StAT-TB (Statin Adjunctive Therapy for TB): A Phase 2b Dose-finding Study of Pravastatin in Adults With Tuberculosis
Condition: Tuberculosis; Pulmonary Tuberculosis
MeSH terms: Tuberculosis; Tuberculosis, Pulmonary
Intervention: Pravastatin; Rifafour; Vitamin B6
Intervention description: Tablets, administered orally; Fixed-dose combination (isoniazid, rifampin, pyrazinamide, and ethambutol) tablets, administered orally; Administered orally.
Intervention MeSH terms: Vitamin B 6; Pyridoxal; Pyridoxine; Pravastatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to assess the safety, tolerability, and pharmacokinetics of
      pravastatin adjunctive therapy when combined with the standard tuberculosis (TB) treatment
      regimen in adults with TB.
    

Eligibility criteria:

        Inclusion Criteria:

          -  18 years of age or older

          -  Clinical signs and symptoms of pulmonary tuberculosis

          -  Abnormal chest radiograph consistent with pulmonary tuberculosis

          -  At least one sputum positive for M. tuberculosis by Xpert MTB/RIF with a cycle
             threshold (Ct) less than 28.

          -  Documentation of HIV status

          -  Weight greater than or equal to 45 kg

          -  Karnofsky score of at least 60

          -  Ability to provide informed consent

          -  Ability to adhere to study follow-up visits

          -  Negative pregnancy test in women of child-bearing age

          -  Ability to adhere to contraceptive requirements and willing to use two forms of
             contraception: 1) a double barrier method to prevent pregnancy (i.e. use of a condom
             with either diaphragm or cervical cap) or 2) use of an intrauterine device in
             combination with a barrier contraceptive. The participant must be willing to continue
             these contraceptive measures throughout the duration of the study and until one week
             after the last dose of study medication or one week after discontinuation from study
             medication in case of premature discontinuation.

          -  Five days or fewer of anti-tuberculosis treatment within the previous 3 months

        Exclusion Criteria:

          -  A history of severe adverse reactions to any statin or any other study agent or
             contraindications to use of statins.

          -  Current use of statins or other lipid-lower agents;

          -  Clinical indication for statin therapy based on cardiovascular risk:

               -  Familial hypercholesterolemia

               -  Previous history of myocardial infarction or stroke

          -  For HIV-positive individuals, a CD4+ T-cell count less than 350/mm^3

          -  Use of antiretroviral drugs

          -  Hemoglobin concentration less than 8 g/dL;

          -  Baseline creatinine kinase elevation more than three times the upper limit of normal

          -  Abnormal baseline laboratory values

               -  Baseline alanine aminotransferase (ALT) concentration more than 2.5 times the
                  upper limit of normal (Grade 1)

               -  Serum creatinine concentration more than twice the upper limit of normal;

               -  Serum total bilirubin level greater than twice the upper limit of normal

               -  Platelet count less than 100,000/mm^3

               -  Absolute neutrophil count (ANC) less than 1,000/mm^3

          -  Pregnant or breastfeeding;

          -  Silico-tuberculosis.

          -  Currently receiving TB treatment

          -  Serologies or PCR positive for viral hepatitis (Hepatitis, B, C)

          -  Concomitant disorders or conditions for which isoniazid, rifampin, pyrazinamide, or
             ethambutol is contraindicated. These include cirrhosis, acute liver disease of any
             cause, acute uncontrolled gouty arthritis and peripheral neuropathy.

          -  Any medical or psychological condition which, in the view of the study investigator,
             makes study participation inadvisable.

          -  Infection with an isolate determined to be resistant to rifampin by GeneXpert.

          -  More than five days of anti-tuberculosis treatment within the previous 3 months

          -  Planned or current use of cyclosporine, tacrolimus, erythromycin or colchicine

          -  Central nervous system (CNS) TB

          -  Extra-pulmonary TB only, not in combination with pulmonary TB

          -  History of TB