Tuberculosis
Conditions
Keywords
Tuberculosis, Moxifloxacin, Rifapentine
Brief summary
Although effective therapy for tuberculosis is available, TB continues to cause significant problems worldwide, and rates of multi-drug resistant (MDR) TB cases are on the rise. A major obstacle to the control of TB is poor adherence with lengthy (usually 6 months) and complicated treatment regimens. Incomplete TB treatment can lead to serious consequences such as increased severity of illness and death, prolonged infectiousness and transmission in the community, and the development of drug resistance. The development of new treatment strategies with more stronger drugs could lead to shorter and simpler regimens. A TB treatment regimen that allowed treatment duration to be meaningfully decreased would have important public health implications. This trial will compare the effect and safety of a new oral regimen to that of the standard regimen for the first phase of treatment for pulmonary tuberculosis. The experimental regimen will consist of the following: * Two months of isoniazid, rifapentine, pyrazinamide and moxifloxacin (HPZM) administered once daily. Pyridoxine (vitamin B6) will be given with each dose of isoniazid. The standard control intensive phase regimen will consist of the following: * Two months of isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE) administered once daily. Pyridoxine (vitamin B6) will be given with each dose of isoniazid. Following intensive phase therapy (the study phase), all patients will be treated with a non-experimental continuation phase regimen. In mice, the combination of Moxifloxacin and Rifapentine have cured the animals significantly faster than the standard regimen and this study will be the first step to see if the potential is also there in humans.
Interventions
DRUGRifapentine, Moxifloxacin, Pyrazinamide, Isoniazid
Rifapentine:150mg tablets, dose = 300mg for subjects \<= 45kg and 450mg for those \>45kg by mouth once a day for 8 weeks; Moxifloxacin 400mg tablet by mouth once a day for 8 weeks, Isoniazid and Pyrazinamide per standard of care for TB treatment.
DRUGIsoniazid, Rifampin, Pyrazinamide, Ethambutol
Administered per standard of care for TB treatment
Sponsors
Universidade Federal do Rio de Janeiro
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* Presumptive diagnosis of sputum smear-positive pulmonary TB. * Age: ≥18 years * Seven (7) or fewer days of multidrug therapy for TB disease in the preceding 6 months. * Seven (7) or fewer days of fluoroquinolone therapy in the preceding 3 months. * Documentation of HIV infection status. * For HIV seropositive individuals, a CD4 T lymphocyte count of greater than or equal to 200 cells/mm3. * Documentation of study baseline laboratory parameters done at, or ≤ 14 days prior to screening: * AST less than or equal to 2.5 times upper limit of normal. * Total bilirubin level less than 2.5 times upper limit of normal. * Creatinine level less than 2 times upper limit of normal. * Hemoglobin level of at least 8.0 g/dl. * Platelet count of at least 75,000 mm3. * Potassium level of at least 3.5. * Negative pregnancy test (women of childbearing potential). * Karnofsky score of at least 60 (requires occasional assistance but is able to care for most of his/her needs). * Male or nonpregnant, nonnursing female. * Provision of informed consent.
Exclusion criteria
* CD4 count \< 200 cells/cu mm. * Presence of active AIDS-related opportunistic infection (other than TB) or active AIDS-related malignancy. * Known intolerance to any of the study drugs. * Concomitant disorders or conditions for which any of the study drugs is contraindicated. These include severe hepatic damage, acute liver disease of any cause, and acute uncontrolled gouty arthritis. * Inability to take oral medication. * Central nervous system TB. * Pulmonary silicosis. * Current or planned therapy, during study phase (intensive phase of TB treatment), with any one or more of the following drugs: quinidine, procainamide, amiodarone, sotalol, disopyramide, terfenadine, cisapride, erythromycin, clarithromycin, phenothiazines, haloperidol, olanzapine, ziprasidone, tricyclic antidepressants, chronic corticosteroids administered either orally or intravenously, chronic fluconazole,chronic itraconazole, chronic ketoconazole, oral or intravenous tacrolimus, oral or intravenous cyclosporine, HIV protease inhibitor, HIV non-nucleoside reverse transcriptase inhibitor. * Concurrent severe and/or uncontrolled medical or psychiatric condition that, in the opinion of the investigator, could cause unacceptable safety risks or compromise compliance with the protocol. * Unable or unwilling to receive directly observed therapy and/or adhere with follow-up (e.g. due to residence remote from the study site). * Refusal of consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To Compare, by Treatment Group, the Percentage of Patients With a Negative Sputum Culture at the End of Intensive Phase Therapy. | Week 8 | LJ culture conversion |
| To Compare the Safety and Tolerability of the 2 Intensive Phase Regimens. | Weekly or more frequent | Study was prematurely terminated and data was not collected for this outcome measure. |
Countries
Brazil
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| HPZM Two months of isoniazid, rifapentine, pyrazinamide and moxifloxacin (HPZM) administered once daily. Pyridoxine (vitamin B6) will be given with each dose of isoniazid.
Rifapentine, Moxifloxacin, Pyrazinamide, Isoniazid: Rifapentine:150mg tablets, dose = 300mg for subjects \<= 45kg and 450mg for those \>45kg by mouth once a day for 8 weeks; Moxifloxacin 400mg tablet by mouth once a day for 8 weeks, Isoniazid and Pyrazinamide per standard of care for TB treatment. | 62 |
| HRZE Two months of isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE) administered once daily. Pyridoxine (vitamin B6) will be given with each dose of isoniazid.
Isoniazid, Rifampin, Pyrazinamide, Ethambutol: Administered per standard of care for TB treatment | 59 |
| Total | 121 |
Baseline characteristics
| Characteristic | HPZM | HRZE | Total |
|---|---|---|---|
| Age, Continuous | 33 years | 30 years | 32 years |
| Region of Enrollment Brazil | 62 participants | 59 participants | 121 participants |
| Sex: Female, Male Female | 47 Participants | 36 Participants | 83 Participants |
| Sex: Female, Male Male | 15 Participants | 23 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 62 | 6 / 59 |
| serious Total, serious adverse events | 0 / 62 | 0 / 59 |
Outcome results
Primary
To Compare, by Treatment Group, the Percentage of Patients With a Negative Sputum Culture at the End of Intensive Phase Therapy.
LJ culture conversion
Time frame: Week 8
Population: modified intention to treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HPZM | To Compare, by Treatment Group, the Percentage of Patients With a Negative Sputum Culture at the End of Intensive Phase Therapy. | 78.3 percentage of participants |
| HRZE | To Compare, by Treatment Group, the Percentage of Patients With a Negative Sputum Culture at the End of Intensive Phase Therapy. | 84.3 percentage of participants |
Primary
To Compare the Safety and Tolerability of the 2 Intensive Phase Regimens.
Study was prematurely terminated and data was not collected for this outcome measure.
Time frame: Weekly or more frequent