Moxifloxacin As Part of a Multi-Drug Regimen For Tuberculosis

• ClinicalTrials.gov Identifier: NCT00082173
• Recruitment Status: Completed
• First Posted: May 4, 2004
• Results First Posted: May 22, 2013
• Last Update Posted: May 22, 2013
• Sponsor: Johns Hopkins University
• Information provided by: Johns Hopkins University

Tracking Information

• First Submitted Date: April 30, 2004
• First Posted Date: May 4, 2004
• Results First Submitted Date: March 26, 2013
• Results First Posted Date: May 22, 2013
• Last Update Posted Date: May 22, 2013
• Study Start Date: October 2004
• Actual Primary Completion Date: September 2007 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 26, 2013)

Proportion of Patients With Sterile Sputum Cultures [ Time Frame: 8 weeks ]

Proportion of patients with sterile sputum cultures

• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: March 26, 2013)

Proportion of Patients With Grade 3 or 4 Adverse Reactions Attributable to Study Medications [ Time Frame: 8 weeks ]

Proportion of patients with Grade 3 or 4 adverse reactions attributable to study medications

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Moxifloxacin As Part of a Multi-Drug Regimen For Tuberculosis
• Official Title: Phase 2 Randomized Trial of a Moxifloxacin-Containing Regimen For Treatment of Smear-Positive Pulmonary Tuberculosis in Adults With and Without HIV Infection
• Brief Summary: Current treatment of tuberculosis (TB) requires patients to take four drugs for 8 weeks and then two drugs for 4 months. New drug regimens that are shorter and effective against drug-resistant TB are needed. This study will evaluate whether using the drug moxifloxacin (MOX) in place of ethambutol (EMB) during the first 8 weeks of treatment will effectively treat TB.

Detailed Description

Approximately one-third of the world's population is infected with Mycoplasma tuberculosis; 7 to 8 million new cases of active TB occur each year. TB is the second most common infectious cause of death worldwide. Appropriate treatment of persons with active TB is very important in limiting the transmission of M. tuberculosis and preventing TB-related mortality. Current therapy requires 6 months of a four-drug regimen of isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and EMB.

The development of alternative regimens is a priority, and new classes of antituberculosis agents are needed to provide treatment options for patients with drug-resistant disease. This study will evaluate the effectiveness of replacing EMB with MOX in a multi-drug regimen in the initial phase of treatment of smear-positive pulmonary TB in patients with and without HIV infection.

Participants in this study will be randomly assigned to receive either a MOX-containing drug regimen or the standard EMB-containing drug regimen for 8 weeks. Participants will have study visits weekly during these 8 weeks. After 8 weeks, participants will discontinue MOX, EMB, and PZA and will continue taking INH and RFP for 4 months. Participants will have study visits at Months 4, 6, 12, and 18. Study visits will include a medical interview, physical exam, blood and urine tests, and sputum tests for TB.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Tuberculosis

Intervention

Drug: Moxifloxacin

400mg daily for 8 weeks

Other Name: Avelox

Study Arms

• Experimental: 1
  INH 300mg/RIF 600mg/PZA 20mg/kg/MOX 400mg/EMB placebo once daily for 8 weeks
  Intervention: Drug: Moxifloxacin
• Placebo Comparator: 2
  INH 300mg/RIF 600mg/PZA 20mg/kg/MOX placebo/EMB 15-20mg/kg once daily for 8 weeks
  Intervention: Drug: Moxifloxacin

• Publications *: Conde MB, Efron A, Loredo C, De Souza GR, Graca NP, Cezar MC, Ram M, Chaudhary MA, Bishai WR, Kritski AL, Chaisson RE. Moxifloxacin versus ethambutol in the initial treatment of tuberculosis: a double-blind, randomised, controlled phase II trial. Lancet. 2009 Apr 4;373(9670):1183-9. doi: 10.1016/S0140-6736(09)60333-0.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 23, 2005): 170
• Original Enrollment: Same as current
• Actual Study Completion Date: September 2008
• Actual Primary Completion Date: September 2007 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Presumptive diagnosis of smear-positive pulmonary TB within 2 weeks of study entry. Patients with both pulmonary and extrapulmonary disease are eligible.
• Documentation of HIV infection status. If HIV status is unknown at study entry, the participant must consent to testing and results must be available prior to study participation.
• Agree to use acceptable methods of contraception

Exclusion Criteria:

• History of adverse drug reaction to MOX, INH, RIF, PZA, or EMB
• Disease or condition for which MOX, INH, RIF, PZA, or EMB is contraindicated
• History of more than 14 days of continuous antituberculosis therapy during the previous 2 years or more than 2 months of antituberculosis therapy ever
• Active AIDS-related opportunistic infection or malignancy
• Currently receiving or planning to receive HIV protease inhibitors or nonnucleoside reverse transcriptase inhibitors in the first 2 months after study entry
• Silicotuberculosis
• Central nervous system TB
• Pregnant or breastfeeding
• Unable to take oral medication
• Electrocardiogram (EKG) QTc interval greater than 450 msec
• Taking classes IA or III antiarrhythmic agents (quinidine, procainamide, amiodarone, sotalol), cisapride, erythromycin, perphenazine/amitriptyline, phenothiazines, or tricyclic antidepressant
• Diseases or conditions for which treatment with other drugs with antituberculosis activity (e.g., rifabutin for MAC prophylaxis) is anticipated during the course of the study

Sex/Gender

• Sexes Eligible for Study: All

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

Administrative Information

• NCT Number: NCT00082173
• Other Study ID Numbers: FD-R-002135-01
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Dr. Richard E. Chaisson, Johns Hopkins University
• Original Responsible Party: Not Provided
• Current Study Sponsor: Johns Hopkins University
• Original Study Sponsor: Food and Drug Administration (FDA)
• Collaborators: Not Provided

Investigators

• Principal Investigator: Richard E. Chaisson, MD; Johns Hopkins University

• PRS Account: Johns Hopkins University
• Verification Date: March 2013