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Protecting Households On Exposure to Newly Diagnosed Index Multidrug-Resistant Tuberculosis Patients (PHOENIx MDR-TB)

Primary Purpose

Tuberculosis, MDR

Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Delamanid (DLM)
Isoniazid (INH)
Pyridoxine (vitamin B6)
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Tuberculosis, MDR focused on measuring Tuberculosis, Multidrug Resistance, Prevention, Household Contact

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

INDEX CASE

  • Men and women age greater than or equal to 18 years.
  • Pulmonary MDR-TB defined as:

    • Confirmation of rifampin/rifampicin (RIF) resistance and INH resistance by
    • adequate source documentation (including date of testing, test methodology, and test results) of RIF and INH resistance from a licensed/nationally approved* referral program, OR
    • if either or both results are unknown or not adequately documented (as noted above), then confirmation must be obtained using a DAIDS-approved laboratory that operates according to Good Clinical Laboratory Practices (GCLP) guidelines and participates in an appropriate external quality assurance (EQA) program.
    • *NOTE: The term "licensed/nationally approved" refers to a laboratory that has been certified or licensed by an oversight body within that country and approved for RIF and/or INH resistance testing.
    • NOTE: Pre-XDR and XDR TB are not exclusionary. See the A5300B/I2003B/PHOENIx MOPS for study-approved molecular and phenotypic methods.
  • 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:

    • All children 0 to less than 5 years old at the time of enrollment, regardless of LTBI or HIV status;
    • Adults, adolescents, and children greater than or equal to 5 years of age who are LTBI test positive (either TST-positive (greater than or equal to 5 mm) or IGRA-positive), and whose HIV status is negative, indeterminate, or unknown, and who are not non-HIV immunosuppressed;
    • NOTE: Both TST and IGRA testing are required for screening unless TST testing is not available due to global shortages or in-country supply challenges, but only one positive test is required for eligibility.
    • Adults, adolescents, and children greater than or equal to 5 years of age who are HIV-infected or are non-HIV immunosuppressed (defined as receiving anti-tumor necrosis factor (TNF) treatment, or being solid organ or hematologic transplant recipients), regardless of LTBI test status.
  • 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.

    • Absolute neutrophil count (ANC) greater than or equal to 750 cells/mm^3
    • Hemoglobin greater than or equal to 7.4 g/dL
    • Platelet count greater than or equal to 50,000/mm^3
    • Creatinine less than or equal to 2 × upper limit of normal (ULN)
    • Potassium level greater than or equal to 3.0 mEq/L
    • Aspartate aminotransferase (AST) (SGOT) and alanine aminotransferase (ALT) (SGPT) less than or equal to 3 × ULN
    • Total bilirubin less than or equal to 2.5 × ULN (Note: if on atazanavir (ATV), total bilirubin greater than 2.5 x ULN is permitted if direct bilirubin less than or equal to 2.5 × ULN)
    • Albumin greater than 3 g/dL
    • NOTE: Participants with results from other laboratory tests that are outside the normal range may be eligible for the study, at the discretion of the site investigator, if not considered to be an obstacle to entry.
  • 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.

    • NOTE: Reproductive potential is defined as:
    • Girls who have reached menarche or
    • Women who have had menses within the past 12 consecutive months and who do not have an FSH greater than 40 IU/L or
    • Women who have had menses within the past 24 consecutive months if an FSH measurement is not available
    • Women who have not undergone surgical sterilization (e.g., hysterectomy, or bilateral oophorectomy, or bilateral salpingectomy).
    • Female participants who are participating in sexual activity that could lead to pregnancy must agree to use one reliable form of contraceptive (i.e., hormonal contraceptive, condoms, IUD, diaphragm with spermicide, or cervical cap with spermicide) while receiving study treatments.
    • NOTE: Female participants who are not of reproductive potential, as defined above, or whose male partner(s) have undergone successful vasectomy with documented azoospermia or have documented azoospermia for any other reason, are eligible without requiring the use of contraceptives. Participant-reported history is acceptable documentation of menopause, hysterectomy, bilateral oophorectomy, or bilateral salpingectomy.
  • 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

