Tuberculosis
Conditions
Interventions
Isoniazid
Sponsors
National Institute of Allergy and Infectious Diseases and National Institute of Child Health and Human Development
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: INDEX CASE Confirmed Pulmonary MDR-TB Men and women age =18 years HOUSEHOLD CONTACTS Children 0 to <5 years of age HIV+ or non-HIV immunosuppressed adults and children =5 years of age TST+ and/or IGRA+ adults and children =5 years of age not HIV+ or non-HIV immunosuppressed For females of reproductive potential, negative serum or urine pregnancy test within 7 days prior to study entry For infants (0 to 1 year of age), weight =2.5 kg at screening Chest radiograph without evidence of active TB performed within 70 days prior to study entry for HHCs =2 years of age and within 30 days prior to study entry for HHCs <2 years of age. QTcF interval =460 ms within 30 days prior to study entry as confirmed by the central ECG reading center Enrollment of the HHC within 30 days after the index case is enrolled.
Exclusion criteria
Exclusion criteria: INDEX CASE Has previously enrolled into the A5300B/I2003B/PHOENIx trial as an index case or HHC, or is a member of a HH which has previously enrolled into the A5300B/I2003B/PHOENIx trial. HOUSEHOLD CONTACT Current confirmed or probable or possible pulmonary or extrapulmonary TB, Receipt of more than 30 cumulative days of INH, rifamycin, fluoroquinolone, or DLM in the 90 days prior to study entry. History of or current liver cirrhosis at any time prior to study entry Evidence of acute hepatitis, such as abdominal pain, nausea and vomiting, jaundice, dark urine, and/or light stools within 90 days prior to study entry Peripheral neuropathy =Grade 2 within 90 days prior to study entry Known allergy/sensitivity or any hypersensitivity to components of study drugs or their formulation Current cardiovascular disorder that is clinically relevant in the opinion of the site investigator Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements Serious illness requiring systemic treatment including parenteral therapy (e.g., antibiotics) and/or hospitalization within 30 days prior to study entry. Currently receiving other medication with potential for adverse drug-drug interactions, including QT prolongation. Taken an investigational drug or vaccine within 30 days prior to study entry. Has a clinical condition that in the site investigator’s opinion would interfere with study participation. Has enrolled into a TB vaccine or TB preventive therapy or TB therapeutic trial, including the A5300B/I2003B/PHOENIx trial in the two years prior to study entry. Not expected to be able to complete 96 weeks of study follow-up
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Efficacy The primary outcome measure is the occurrence of confirmed or probable active TB at any time between Day 0 and the week 96 study visit . This will be evaluated at the individual participant level. An independent outcomes review committee will review diagnoses of active TB made by the participating sites and deaths. This committee will include clinicians who are experts in the diagnosis of TB in adults, adolescents, and children. The committee will not include members who are directly involved with the care of study participants or who are study team members providing participant management guidance to site investigators. The committee will be blinded to treatment assignment. Only confirmed and probable active TB cases that are validated by the independent outcomes review committee will be included in the primary efficacy analysis. The independent outcomes review committee will also determine the date that a HHC first met the criteria for confirmed or probable active TB. Safety The primary safety outcome measure is the permanent discontinuation of randomized study drug (DLM or INH) due to a treatment-related adverse event (i.e., requiring discontinuation, or in the opinion of the site investigator is a treatment-limiting adverse event). This will be evaluated at the individual participant level. | — |
Secondary
| Measure | Time frame |
|---|---|
| Efficacy - Death from any cause at any time between Day 0 and 96 weeks of follow-up, or the occurrence of confirmed or probable active TB or confirmed active MDR-TB at any time between Day 0 and the week 96 study visit. Safety - Occurrence of a Grade 3 or higher adverse event during the period receiving randomized study drug (DLM or INH). If a HHC has a Grade 3 or 4 event prior to starting randomized study drug, then the same event will only be considered during follow-up if the grade worsens. | — |
Countries
Kenya
Contacts
Public ContactLara Hosey
Clinical Trials Specialist
Outcome results
None listed