glucose	3 6.1%	2 4.2%
low glucose	1 2%	1 2.1%

Adverse Events

Time Frame	24 weeks
Arm/Group Title	Concomitant Levaquin, Ethambutol, Azithromycin and Rifampin		Placebo
Arm/Group Description	Levofloxacin 500mg po QD; Ethambutol 1200mg po QD; Azithromycin 250 mg po QD; Rifampin 600mg po QD or Rifabutin 300mg po QD Levofloxacin Ethambutol Azithromycin Rifampin		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. Placebo: This will serve as a placebo to the antibiotics used in antimycobacterial therapy.
All Cause Mortality
	Concomitant Levaquin, Ethambutol, Azithromycin and Rifampin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/49 (0%)		0/48 (0%)
Serious Adverse Events
	Concomitant Levaquin, Ethambutol, Azithromycin and Rifampin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/49 (8.2%)		3/48 (6.3%)
Blood and lymphatic system disorders
Leukopenia	1/49 (2%)	1	0/48 (0%)	0
Cardiac disorders
Hypotension	1/49 (2%)	1	0/48 (0%)	0
Infections and infestations
Sepsis from Abcess	0/49 (0%)	0	1/48 (2.1%)	1
post-operative infection	0/49 (0%)	0	1/48 (2.1%)	1
Nervous system disorders
Neurosarcoidosis	1/49 (2%)	1	0/48 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pneumonia	1/49 (2%)	1	1/48 (2.1%)	1
Other (Not Including Serious) Adverse Events
	Concomitant Levaquin, Ethambutol, Azithromycin and Rifampin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/49 (49%)		16/48 (33.3%)
Blood and lymphatic system disorders
Low Platelet count	1/49 (2%)		0/48 (0%)
Low WBC Count	1/49 (2%)		0/48 (0%)
leukopenia	1/49 (2%)		0/48 (0%)
WBC Low	1/49 (2%)		0/48 (0%)
Low WBC	1/49 (2%)		0/48 (0%)
Cardiac disorders
Hypotension	1/49 (2%)		0/48 (0%)
Ear and labyrinth disorders
Loss of Hearing in Right Ear	0/49 (0%)		1/48 (2.1%)
Endocrine disorders
Elevated Glucose	1/49 (2%)		0/48 (0%)
hypoglycemia	1/49 (2%)		0/48 (0%)
Worsening Glucose	0/49 (0%)		1/48 (2.1%)
hypoglycemia	0/49 (0%)		1/48 (2.1%)
elevated glucose	0/49 (0%)		1/48 (2.1%)
Eye disorders
Floater/Blurry Vision	1/49 (2%)		0/48 (0%)
Eyes red & draining	0/49 (0%)		1/48 (2.1%)
Gastrointestinal disorders
diarrhea	1/49 (2%)		0/48 (0%)
loss of appetite	1/49 (2%)		0/48 (0%)
weakness	1/49 (2%)		0/48 (0%)
nausea	1/49 (2%)		0/48 (0%)
diarrhea/loose stool	1/49 (2%)		0/48 (0%)
Nausea, Vomiting, Diarrhea	1/49 (2%)		0/48 (0%)
Nauseated, Vomiting & Diarrhea	1/49 (2%)		0/48 (0%)
nausea, vomitting, diarrhea	1/49 (2%)		0/48 (0%)
Surgey (Appendectomy)	0/49 (0%)		1/48 (2.1%)
Nausea & Diarrhea	0/49 (0%)		1/48 (2.1%)
Diarrhea, loss of appetite,	0/49 (0%)		1/48 (2.1%)
General disorders
Fever, Nausea, Chills	1/49 (2%)		0/48 (0%)
Fever	1/49 (2%)		0/48 (0%)
increase in hair loss	1/49 (2%)		0/48 (0%)
Fatigue	1/49 (2%)		0/48 (0%)
Insomnia	1/49 (2%)		0/48 (0%)
Urine Color change	1/49 (2%)		0/48 (0%)
Tiredness/Fatigue	1/49 (2%)		0/48 (0%)
flu-like symptoms (chills, aches, fatigue)	1/49 (2%)		0/48 (0%)
Dehydration	1/49 (2%)		0/48 (0%)
Hospitalization	1/49 (2%)		0/48 (0%)
Right Upper Quadant Pain	1/49 (2%)		0/48 (0%)
fever, chills	1/49 (2%)		0/48 (0%)
Pruritus	0/49 (0%)		1/48 (2.1%)
Chills	0/49 (0%)		1/48 (2.1%)
Tiredness	0/49 (0%)		1/48 (2.1%)
Hard to swallow	0/49 (0%)		1/48 (2.1%)
Hepatobiliary disorders
elevated LFTs	1/49 (2%)		0/48 (0%)
Infections and infestations
yeast infection	1/49 (2%)		0/48 (0%)
Shingles	1/49 (2%)		0/48 (0%)
Pneumonia	1/49 (2%)		0/48 (0%)
Yeast Infection, (Urine Urgency, Fever, Joint Aches)	1/49 (2%)		0/48 (0%)
Foot Abscess	0/49 (0%)		1/48 (2.1%)
Sinus Infection	0/49 (0%)		1/48 (2.1%)
Injury, poisoning and procedural complications
Reaction to medication	1/49 (2%)		0/48 (0%)
Ankle Fracture	1/49 (2%)		0/48 (0%)
broken foot and fibula	0/49 (0%)		1/48 (2.1%)
Musculoskeletal and connective tissue disorders
joint pain and achiness	1/49 (2%)		0/48 (0%)
Joint Stiffiness	1/49 (2%)		0/48 (0%)
Joint pain	1/49 (2%)		0/48 (0%)
Shoulder Pain	0/49 (0%)		1/48 (2.1%)
muscle/flank/joint pain	0/49 (0%)		1/48 (2.1%)
Nervous system disorders
Syncope	1/49 (2%)		0/48 (0%)
confusion	1/49 (2%)		0/48 (0%)
Psychiatric disorders
depression	1/49 (2%)		0/48 (0%)
Anxiety	1/49 (2%)		0/48 (0%)
Anxiety, Insomnia	1/49 (2%)		0/48 (0%)
Renal and urinary disorders
Kidney stone pain	0/49 (0%)		1/48 (2.1%)
Respiratory, thoracic and mediastinal disorders
SOB/Fatigue	1/49 (2%)		0/48 (0%)
Cough, fever chills, pain with breathing	1/49 (2%)		0/48 (0%)
Shortness of breath	0/49 (0%)		1/48 (2.1%)
Bronchitis	0/49 (0%)		1/48 (2.1%)
Elevated Glucose	0/49 (0%)		1/48 (2.1%)
Sinus blockage	0/49 (0%)		1/48 (2.1%)
lung infection	0/49 (0%)		1/48 (2.1%)
cough, wheeze, congestion	0/49 (0%)		1/48 (2.1%)
Skin and subcutaneous tissue disorders
Rash	1/49 (2%)		0/48 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.