  • 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 CONTACTS

  • Current confirmed or probable or possible pulmonary or extrapulmonary TB, based on the following criteria: the current ACTG Diagnosis Appendix 100 for adults and for children of greater than or equal to 15 years of age; or the modified pediatric TB definitions for children less than 15 years of age as described in the A5300B/I2003B/PHOENIx MOPS.
  • 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 greater than or equal to Grade 2 within 90 days prior to study entry according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017.
  • 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, including but not limited to heart failure, coronary heart disease, second or third degree atrioventricular (AV) block, prolongation of the QRS complex over 120 ms (in both male and female participants), arrhythmia, or tachyarrhythmia.
  • 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. Please see the study protocol for a list of prohibited medications.
  • 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 (e.g., seasonal or migrant workers or students who may not stay in the area).

Sites / Locations

  • Gaborone CRSRecruiting
  • Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRSRecruiting
  • GHESKIO Institute of Infectious Diseases and Reproductive Health (GHESKIO - IMIS) CRSRecruiting
  • Les Centres GHESKIO Clinical Research Site (GHESKIO-INLR) CRSRecruiting
  • Byramjee Jeejeebhoy Medical College (BJMC) CRSRecruiting
  • YRG CARE CRS [Site ID: 32075]
  • Chennai Antiviral Research and Treatment (CART) CRS
  • Moi University Clinical Research Center (MUCRC) CRSRecruiting
  • Socios En Salud Sucursal Perú CRSRecruiting
  • Barranco CRSRecruiting
  • San Miguel CRSRecruiting
  • De La Salle Health Science Institute Angelo King Medical Research Center (DLSHSI-AKMRC)Recruiting
  • Soweto ACTG CRSRecruiting
  • Wits Helen Joseph Hospital CRS (Wits HJH CRS)Recruiting
  • Durban International Clinical Research Site CRSRecruiting
  • PHRU Matlosana CRSRecruiting
  • Rustenburg CRSRecruiting
  • Task Applied Science (TASK) CRS
  • University of Cape Town Lung Institute (UCTLI) CRSRecruiting
  • South African Tuberculosis Vaccine Initiative (SATVI) CRSRecruiting
  • Desmond Tutu TB Centre - Stellenbosch University (DTTC-SU) CRS
  • CAPRISA eThekwini CRSRecruiting
  • Kilimanjaro Christian Medical Centre (KCMC)Recruiting
  • Siriraj Hospital ,Mahidol University NICHD CRSRecruiting
  • Thai Red Cross AIDS Research Centre (TRC-ARC) CRSRecruiting
  • Chiangrai Prachanukroh Hospital NICHD CRSRecruiting
  • Joint Clinical Research Centre (JCRC)/Kampala Clinical Research SiteRecruiting
  • MU-JHU Research Collaboration (MUJHU CARE LTD) CRSRecruiting
  • National Lung Hospital CRS (Site ID: 32483)Recruiting
  • Milton Park CRSRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm A: Delamanid (DLM)

Arm B: Isoniazid (INH)

Arm Description

HHCs will receive delamanid (DLM) for 26 weeks.

HHCs will receive isoniazid (INH) and pyridoxine (vitamin B6) for 26 weeks.

Outcomes

Primary Outcome Measures

Percent of participants with confirmed or probable active TB at any time between Day 0 and the week 96 study visit
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
Requiring discontinuation as defined in the protocol, or in the opinion of the site investigator is a treatment-limiting adverse event.

Secondary Outcome Measures

Percent of participants with confirmed active MDR-TB at any time between Day 0 and the week 96 study visit
Percent of participants with confirmed active MDR-TB at any time between Day 0 and the week 96 study visit
Percent of participants who died from any cause at any time between Day 0 and 96 weeks of follow-up
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
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)
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.

