Shortened Regimen for Drug-susceptible TB in Children
While drug-susceptible tuberculosis (TB) disease in children currently requires four to six months of treatment, most children may be able to be cured with a shorter treatment of more powerful drugs. Shorter treatment may be easier for children to tolerate and finish as well as ease caregiver strain from managing treatment side effects and supporting children over many months. The primary objective of this study is to evaluate if a 2-month regimen (including isoniazid (H), rifapentine (P), pyrazinamide (Z) and moxifloxacin (M)) is as safe and effective as a 4- to 6-month regimen (isoniazid, rifampicin (R), pyrazinamide, ethambutol (E)) in curing drug-susceptible TB disease in children under 10 years old. The study is also evaluating the safety of the HPZM in children with and without HIV.
• Parent or guardian is willing and able to provide written informed consent for potential participant's study participation; in addition, when applicable per Ethics Committee/Institutional Review Board (EC/IRB) policies and procedures, potential participant is willing and able to provide assent for study participation.
• At Entry, age of less than 10 years.
• At Entry, weight 3 kilograms (kg) or greater.
• At Entry, diagnosed with TB disease, defined as:
‣ Pulmonary (including pleural effusion) and/or lymph node (extra-thoracic and/or intra-thoracic) TB with or without bacteriologic confirmation;
⁃ Clinician has decided to treat with standard first-line drug-susceptible TB regimen.
• Known HIV status or HIV testing in progress based on meeting testing requirements.
• Has normal, Grade 1 or 2 test results for all of the following done at or within 14 days of Entry (including the most recent):
‣ Alanine aminotransferase (ALT) less than or equal to 5 times the upper limit of normal;
⁃ Total bilirubin less than or equal to 2.5 times the upper limit of normal;
⁃ Potassium level of 3.0 milliequivalent/L or greater;
⁃ Hemoglobin level of 7.0 g/dL or greater;
⁃ Platelet count of 100,000/mm3 or greater;
⁃ Estimated glomerular filtration rate (eGFR; bedside Schwartz formula) 60 mL/min/1.73m2 or higher.
• For children living with HIV:
‣ On antiretroviral therapy (ART) at Entry: Must be on, or able to be switched to a dolutegravir-based regimen at or prior to Entry;
⁃ Not on ART at Entry: Planned initiation of dolutegravir before or at study Week 4.
• For participants who have reached menarche or who are engaging in sexual activity (self-reported): negative serum or urine pregnancy test within 7 days of Entry.
• For participants who are engaging in sexual activity that could lead to pregnancy (self-reported): agrees to practice at least one non-hormonal method of contraception or abstain from heterosexual intercourse during study drug treatment and for 30 days after stopping study medications. Non-hormonal methods include:
‣ Male or female condoms
⁃ Diaphragm or cervical cap (with spermicide, if available)
⁃ Non-hormonal intrauterine device (IUD) or intrauterine system (IUS)
• At Entry, intends to remain in the catchment area of the study site for the duration of study follow-up or willingness to be followed up beyond the catchment area if/when applicable, as determined by the site investigator based on participant/parent/guardian report.