TBTC Study 31: Rifapentine-containing Tuberculosis Treatment Shortening Regimens
Condition: Tuberculosis
MeSH terms: Tuberculosis
Intervention: rifapentine; rifapentine and moxifloxacin; control
Intervention description: Regimen 2: Rifapentine is substituted for rifampin as the basis of 4-month treatment; Regimen 3: In addition to the single substitution described for regimen 2, a second substitution is added, of moxifloxacin for ethambutol.; standard six-month treatment
Intervention MeSH terms: Moxifloxacin; Rifapentine; Rifampin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 2516.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to determine whether one or two four-month regimens of
      tuberculosis treatment are as effective as a standard six-month regimen for treatment of
      pulmonary tuberculosis (TB). All three regimens are administered daily, seven days each week,
      with direct observation of each dose by a health-care worker at least five of the seven days
      of each week.

      The standard six-month regimen is two months of isoniazid, rifampin, ethambutol, and
      pyrazinamide followed by four months of isoniazid and rifampin.

      The first short regimen is a single substitution of rifapentine for rifampin: two months of
      isoniazid, rifapentine, ethambutol, and pyrazinamide, followed by two months of isoniazid and
      rifapentine.

      The second short regimen is a double substitution of rifapentine for rifampin and
      moxifloxacin for ethambutol: two months of isoniazid, rifapentine, moxifloxacin, and
      pyrazinamide, followed by two months of isoniazid, rifapentine, and moxifloxacin.

      Target enrollment is 2500 participants. Each study participant will remain in the study for
      18 months in order to include at least 12 months of evaluation of whether the participant's
      TB recurs.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Suspected pulmonary tuberculosis plus one or both of the following: a) at least one
             sputum specimen positive for acid-fast bacilli on smear microscopy OR b) at least one
             sputum specimen positive for M. tuberculosis by Xpert MTB/RIF testing, with
             semiquantitative result of 'medium' or 'high' and rifamycin resistance not detected.

          -  Age twelve (12) years or older

          -  A verifiable address or residence location that is readily accessible for visiting,
             and willingness to inform the study team of any change of address during the treatment
             and follow-up period.

          -  Women of child-bearing potential who are not surgically sterilized must agree to
             practice a barrier method of contraception or abstain from heterosexual intercourse
             during study drug treatment.

          -  Documentation of HIV infection status.

          -  For HIV-positive individuals, CD4 T cell count greater than or equal to 100 cells/mm3
             based on testing performed at or within 30 days prior to screening.

          -  Laboratory parameters done at or within 14 days prior to screening:

               -  Serum or plasma alanine aminotransferase (ALT) less than or equal to 3 times the
                  upper limit of normal

               -  Serum or plasma total bilirubin less than or equal to 2.5 times the upper limit
                  of normal

               -  Serum or plasma creatinine level less than or equal to 2 times the upper limit of
                  normal

               -  Serum or plasma potassium level greater than or equal to 3.5 meq/L

               -  Hemoglobin level of 7.0 g/dL or greater

               -  Platelet count of 100,000/mm3 or greater

          -  For women of childbearing potential, a negative pregnancy test at or within seven (7)
             days prior to screening

          -  Karnofsky score greater than or equal to 60

          -  Written informed consent

        Exclusion Criteria:

          -  Pregnant or breast-feeding.

          -  Unable to take oral medications.

          -  Previously enrolled in this study.

          -  Received any investigational drug in the past 3 months.

          -  More than five (5) days of treatment directed against active tuberculosis within 6
             months preceding initiation of study drugs.

          -  More than five (5) days of systemic treatment with any one or more of the following
             drugs within 30 days preceding initiation of study drugs: isoniazid, rifampin,
             rifabutin, rifapentine, ethambutol, pyrazinamide, kanamycin, amikacin, streptomycin,
             capreomycin, moxifloxacin, levofloxacin, gatifloxacin, ofloxacin, ciprofloxacin, other
             fluoroquinolones, ethionamide, prothionamide, cycloserine, terizidone,
             para-aminosalicylic acid, linezolid, clofazimine, delamanid or bedaquiline.

          -  Known history of prolonged QT syndrome.

          -  Suspected or documented tuberculosis involving the central nervous system and/or bones
             and/or joints, and/or miliary tuberculosis and/or pericardial tuberculosis.

          -  Current or planned use within six months following enrollment of one or more of the
             following medications: HIV protease inhibitors, HIV integrase inhibitors, HIV entry
             and fusion inhibitors, HIV non-nucleoside reverse transcriptase inhibitors other than
             efavirenz, quinidine, procainamide, amiodarone, sotalol, disopyramide, ziprasidone, or
             terfenadine. Individuals who are currently taking efavirenz-based antiretroviral
             treatment or for whom initiation of efavirenz-based antiretroviral treatment is
             planned within 17 weeks following enrollment may participate.

          -  Weight less than 40.0 kg.

          -  Known allergy or intolerance to any of the study medications.

          -  Individuals will be excluded from enrollment if, at the time of enrollment, their M.
             tuberculosis isolate is already known to be resistant to any one or more of the
             following: rifampin, isoniazid, pyrazinamide, ethambutol, or fluoroquinolones.

          -  Other medical conditions, that, in the investigator's judgment, make study
             participation not in the individual's best interest.

          -  Current or planned incarceration or other involuntary detention.