Using Biomarkers to Predict TB Treatment Duration

• Status: Active, not recruiting
• Trial end date: 2022-12-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Treatments: Ethambutol; Isoniazid; Pyrazinamide; Rifampin

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