REMEMBER: Reducing Early Mortality & Morbidity by Empiric Tuberculosis (TB) Treatment

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by AIDS Clinical Trials Group
Sponsor:
Collaborator:
Information provided by (Responsible Party):
AIDS Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT01380080
First received: June 22, 2011
Last updated: April 29, 2014
Last verified: April 2014

June 22, 2011
April 29, 2014
October 2011
August 2014   (final data collection date for primary outcome measure)
Survival status at 24 weeks post randomization [ Time Frame: Randomization to 24 weeks ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01380080 on ClinicalTrials.gov Archive Site
  • Time from randomization to death [ Time Frame: Randomization to 96 weeks ] [ Designated as safety issue: No ]
  • Time from randomization to AIDS progression (defined as the identification of a new World Health Organization (WHO) stage 3 or 4 condition) [ Time Frame: Randomization to 96 weeks ] [ Designated as safety issue: No ]
  • AIDS-free survival status at 24 and 48 weeks (cumulative) [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • HIV-1 RNA level (<400 vs. ≥400 copies/mL) at weeks 4, 24, and 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Safety and tolerability status at 24 and 48 weeks (cumulative) [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]

    Safety endpoints-

    1. new Grade 3 or 4 laboratory or sign or symptom that is at least a one-grade increase from baseline
    2. new Grade 3 or 4 that is at least a one-grade increase from baseline for the following targeted laboratory values: hemoglobin, serum creatinine, ALT and AST
    3. IRIS (using current ACTG definition)
    4. reportable hospitalization

    Tolerability endpoints-

    1. premature discontinuation of any component of TB treatment
    2. premature discontinuation of antiretroviral therapy (ART)
  • Time to initiation of TB treatment [ Time Frame: Randomization to 96 weeks ] [ Designated as safety issue: No ]
  • CD4+ cell count and change from baseline at weeks 4, 24, and 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • TB diagnosis per current ACTG Diagnosis Appendix [ Time Frame: Randomization to 96 weeks ] [ Designated as safety issue: No ]
  • Time from randomization to death [ Time Frame: Randomization to 96 weeks ] [ Designated as safety issue: No ]
  • Time from randomization to AIDS progression (defined as the identification of a new WHO stage 3 or 4 condition) [ Time Frame: Randomization to 96 weeks ] [ Designated as safety issue: No ]
  • AIDS-free survival status at 24 and 48 weeks (cumulative) [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • HIV-1 RNA level (<400 vs. ≥400 copies/mL) at weeks 4, 24, and 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Safety and tolerability status at 24 and 48 weeks (cumulative) [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]

    Safety endpoints-

    1. new Grade 3 or 4 laboratory or sign or symptom that is at least a one-grade increase from baseline
    2. new Grade 3 or 4 that is at least a one-grade increase from baseline for the following targeted laboratory values: hemoglobin, serum creatinine, ALT and AST
    3. IRIS (using current ACTG definition)
    4. reportable hospitalization

    Tolerability endpoints-

    1. premature discontinuation of any component of TB treatment
    2. premature discontinuation of ART
  • Time to initiation of TB treatment [ Time Frame: Randomization to 96 weeks ] [ Designated as safety issue: No ]
  • CD4+ cell count and change from baseline at weeks 4, 24, and 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • TB diagnosis per current ACTG Diagnosis Appendix [ Time Frame: Randomization to 96 weeks ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
REMEMBER: Reducing Early Mortality & Morbidity by Empiric Tuberculosis (TB) Treatment
Reducing Early Mortality and Early Morbidity by Empiric Tuberculosis Treatment Regimens (REMEMBER)

People with HIV have a high chance of becoming infected with TB, especially when they live in areas where TB infection is common. It can be difficult to diagnose TB in people who need to start HIV treatment right away. Within about 6 months after starting HIV treatment, some of these people can become very sick with TB and can even die from it.

This study is being done in people who are starting HIV treatment and who live in areas where the TB infection rate is high. The purpose of this study is to test an experimental approach to TB treatment to see if it is better than the usual approach. The experimental approach is to start TB treatment at the same time as HIV treatment, even when TB infection has not been found. The usual approach is to start TB treatment only if TB infection is found.

In this study, half of the people will start TB treatment at the same time as they start their HIV treatment. The other half will start TB treatment only if TB infection is found.

The study will also test how safe and effective it is to start TB treatment at about the same time as HIV treatment even when TB infection has not been found. The study will collect information about diet, whether (and when) people in the study become sicker or die, how well their HIV is controlled, how they are feeling, how they are taking their medications, whether it matters where they live or what kind of HIV and TB care is standard, how many people are diagnosed with TB while in the study, and how the cost of the two treatment options on a national level could be compared.

