Moxifloxacin As Part of a Multi-Drug Regimen For Tuberculosis

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Tuberculosis

Intervention / Treatment
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* Drug: Moxifloxacin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 |