Full Information

First Posted
June 14, 2018
Last Updated
October 6, 2023
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Otsuka Pharmaceutical Development & Commercialization, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03568383
Brief Title
Protecting Households On Exposure to Newly Diagnosed Index Multidrug-Resistant Tuberculosis Patients
Acronym
PHOENIx MDR-TB
Official Title
Protecting Households On Exposure to Newly Diagnosed Index Multidrug-Resistant Tuberculosis Patients (PHOENIx MDR-TB)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 3, 2019 (Actual)
Primary Completion Date
September 30, 2026 (Anticipated)
Study Completion Date
September 30, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Otsuka Pharmaceutical Development & Commercialization, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tuberculosis, MDR
Keywords
Tuberculosis, Multidrug Resistance, Prevention, Household Contact

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
5610 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm A: Delamanid (DLM)
Arm Type
Experimental
Arm Description
HHCs will receive delamanid (DLM) for 26 weeks.
Arm Title
Arm B: Isoniazid (INH)
Arm Type
Experimental
Arm Description
HHCs will receive isoniazid (INH) and pyridoxine (vitamin B6) for 26 weeks.
Intervention Type
Drug
Intervention Name(s)
Delamanid (DLM)
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Isoniazid (INH)
Intervention Description
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.
Intervention Type
Dietary Supplement
Intervention Name(s)
Pyridoxine (vitamin B6)
Intervention Description
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.
Primary Outcome Measure Information:
Title
Percent of participants with confirmed or probable active TB at any time between Day 0 and the week 96 study visit
Description
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.
Time Frame
Measured through Week 96
Title
Percent of participants who permanently discontinue randomized study drug (DLM or INH) due to a treatment-related adverse event
Description
Requiring discontinuation as defined in the protocol, or in the opinion of the site investigator is a treatment-limiting adverse event.
Time Frame
Measured through Week 96
Secondary Outcome Measure Information:
Title
Percent of participants with confirmed active MDR-TB at any time between Day 0 and the week 96 study visit
Description
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
Title
Percent of participants who died from any cause at any time between Day 0 and 96 weeks of follow-up
Description
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.
Time Frame
Measured through Week 96
Title
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
Description
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.
Time Frame
Measured through Week 96
Title
Percent of participants with a Grade 3 or higher adverse event during the period receiving randomized study drug (DLM or INH)
Description
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.
Time Frame
Measured through Week 26

