Tuberculosis
Conditions
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.
Interventions
DRUGMoxifloxacin
400mg daily for 8 weeks
Sponsors
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients With Sterile Sputum Cultures | 8 weeks | Proportion of patients with sterile sputum cultures |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients With Grade 3 or 4 Adverse Reactions Attributable to Study Medications | 8 weeks | Proportion of patients with Grade 3 or 4 adverse reactions attributable to study medications |
Countries
Brazil
Participant flow
Recruitment details
Subjects with respiratory symptoms suggestive of TB were recruited from the HUCFF outpatient TB clinic as well as other local TB clinics.
Pre-assignment details
Patients who did not meet enrollment criteria or who did not want to participate in the study were excluded.
Participants by arm
| Arm | Count |
|---|---|
| Experimental Arm (Moxi) | 74 |
| Control Arm (EMB) | 72 |
| Total | 146 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Culture negative or resistant at baselin | 5 | 6 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 5 |
Baseline characteristics
| Characteristic | Control Arm (EMB) | Experimental Arm (Moxi) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 2 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 71 Participants | 72 Participants | 143 Participants |
| Age Continuous | 35.7 years STANDARD_DEVIATION 12 | 32.5 years STANDARD_DEVIATION 11.7 | 34.1 years STANDARD_DEVIATION 11.9 |
| Region of Enrollment Brazil | 72 participants | 74 participants | 146 participants |
| Sex: Female, Male Female | 22 Participants | 34 Participants | 56 Participants |
| Sex: Female, Male Male | 50 Participants | 40 Participants | 90 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 74 | 0 / 72 |
| serious Total, serious adverse events | 6 / 74 | 6 / 72 |
Outcome results
Primary
Proportion of Patients With Sterile Sputum Cultures
Proportion of patients with sterile sputum cultures
Time frame: 8 weeks
Population: Proportion of patients with sterile sputum cultures at week 8
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Experimental Arm | Proportion of Patients With Sterile Sputum Cultures | 59 Participants |
| Control Arm | Proportion of Patients With Sterile Sputum Cultures | 45 Participants |
Secondary
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
Time frame: 8 weeks
Population: DAIDS Table of Adverse Events
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Experimental Arm | Proportion of Patients With Grade 3 or 4 Adverse Reactions Attributable to Study Medications | 0 Participants |
| Control Arm | Proportion of Patients With Grade 3 or 4 Adverse Reactions Attributable to Study Medications | 0 Participants |