Moxifloxacin As Part of a Multi-Drug Regimen For Tuberculosis

Phase 2 Randomized Trial of a Moxifloxacin-Containing Regimen For Treatment of Smear-Positive Pulmonary Tuberculosis in Adults With and Without HIV Infection

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.

Study Overview

• Status: Completed
• Conditions: Tuberculosis
• Intervention / Treatment: Drug: Moxifloxacin

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
• Enrollment (Actual): 170
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • Rio de Janeiro, Brazil
    • Clementino Fraga Filho Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; INH 300mg/RIF 600mg/PZA 20mg/kg/MOX 400mg/EMB placebo once daily for 8 weeks	Drug: Moxifloxacin; 400mg daily for 8 weeks; Other Names: Avelox
Placebo Comparator: 2; INH 300mg/RIF 600mg/PZA 20mg/kg/MOX placebo/EMB 15-20mg/kg once daily for 8 weeks	Drug: Moxifloxacin; 400mg daily for 8 weeks; Other Names: Avelox

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Patients With Sterile Sputum Cultures	Proportion of patients with sterile sputum cultures	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Patients With Grade 3 or 4 Adverse Reactions Attributable to Study Medications	Proportion of patients with Grade 3 or 4 adverse reactions attributable to study medications	8 weeks

Collaborators and Investigators

• Sponsor: Johns Hopkins University

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2004
• Primary Completion (Actual): September 1, 2007
• Study Completion (Actual): September 1, 2008

Study Registration Dates

• First Submitted: April 30, 2004
• First Submitted That Met QC Criteria: May 3, 2004
• First Posted (Estimate): May 4, 2004

Study Record Updates

• Last Update Posted (Estimate): May 22, 2013
• Last Update Submitted That Met QC Criteria: March 26, 2013
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Moxifloxacin
• Other Study ID Numbers: FD-R-002135-01