10. Eligibility

Sex
All
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: INDEX CASE Men and women age greater than or equal to 18 years. Pulmonary MDR-TB defined as: Confirmation of rifampin/rifampicin (RIF) resistance and INH resistance by adequate source documentation (including date of testing, test methodology, and test results) of RIF and INH resistance from a licensed/nationally approved* referral program, OR if either or both results are unknown or not adequately documented (as noted above), then confirmation must be obtained using a DAIDS-approved laboratory that operates according to Good Clinical Laboratory Practices (GCLP) guidelines and participates in an appropriate external quality assurance (EQA) program. *NOTE: The term "licensed/nationally approved" refers to a laboratory that has been certified or licensed by an oversight body within that country and approved for RIF and/or INH resistance testing. NOTE: Pre-XDR and XDR TB are not exclusionary. See the A5300B/I2003B/PHOENIx MOPS for study-approved molecular and phenotypic methods. 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: All children 0 to less than 5 years old at the time of enrollment, regardless of LTBI or HIV status; Adults, adolescents, and children greater than or equal to 5 years of age who are LTBI test positive (either TST-positive (greater than or equal to 5 mm) or IGRA-positive), and whose HIV status is negative, indeterminate, or unknown, and who are not non-HIV immunosuppressed; NOTE: Both TST and IGRA testing are required for screening unless TST testing is not available due to global shortages or in-country supply challenges, but only one positive test is required for eligibility. Adults, adolescents, and children greater than or equal to 5 years of age who are HIV-infected or are non-HIV immunosuppressed (defined as receiving anti-tumor necrosis factor (TNF) treatment, or being solid organ or hematologic transplant recipients), regardless of LTBI test status. 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. Absolute neutrophil count (ANC) greater than or equal to 750 cells/mm^3 Hemoglobin greater than or equal to 7.4 g/dL Platelet count greater than or equal to 50,000/mm^3 Creatinine less than or equal to 2 × upper limit of normal (ULN) Potassium level greater than or equal to 3.0 mEq/L Aspartate aminotransferase (AST) (SGOT) and alanine aminotransferase (ALT) (SGPT) less than or equal to 3 × ULN Total bilirubin less than or equal to 2.5 × ULN (Note: if on atazanavir (ATV), total bilirubin greater than 2.5 x ULN is permitted if direct bilirubin less than or equal to 2.5 × ULN) Albumin greater than 3 g/dL NOTE: Participants with results from other laboratory tests that are outside the normal range may be eligible for the study, at the discretion of the site investigator, if not considered to be an obstacle to entry. 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. NOTE: Reproductive potential is defined as: Girls who have reached menarche or Women who have had menses within the past 12 consecutive months and who do not have an FSH greater than 40 IU/L or Women who have had menses within the past 24 consecutive months if an FSH measurement is not available Women who have not undergone surgical sterilization (e.g., hysterectomy, or bilateral oophorectomy, or bilateral salpingectomy). Female participants who are participating in sexual activity that could lead to pregnancy must agree to use one reliable form of contraceptive (i.e., hormonal contraceptive, condoms, IUD, diaphragm with spermicide, or cervical cap with spermicide) while receiving study treatments. NOTE: Female participants who are not of reproductive potential, as defined above, or whose male partner(s) have undergone successful vasectomy with documented azoospermia or have documented azoospermia for any other reason, are eligible without requiring the use of contraceptives. Participant-reported history is acceptable documentation of menopause, hysterectomy, bilateral oophorectomy, or bilateral salpingectomy. 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 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 CONTACTS Current confirmed or probable or possible pulmonary or extrapulmonary TB, based on the following criteria: the current ACTG Diagnosis Appendix 100 for adults and for children of greater than or equal to 15 years of age; or the modified pediatric TB definitions for children less than 15 years of age as described in the A5300B/I2003B/PHOENIx MOPS. 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 greater than or equal to Grade 2 within 90 days prior to study entry according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017. 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, including but not limited to heart failure, coronary heart disease, second or third degree atrioventricular (AV) block, prolongation of the QRS complex over 120 ms (in both male and female participants), arrhythmia, or tachyarrhythmia. 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. Please see the study protocol for a list of prohibited medications. 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 (e.g., seasonal or migrant workers or students who may not stay in the area).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gavin Churchyard, MBBCh MMed FRCP FCP(SA) PhD
