Rifapentine Plus Moxifloxacin for Treatment of Pulmonary Tuberculosis
Condition: Tuberculosis
MeSH terms: Tuberculosis; Tuberculosis, Pulmonary
Intervention: Rifapentine, Moxifloxacin, Pyrazinamide, Isoniazid; Isoniazid, Rifampin, Pyrazinamide, Ethambutol
Intervention description: 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.; Administered per standard of care for TB treatment
Intervention MeSH terms: Moxifloxacin; Rifampin; Isoniazid; Pyrazinamide; Ethambutol; Rifapentine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 121.0
Sex: All
Minimum age: 18 Years
Maximum age: 100 Years
Healthy volunteers: No
Keywords: Tuberculosis; Moxifloxacin; Rifapentine

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.
    

Eligibility criteria:

        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.