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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
AIDS Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT01380080
First received: June 22, 2011
Last updated: May 19, 2015
Last verified: May 2015
  Purpose

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.


Condition Intervention Phase
HIV Infection
Drug: Atripla (r)
Drug: Efavirenz
Drug: Truvada
Drug: Rifampin/isoniazid/pyrazinamide/ethambutol FDC
Drug: Rifampin/isoniazid FDC
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Reducing Early Mortality and Early Morbidity by Empiric Tuberculosis Treatment Regimens (REMEMBER)

Resource links provided by NLM:


Further study details as provided by AIDS Clinical Trials Group:

Primary Outcome Measures:
  • Survival status at 24 weeks post randomization [ Time Frame: Randomization to 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 851
Study Start Date: October 2011
Estimated Study Completion Date: April 2016
Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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 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
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)

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01380080

Locations
Brazil
Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS
Rio de Janeiro,, Brazil, 21045-900
Haiti
GHESKIO Institute of Infectious Diseases and Reproductive Health (GHESKIO - IMIS) CRS
Port Au Prince, Haiti
Les Centres GHESKIO CRS
Port-au-Prince, Haiti, 6110
India
YRG CARE Medical Ctr., VHS Chennai CRS
Rajiv Gandhi Salai Taramani, Chennai, India, 600113
BJ Medical College CRS
Pune, Maharashtra, India, 411001
Kenya
AMPATH at Moi Univ. Teaching Hosp. Eldoret CRS
Eldoret, Kenya, 30100
Walter Reed Project - Kenya Med. Research Institute Kericho CRS
Kericho, Kenya, 20200
Malawi
College of Med. JHU CRS (30301)
Blantyre, Malawi
University of North Carolina Lilongwe CRS (12001)
Lilongwe, Malawi
Peru
San Miguel CRS
San Miguel, Lima, Peru
Barranco CRS (11301)
Lima, Peru, 18 PE
South Africa
Wits HIV CRS
Johannesburg, Gauteng, South Africa
CAPRISA eThekwini CRS
Durban, KwaZulu-Natal, South Africa, 4011
Durban Adult HIV CRS
Durban, KwaZulu-Natal, South Africa
Soweto ACTG CRS (12301)
Johannesburg, South Africa
Uganda
Joint Clinical Research Centre (JCRC) (12401)
Kampala, Uganda
Zambia
Kalingalinga Clinic CRS (12801)
Lusaka, Zambia
Zimbabwe
UZ-Parirenyatwa CRS
AIDS Research Unit P.O. Box A178, Harare, Zimbabwe
Sponsors and Collaborators
AIDS Clinical Trials Group
Investigators
Study Chair: Mina C Hosseinipour, MD University of North Carolina Lilongwe CRS
Study Chair: Johnstone Kumwenda, MD, MBBS, MMED College of Med. JHU CRS
  More Information

No publications provided

Responsible Party: AIDS Clinical Trials Group
ClinicalTrials.gov Identifier: NCT01380080     History of Changes
Other Study ID Numbers: ACTG A5274, 1U01AI068636
Study First Received: June 22, 2011
Last Updated: May 19, 2015
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Tuberculosis
Actinomycetales Infections
Bacterial Infections
Gram-Positive Bacterial Infections
Mycobacterium Infections
Ethambutol
Isoniazid
Pyrazinamide
Rifampin
Tenofovir
Tenofovir disoproxil
Anti-Bacterial Agents
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antibiotics, Antitubercular
Antimetabolites
Antitubercular Agents
Antiviral Agents
Enzyme Inhibitors
Fatty Acid Synthesis Inhibitors
Hypolipidemic Agents
Leprostatic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on May 28, 2015