Moxifloxacin As Part of a Multi-Drug Regimen For Tuberculosis

NCT ID: NCT00082173

Last Updated: 2013-05-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 170 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-10-31
• Study Completion Date: 2008-09-30

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.

Conditions

Tuberculosis

Study Design

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

Study Groups

1

INH 300mg/RIF 600mg/PZA 20mg/kg/MOX 400mg/EMB placebo once daily for 8 weeks

Group Type: EXPERIMENTAL

Moxifloxacin

Intervention Type: DRUG

400mg daily for 8 weeks

2

INH 300mg/RIF 600mg/PZA 20mg/kg/MOX placebo/EMB 15-20mg/kg once daily for 8 weeks

Group Type: PLACEBO_COMPARATOR

Moxifloxacin

Intervention Type: DRUG

400mg daily for 8 weeks

Interventions

Moxifloxacin

400mg daily for 8 weeks

Intervention Type: DRUG

Other Intervention Names

Avelox

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

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

Sponsors

Johns Hopkins University

OTHER

Sponsor Role: lead

Responsible Party

Johns Hopkins University

Principal Investigators

Richard E. Chaisson, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

Clementino Fraga Filho Hospital

Rio de Janeiro, Rio de Janeiro, Brazil

Countries

Brazil

References

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.

Reference Type: DERIVED

PMID: 19345831 (View on PubMed)

Other Identifiers

FD-R-002135-01

Identifier Type: -

Identifier Source: org_study_id