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Moxifloxacin As Part of a Multi-Drug Regimen For Tuberculosis

Primary Purpose

Tuberculosis

Status
Completed
Phase
Phase 2
Locations
Brazil
Study Type
Interventional
Intervention
Moxifloxacin
Sponsored by
Johns Hopkins University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Tuberculosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Clementino Fraga Filho Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

1

2

Arm Description

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

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

Outcomes

Primary Outcome Measures

Proportion of Patients With Sterile Sputum Cultures
Proportion of patients with sterile sputum cultures

Secondary Outcome Measures

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

Full Information

First Posted
April 30, 2004
Last Updated
March 26, 2013
Sponsor
Johns Hopkins University
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1. Study Identification

Unique Protocol Identification Number
NCT00082173
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2013
Overall Recruitment Status
Completed
Study Start Date
October 2004 (undefined)
Primary Completion Date
September 2007 (Actual)
Study Completion Date
September 2008 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Johns Hopkins University

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tuberculosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
170 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
INH 300mg/RIF 600mg/PZA 20mg/kg/MOX 400mg/EMB placebo once daily for 8 weeks
Arm Title
2
Arm Type
Placebo Comparator
Arm Description
INH 300mg/RIF 600mg/PZA 20mg/kg/MOX placebo/EMB 15-20mg/kg once daily for 8 weeks
Intervention Type
Drug
Intervention Name(s)
Moxifloxacin
Other Intervention Name(s)
Avelox
Intervention Description
400mg daily for 8 weeks
Primary Outcome Measure Information:
Title
Proportion of Patients With Sterile Sputum Cultures
Description
Proportion of patients with sterile sputum cultures
Time Frame
8 weeks
Secondary Outcome Measure Information:
Title
Proportion of Patients With Grade 3 or 4 Adverse Reactions Attributable to Study Medications
Description
Proportion of patients with Grade 3 or 4 adverse reactions attributable to study medications
Time Frame
8 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Richard E. Chaisson, MD
Organizational Affiliation
Johns Hopkins University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Clementino Fraga Filho Hospital
City
Rio de Janeiro
Country
Brazil

12. IPD Sharing Statement

Citations:
PubMed Identifier
19345831
Citation
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.
Results Reference
derived

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Moxifloxacin As Part of a Multi-Drug Regimen For Tuberculosis

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