Organizational Affiliation
Aurum Institute
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Amita Gupta, MD, MHS
Organizational Affiliation
Johns Hopkins Medical Institutions, Center for Clinical Global Health Education
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Anneke Hesseling, MD, PhD
Organizational Affiliation
University of Stellenbosch
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Susan Swindells, MBBS
Organizational Affiliation
University of Nebraska
Official's Role
Study Chair
Facility Information:
Facility Name
Gaborone CRS
City
Gaborone
State/Province
South-East District
Country
Botswana
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tebogo J. Kakhu
Phone
267-3931353
Email
tkakhu@bhp.org.bw
Facility Name
Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS
City
Rio de Janeiro
ZIP/Postal Code
21040-360
Country
Brazil
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sandra W. Cardoso, Ph.D., M.D.
Phone
55-21-22707064
Email
sandra.wagner@ipec.fiocruz.br
Facility Name
GHESKIO Institute of Infectious Diseases and Reproductive Health (GHESKIO - IMIS) CRS
City
Port-au-Prince
ZIP/Postal Code
HT-6110
Country
Haiti
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yvetot Joseph, M.D.
Phone
509-36832867
Email
yvetotjoseph@gheskio.org
Facility Name
Les Centres GHESKIO Clinical Research Site (GHESKIO-INLR) CRS
City
Port-au-Prince
ZIP/Postal Code
HT-6110
Country
Haiti
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cynthia Riviere, M.D.
Phone
509-22222241
Email
criviere@gheskio.org
Facility Name
Byramjee Jeejeebhoy Medical College (BJMC) CRS
City
Pune
State/Province
Maharashtra
ZIP/Postal Code
411001
Country
India
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nishi Suryavanshi, Ph.D.
Phone
91-98-23248979
Email
nishi@jhumitpune.com
Facility Name
YRG CARE CRS [Site ID: 32075]
City
Chennai
State/Province
Tamil Nadu
ZIP/Postal Code
600010
Country
India
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rifa Khan
Phone
91-967-7290111
Email
rifa@yrgcare.org
Facility Name
Chennai Antiviral Research and Treatment (CART) CRS
City
Chennai
State/Province
Tamil Nadu
ZIP/Postal Code
600113
Country
India
Individual Site Status
Withdrawn
Facility Name
Moi University Clinical Research Center (MUCRC) CRS
City
Eldoret
State/Province
Rift Valley
ZIP/Postal Code
30100
Country
Kenya
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Priscilla C. Cheruiyot
Phone
254-532060850
Email
pcchepkorir@yahoo.com
Facility Name
Socios En Salud Sucursal Perú CRS
City
Lima
ZIP/Postal Code
15001
Country
Peru
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bruno Martel
Phone
51-1-945230659
Email
bmartel_ses@pih.org
Facility Name
Barranco CRS
City
Lima
ZIP/Postal Code
15063
Country
Peru
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Luis A. Limo, D.D.S., MPH
Phone
51-1-2067800
Ext
210
Email
llimo@impactaperu.org
Facility Name
San Miguel CRS
City
Lima
ZIP/Postal Code
32-15088
Country
Peru
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Milagros L. Sabaduche, RGN
Phone
51-1-5521600
Ext
644
Email
msabaduche@impactaperu.org
Facility Name
De La Salle Health Science Institute Angelo King Medical Research Center (DLSHSI-AKMRC)
City
Cavite
ZIP/Postal Code
4114
Country
Philippines
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Maricelle S. Gler
Phone
63-9178230431
Email
tarcelasg@yahoo.com
Facility Name
Soweto ACTG CRS
City
Johannesburg
State/Province
Gauteng
ZIP/Postal Code
1862
Country
South Africa
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Debra Peters
Phone
27-119899700
Email
petersd@phru.co.za
Facility Name
Wits Helen Joseph Hospital CRS (Wits HJH CRS)
City
Johannesburg
State/Province
Gauteng
ZIP/Postal Code
2092
Country
South Africa
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anne Reyneke
Phone
27-11-2768817
Email
areyneke@witshealth.co.za
Facility Name
Durban International Clinical Research Site CRS
City
Durban
State/Province
Kwa Zulu Natal
ZIP/Postal Code
4052
Country
South Africa
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rosie Mngqibisa, MB ChB, M.B.B.S.
Phone
27-31-2611093
Email
mngqibisa@ecarefoundation.com
