Perinatal HIV Research Unit (PHRU) | Soweto ACTG CRS
Status and phase
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About
The purpose of this study is to compare the efficacy and safety of 26 weeks of delamanid (DLM) versus 26 weeks of isoniazid (INH) for preventing confirmed or probable active tuberculosis (TB) during 96 weeks of follow-up among high-risk household contacts (HHCs) of adults with multidrug-resistant tuberculosis (MDR-TB) (index cases). High-risk HHCs are those with HIV or non-HIV immunosuppression, latent TB infection, and young children below the age of 5 years.
Full description
This study will compare the efficacy and safety of 26 weeks of delamanid (DLM) versus 26 weeks of isoniazid (INH) for preventing confirmed or probable active tuberculosis (TB) during 96 weeks of follow-up among high-risk household contacts (HHCs) of adults with multidrug-resistant tuberculosis (MDR-TB) (index cases). High-risk HHCs are those with HIV or non-HIV immunosuppression, latent TB infection, and young children below the age of 5 years.
If at least one HHC within a household (HH) is found to be eligible, the HH will be randomized to one of the following:
Arm A: DLM daily for adults, adolescents, and children, given for 26 weeks.
Arm B: INH daily for adults, adolescents, and children, given for 26 weeks AND pyridoxine (vitamin B6) daily for adults, adolescents, and children, given for 26 weeks.
All high-risk HHCs in the same HH will receive the same randomized regimen.
All participants will be in the study for 96 weeks. At study entry, index cases will undergo a medical history review and sputum collection. HHCs will have study visits at study entry and at Weeks 2, 4, 8, 12, 16, 20, 26, 36, 48, 60, 72, 84, and 96. Visits may include physical examinations; blood, urine, and sputum collection; electrocardiograms (ECGs); and questionnaires and assessments. Forty HHCs under the age of 5 taking DLM will undergo an intensive PK visit at Week 8.
Enrollment
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Volunteers
Inclusion criteria
INDEX CASE
Men and women age greater than or equal to 18 years.
Pulmonary MDR-TB defined as:
Started MDR-TB treatment within the past 90 days.
Ability and willingness of the index case to provide informed consent to access the HH and approach HH members for evaluation.
HH of index case has at least one reported HHC.
HOUSEHOLD CONTACTS
If any member(s) of the HH is/are not eligible or do not want to participate, all other eligible TB contacts within the HH can still participate.
Currently lives or lived in the same dwelling unit or plot of land and shares or has shared the same housekeeping arrangements as the index case and who reports exposure within 90 days prior to the index case starting MDR-TB treatment. Also, shared greater than 4 hours of indoor airspace with the index case during any one-week period prior to the index case starting MDR-TB treatment.
HHCs must be in one of the following high-risk groups:
HIV-1 infection status must be documented as positive, negative, indeterminate or unknown for all HHCs. Unknown status includes those who previously tested HIV negative but the test was performed more than one year ago. HIV testing will be offered to all HHCs with negative of unknown status. For adults (18 years and older), HIV-1 infection must be documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen or plasma HIV-1 RNA viral load greater than 1000 copies/mL. Two or more plasma HIV-1 RNA viral loads of greater than 1,000 copies/mL are also acceptable as documentation of HIV infection. More information is available on this criterion in the protocol.
The following specific laboratory values for infants, children, and adults obtained within 30 days prior to study entry by any DAIDS-approved non-US laboratory.
For females of reproductive potential, negative serum or urine pregnancy test within 7 days prior to study entry by any DAIDS-approved non-US laboratory that operates in accordance with GCLP and participates in appropriate external quality assurance programs.
For infants (0 to 1 year of age), weight greater than or equal to 2.5 kg at screening.
Ability and willingness of participant or legally-authorized representative (legal guardian or biological parent) to provide informed consent or assent as appropriate.
Chest radiograph without evidence of active TB performed within 70 days prior to study entry for HHCs greater than or equal to 2 years of age and within 30 days prior to study entry for HHCs less than 2 years of age.
QTcF interval less than or equal to 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. In the event that a HHC is suspected of having TB, then this window for enrollment may be extended from within 30 days to within 70 days to allow for TB testing of the HHC.
Exclusion criteria
INDEX CASE
HOUSEHOLD CONTACTS
Primary purpose
Allocation
Interventional model
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5,610 participants in 2 patient groups
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Data sourced from clinicaltrials.gov
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