Protecting Households On Exposure to Newly Diagnosed Index Multidrug-Resistant Tuberculosis Patients (PHOENIx MDR-TB)
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|ClinicalTrials.gov Identifier: NCT03568383|
Recruitment Status : Recruiting
First Posted : June 25, 2018
Last Update Posted : November 25, 2019
|Condition or disease||Intervention/treatment||Phase|
|Tuberculosis, MDR||Drug: Delamanid (DLM) Drug: Isoniazid (INH) Dietary Supplement: Pyridoxine (vitamin B6)||Phase 3|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||5610 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Protecting Households On Exposure to Newly Diagnosed Index Multidrug-Resistant Tuberculosis Patients (PHOENIx MDR-TB)|
|Actual Study Start Date :||June 3, 2019|
|Estimated Primary Completion Date :||June 18, 2025|
|Estimated Study Completion Date :||June 18, 2025|
Experimental: Arm A: Delamanid (DLM)
HHCs will receive delamanid (DLM) for 26 weeks.
Drug: Delamanid (DLM)
Adults and children ≥30 kg: delamanid 200 mg orally once daily.
Children ≥2.5 kg to <30 kg: weight-band dosing orally once daily as per the study protocol. As children gain weight, their DLM dose should be adjusted, typically every month or as the visit schedule permits.
Experimental: Arm B: Isoniazid (INH)
HHCs will receive isoniazid (INH) and pyridoxine (vitamin B6) for 26 weeks.
Drug: Isoniazid (INH)
Adults and children ≥24 kg: INH 300 mg orally once daily.
Children ≥2.5 kg to <24 kg: INH weight-band dosing orally once daily as per the study protocol. As children gain weight, their INH dose should be adjusted.
Dietary Supplement: Pyridoxine (vitamin B6)
All HHCs in Arm B must receive pyridoxine (vitamin B6) with each dose of INH based on the current local dosing guidelines. For children up to 3 years of age and nursing women, pyridoxine will be given as per local standard of care. Pyridoxine is not supplied through the study.
- Percent of participants with confirmed or probable active TB at any time between Day 0 and the week 96 study visit [ Time Frame: Measured through Week 96 ]TB diagnoses will be reviewed by the independent outcomes review committee to assess whether the HHC had TB, if it was confirmed or probable TB, and if it was MDR-TB.
- Percent of participants who permanently discontinue randomized study drug (DLM or INH) due to a treatment-related adverse event [ Time Frame: Measured through Week 96 ]Requiring discontinuation as defined in the protocol, or in the opinion of the site investigator is a treatment-limiting adverse event.
- Percent of participants with confirmed active MDR-TB at any time between Day 0 and the week 96 study visit [ Time Frame: Measured through Week 96 ]
- Percent of participants who died from any cause at any time between Day 0 and 96 weeks of follow-up [ Time Frame: Measured through Week 96 ]Deaths will be reviewed by the independent outcomes review committee to assess whether the HHC had TB at the time of death, possibly undiagnosed, and relatedness of the death to TB.
- Percent of participants who died from any cause at any time between Day 0 and 96 weeks of follow-up, or with confirmed or probable active TB at any time between Day 0 and the week 96 study visit [ Time Frame: Measured through Week 96 ]Deaths and TB diagnoses will be reviewed by the independent outcomes review committee to assess whether the HHC had TB at the time of death, possibly undiagnosed, and relatedness of the death to TB; and whether the HHC had TB, if it was confirmed or probable TB, and if it was MDR-TB.
- Percent of participants with a Grade 3 or higher adverse event during the period receiving randomized study drug (DLM or INH) [ Time Frame: Measured through Week 26 ]If a HHC has a Grade 3 or higher adverse event prior to starting randomized study drug, then the same event will only be considered during follow-up if the grade worsens.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03568383
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