Facility Name
PHRU Matlosana CRS
City
Klerksdorp
State/Province
North West Province
ZIP/Postal Code
2574
Country
South Africa
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tumelo Moloantoa, MD
Phone
27-18-4653751
Email
moloantoat@phru.co.za
Facility Name
Rustenburg CRS
City
Rustenburg
State/Province
North West Province
ZIP/Postal Code
0300
Country
South Africa
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tania Adonis
Phone
27-87-1351587
Email
tadonis@auruminstitute.org
Facility Name
Task Applied Science (TASK) CRS
City
Cape Town
State/Province
Western Cape Province
ZIP/Postal Code
7530
Country
South Africa
Individual Site Status
Completed
Facility Name
University of Cape Town Lung Institute (UCTLI) CRS
City
Cape Town
State/Province
Western Cape Province
ZIP/Postal Code
7700
Country
South Africa
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Catrien Drinkwater
Phone
27-21-4066850
Email
catrien.drinkwater@uct.ac.za
Facility Name
South African Tuberculosis Vaccine Initiative (SATVI) CRS
City
Cape Town
State/Province
Western Cape Province
ZIP/Postal Code
7705
Country
South Africa
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chris Hikuam
Phone
27-21-4066228
Email
chris.hikuam@uct.ac.za
Facility Name
Desmond Tutu TB Centre - Stellenbosch University (DTTC-SU) CRS
City
Cape Town
State/Province
Western Cape
ZIP/Postal Code
7505
Country
South Africa
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Frieda A Verheye-Dua
Phone
27-21-9389772
Email
Frieda@sun.ac.za
Facility Name
CAPRISA eThekwini CRS
City
Durban
ZIP/Postal Code
4001
Country
South Africa
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bongekile Zuma
Phone
27-31-6550658
Email
Bongi.Zuma@caprisa.org
Facility Name
Kilimanjaro Christian Medical Centre (KCMC)
City
Moshi
Country
Tanzania
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Boniface N. Njau, B.S., M.S.
Phone
255-75-4933559
Email
bnneneu@yahoo.com
Facility Name
Siriraj Hospital ,Mahidol University NICHD CRS
City
Bangkok
State/Province
Bangkoknoi
ZIP/Postal Code
10700
Country
Thailand
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Watcharee Lermankul
Phone
66-2-4197000
Ext
5695
Email
watchareeped@gmail.com
Facility Name
Thai Red Cross AIDS Research Centre (TRC-ARC) CRS
City
Pathum Wan
State/Province
Bangkok
ZIP/Postal Code
10330
Country
Thailand
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Parawee Thongpaeng
Phone
662-6523040
Ext
106
Email
parawee.t@hivnat.org
Facility Name
Chiangrai Prachanukroh Hospital NICHD CRS
City
Chiang Mai
ZIP/Postal Code
50100
Country
Thailand
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pra-ornsuda Sukrakanchana
Phone
66-81-7468858
Email
Pra-ornsuda.Sukrakanchana@phpt.org
Facility Name
Joint Clinical Research Centre (JCRC)/Kampala Clinical Research Site
City
Kampala
Country
Uganda
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sandra Rwambuya, M.P.H.
Phone
256-772-779283
Email
dxr23@case.edu
Facility Name
MU-JHU Research Collaboration (MUJHU CARE LTD) CRS
City
Kampala
Country
Uganda
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Carolyne P. Onyango, MB ChB, M.S.
Phone
256-414-541044
Email
carolonyango@mujhu.org
Facility Name
National Lung Hospital CRS (Site ID: 32483)
City
Vĩnh Phúc
State/Province
Hanoi
ZIP/Postal Code
100000
Country
Vietnam
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tran V Viet Ha
Phone
84-912-785886
Email
vietha@live.unc.edu
Facility Name
Milton Park CRS
City
Milton Park
State/Province
Harare
Country
Zimbabwe
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rachel Mahachi, M.Sc., R.N.
Phone
263-24-2701356
Email
rmahachi@uzchs-ctrc.org

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Individual participant data that underlie results in the publication, after deidentification.
IPD Sharing Time Frame
Beginning 3 months following publication and available throughout period of funding of the AIDS Clinical Trials Group by NIH.
IPD Sharing Access Criteria
With whom? Researchers who provide a methodologically sound proposal for use of the data that is approved by the AIDS Clinical Trials Group. For what types of analyses? To achieve aims in the proposal approved by the AIDS Clinical Trials Group. By what mechanism will data be made available? Researchers may submit a request for access to data using the AIDS Clinical Trials Group "Data Request" form at: https://actgnetwork.org/about-actg/templates-and-forms. Researchers of approved proposals will need to sign an AIDS Clinical Trials Group Data Use Agreement before receiving the data.

Learn more about this trial

Protecting Households On Exposure to Newly Diagnosed Index Multidrug-Resistant Tuberculosis Patients

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