Using Biomarkers to Predict TB Treatment Duration
Condition: Pulmonary Tuberculosis
MeSH terms: Tuberculosis; Tuberculosis, Pulmonary
Intervention: Saliva collection; Urine collection; Sputum collection; Blood Collection; PET/CT Scan; Isoniazid, Rifampicin, Pyrazinamide and Ethambutol
Intervention description: For biomarker assessments; For biomarker assessments; For primary endpoint assessments and other biomarker assessments; For biomarker and eligibility assessments; Imaging of the lungs to establish disease extent and severity; Treatment-standard of care
Intervention MeSH terms: Rifampin; Isoniazid; Pyrazinamide; Ethambutol
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 946.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Drug-Resistance; Heteroresistance; Relapse-markers; Medical Imaging; Treatment-shortening

Summary:

      Background:

      Tuberculosis (TB) is a bacterial lung infection. Typical treatment using anti-TB drugs lasts
      about 6 months. Some people with less severe TB might not need to take the drugs that long.
      Researchers think a PET/CT lung scan along with estimating how much TB is in the lungs might
      show who will be cured after only 4 months of treatment.

      Objective:

      To demonstrate that 4 months of treatment is not inferior to 6 months of treatment for people
      with less severe TB.

      Eligibility:

      People 18-75 years old who have TB treatable with standard TB drugs

      Design:

      Participants will be screened with:

      Medical history

      Physical exam

      Blood and urine tests

      HIV test

      Sputum sample: Participants will be asked to cough sputum into a cup.

      Chest x-ray

      Participants will start TB drugs. They will have visits at weeks 1, 2, 4, 8, 12, and about 6
      more times during the 18-month study. Visits include:

      Sputum samples

      Physical exam

      Blood tests

      PET/CT scans at 2-3 visits: Participants fast for about 6 hours before the scan. Participants
      get FDG, a type of sugar that gives off a small amount of radiation, through an arm vein.
      They lie on a table in a machine that takes pictures of the body.

      Chest x-rays at 1-2 visits

      Participants who we believe are likely to be cured at 4 months will be randomly assigned to
      get either 6 months of treatment or 4 months of treatment.

      Participants may be asked to join a substudy using their sputum samples or additional blood
      tests.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

               1. Age 18 to 75 years with body weight from 35 kg to 90 kg

               2. Has not been treated for active TB within the past 3 years

               3. Not yet on TB treatment

               4. Xpert positive for M.tb

               5. Rifampin-sensitive pulmonary tuberculosis as indicated by Xpert

               6. Laboratory parameters within previous 14 days before enrollment:

                    1. Serum AST and ALT <3x upper limit of normal (ULN)

                    2. Creatinine <2x ULN

                    3. Hemoglobin >7.0 g/dL

                    4. Platelet count >50 x10(9) cells/L

               7. Able and willing to return for follow-up visits

               8. Able and willing to provide informed consent to participate in the study

               9. Willing to undergo an HIV test

              10. At sites with sufficient SARS-CoV-2 testing capacity and personal protective
                  equipment for study staff, willing to undergo COVID-19 testing:

                  viral RNA PCR testing for SARS-CoV-2 to determine active infection and antibody
                  testing for SARS-CoV-2 to determine prior infection

              11. Willing to have samples, including DNA, stored

              12. Willing to consistently practice a highly reliable, non-hormonal method of
                  pregnancy prevention (e.g., condoms) during treatment if participant is a
                  premenopausal female unless she has had a hysterectomy or bilateral tubal
                  ligation or her male partner has had a vasectomy. If hormonal contraception is
                  used an additional method of pregnancy prevention (as above) should be used.

        EXCLUSION CRITERIA:

          1. Clinical suspicion of or confirmed extrapulmonary TB, including pleural TB

          2. Pregnant or desiring/trying to become pregnant in the next 6 months or breastfeeding.

          3. HIV infected

          4. Currently COVID-19 infected

          5. Unable to take oral medications

          6. Diabetes as defined by point of care HbA1c greater than 6.5%, random glucose greater
             than 200 mg/dL (or 11.1 mmol/L), fasting plasma glucose greater than or equal to 126
             mg/dL (or 7.0 mmol/L), or the presence of any antidiabetic agent (including
             traditional medicines) as a concomitant medicine

          7. Disease complications or concomitant illnesses that may compromise safety or
             interpretation of trial endpoints, such as known diagnosis of chronic inflammatory
             condition (e.g. sarcoidosis, rheumatoid arthritis, connective tissue disorder)

          8. Use of immunosuppressive medications, such as TNF-alpha inhibitors or systemic or
             inhaled corticosteroids, within the past 2 weeks

          9. Use of any investigational drug in the previous 3 months

         10. Substance or alcohol abuse that in the opinion of the investigator may interfere with
             the participant's adherence to study procedures.

         11. Any person for whom the physician feels this study is not appropriate