Not Provided
Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
HIV Infection
  • Drug: Atripla (r)
    Patients are administered one tablet of Efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg (EFV/FTC/TDF, Atripla)to taken be taken orally once daily at bedtime without food.
  • Drug: Efavirenz
    Participants will take one 600 mg tablet administered orally once daily without food.
    Other Name: EFV
  • Drug: Truvada
    Participants will take one tablet of Emtricitabine 200mg/tenofovir disoproxil fumarate 300mg (FTC/TDF, Truvada) administered orally once daily with or without food.
  • Drug: Rifampin/isoniazid/pyrazinamide/ethambutol FDC
    Participants will be administered Rifampin/isoniazid/pyrazinamide/ethambutol FDC tablets once daily; dose by weight as determined in Table 5.1-1 of the protocol, for the first 8 weeks. (For Arm B: Local standard of care, FDC tablets will not be administered beyond week 48)
  • Drug: Rifampin/isoniazid FDC
    Participants will be administered rifampin/isoniazid FDC tablets orally, once daily; dose by weight as determined in Table 5.1-1 in the protocol, for 16 weeks following the first 8 weeks. (For Arm B: Local standard of care, FDC tablets will not be administered beyond week 48)
  • Experimental: Arm A: public health approach
    Study treatment for Arm A participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral treatment as soon as possible following randomization and within no more than 3 days following randomization plus a 4-drug anti-tuberculosis treatment (ATT) regimen (defined as rifampin/ethambutol/pyrazinamide) as soon as possible following randomization and within no more than 7 days following initiation of antiretroviral therapy. After 2 months (or 8 weeks), the 4-drug ATT will be followed with 4 months (or 16 weeks) of 2-drug ATT (defined as rifampin/ethambutol). All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only
    Interventions:
    • Drug: Atripla (r)
    • Drug: Efavirenz
    • Drug: Truvada
    • Drug: Rifampin/isoniazid/pyrazinamide/ethambutol FDC
    • Drug: Rifampin/isoniazid FDC
  • Experimental: Arm B: Individualized treatment approach
    Study treatment for Arm B participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral therapy as soon as possible following randomization and within no more than 3 days following randomization and of initiating anti-TB treatment (ATT) only when indicated according to local standard practice and at the discretion of the site investigator. All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only
    Interventions:
    • Drug: Atripla (r)
    • Drug: Efavirenz
    • Drug: Truvada
    • Drug: Rifampin/isoniazid/pyrazinamide/ethambutol FDC
    • Drug: Rifampin/isoniazid FDC
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
836
May 2016
August 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • HIV-1 infection
  • Willingness to start efavirenz-based ART as soon as possible and within no more than 3 days following randomization.
  • CD4+ cell count <50 cells/mm3 obtained within 45 days prior to study entry at any laboratory that has a CLIA certification or its equivalent.
  • Aspartate aminotransferase (AST) (SGOT), alanine aminotransferase (ALT) (SGPT), and total bilirubin ≤ 2.5 X ULN within 30 days prior to study entry.
  • Creatinine clearance ≥30 mL/min either measured or estimated* using values obtained within 30 days prior to study entry.
  • Results from a hepatitis B surface antigen test performed within 30 days prior to study entry.
  • Agreement not to participate in a conception process (e.g., active attempt to become pregnant or to impregnate, donate sperm, in vitro fertilization).
  • Female candidates of reproductive potential must have a negative serum or urine (15-25 mIU/mL) pregnancy test result within 7 days prior to study entry.
  • Female candidates of reproductive potential who are participating in sexual activity that could lead to pregnancy must use two reliable methods of contraception while on study.
  • Karnofsky performance score >/= 30 at time of study entry.
  • Males and females age >/= 13 years.
  • Ability to swallow medications.
  • Ability and willingness of participant or legal guardian/representative to provide informed consent.
  • Intention to remain in the same general geographic region for the duration of study participation.

Exclusion Criteria:

  • Presence of any confirmed or probable TB based on criteria listed in the current ACTG diagnosis appendix within 30 days prior to study entry and following completion of study-specific screening algorithm.
  • Use of single-dose NVP for prevention of mother-to-child transmission (pMTCT) within 24 months prior to study entry.
  • Use of prohibited medications (see list in A5274/REMEMBER MOPS, section 3.2.1) within 30 days prior to study entry.
  • Known allergy/sensitivity or any hypersensitivity to components of study-required ART or TB treatment.
  • Current receipt of treatment for active TB or receipt of >14 days cumulative treatment for active TB within 96 weeks prior to study entry.
  • Receipt of >30 days cumulative of INH prophylaxis within 48 weeks prior to study entry.
  • Receipt at any time prior to study entry of >7 days cumulative treatment with any ARV or combination of ARVs (except for ARVs taken for any length of time during pregnancy for pMTCT, or ARVs taken for occupational exposure).
  • Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
  • Current Grade ≥2 neuropathy.
  • History of multi-drug-resistant (MDR) TB.
  • Within 12 weeks prior to entry, exposure to a household member or co-worker with known MDR TB.
Both
13 Years and older
No
Kenya,   India,   South Africa,   Malawi,   Brazil,   Tanzania,   Haiti,   Peru,   Zimbabwe
 
NCT01380080
ACTG A5274, 1U01AI068636
Yes
AIDS Clinical Trials Group
AIDS Clinical Trials Group
National Institute of Allergy and Infectious Diseases (NIAID)
Study Chair: Mina C Hosseinipour, MD University of North Carolina Lilongwe CRS
Study Chair: Johnstone Kumwenda, MD, MBBS, MMED College of Med. JHU CRS
AIDS Clinical Trials Group
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP