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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
AIDS Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT01380080
First received: June 22, 2011
Last updated: February 29, 2016
Last verified: February 2016
Results First Received: January 26, 2016  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: HIV Infection
Interventions: Drug: Atripla (r)
Drug: Efavirenz
Drug: Truvada
Drug: Rifampin/isoniazid/pyrazinamide/ethambutol FDC
Drug: Rifampin/isoniazid FDC
Drug: Isoniazid

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Recruited at AIDS Clinical Trials Units in 10 international countries. Recruitment occurred between October 31, 2011 (date of first participant was randomized) and June 9, 2014 (date of last participant was randomized).

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
851 were randomized 1:1 to treatment strategies A and B. Results reported for 850 eligible participants; 1 was subsequently found ineligible and excluded from all analyses.

Reporting Groups
  Description
Arm A: Empiric 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/isoniazid/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/isoniazid). All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only
Arm B: IPT 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. Pyridoxine is provided by the sites to all participants while they are receiving isoniazid (INH).

Participant Flow:   Overall Study
    Arm A: Empiric   Arm B: IPT
STARTED   424   426 
COMPLETED   391   403 
NOT COMPLETED   33   23 
Death                20                22 
Withdrawal by Subject                4                0 
Not able to get to clinic                4                0 
Not willing to adhere to requirements                3                1 
Lost to Follow-up                2                0 



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent to treat: All eligible participants were included in the baseline characteristics.

Reporting Groups
  Description
Arm A: Empiric 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/isoniazid/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/isoniazid). All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only
Arm B: IPT 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. Pyridoxine is provided by the sites to all participants while they are receiving isoniazid (INH).
Total Total of all reporting groups

Baseline Measures
   Arm A: Empiric   Arm B: IPT   Total 
Overall Participants Analyzed 
[Units: Participants]
 424   426   850 
Age 
[Units: Years]
Median (Inter-Quartile Range)
 36 
 (30 to 42) 
 35 
 (30 to 42) 
 36 
 (30 to 42) 
Gender 
[Units: Participants]
     
Female   200   200   400 
Male   224   226   450 
Race/Ethnicity, Customized 
[Units: Participants]
     
Black Non-Hispanic   375   384   759 
Hispanic (Regardless of Race)   32   29   61 
Asian, Pacific Islander   17   13   30 
Region of Enrollment 
[Units: Participants]
     
Haiti   53   56   109 
Malawi   95   98   193 
Brazil   9   6   15 
South Africa   86   90   176 
Zimbabwe   25   27   52 
Uganda   25   24   49 
Zambia   17   19   36 
Kenya   77   75   152 
Peru   20   19   39 
India   17   12   29 
HIV-1 RNA 
[Units: Log10 copies/mL]
Median (Inter-Quartile Range)
 5.4 
 (5.0 to 5.7) 
 5.3 
 (4.9 to 5.7) 
 5.3 
 (4.9 to 5.7) 
CD4+ T-cell count 
[Units: Cells/mm^3]
Median (Inter-Quartile Range)
 18 
 (9 to 31) 
 19 
 (9 to 33) 
 18 
 (9 to 32) 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Cumulative Probability of Death or Unknown Vital Status by Week 24   [ Time Frame: From study entry to week 24 ]

2.  Secondary:   Cumulative Probability of Death by Week 24   [ Time Frame: From study entry to week 24 ]

3.  Secondary:   Cumulative Probability of Death or AIDS Progression by Week 24   [ Time Frame: From study entry to week 24 ]

4.  Secondary:   Proportion of Participants With HIV-1 RNA Level <400 Copies/mL   [ Time Frame: At weeks 0, 4, 24, and 48 ]

5.  Secondary:   CD4+ T-cell Count   [ Time Frame: At weeks 0, 4, 24, and 48 ]

6.  Secondary:   CD4+ T-cell Count Change From Baseline   [ Time Frame: From study entry to weeks 4, 24 and 48 ]

7.  Secondary:   Cumulative Probability of First AIDS Progression by Week 96   [ Time Frame: From study entry to week 96 ]
Results not yet reported.   Anticipated Reporting Date:   12/2020   Safety Issue:   Yes

8.  Secondary:   Time to Initiation of TB Treatment by Week 96   [ Time Frame: From study entry to week 96 ]
Results not yet reported.   Anticipated Reporting Date:   12/2020   Safety Issue:   No

9.  Secondary:   Proportion of Participants With TB Diagnosis Per Current ACTG Diagnosis Appendix by Week 96   [ Time Frame: From study entry to week 96 ]
Results not yet reported.   Anticipated Reporting Date:   12/2020   Safety Issue:   Yes

10.  Secondary:   Proportion of Participants With at Least One New Grade 3 or 4 Adverse Event That is at Least a One-grade Increase From Baseline by Week 48   [ Time Frame: From study entry to week 48 ]
Results not yet reported.   Anticipated Reporting Date:   12/2020   Safety Issue:   Yes

11.  Secondary:   Proportion of Participants With at Least One New Grade 3 or 4 That is at Least a One-grade Increase From Baseline for the Following Targeted Laboratory Values by Week 48   [ Time Frame: From study entry to week 48 ]
Results not yet reported.   Anticipated Reporting Date:   12/2020   Safety Issue:   Yes

12.  Secondary:   Proportion of Participants With IRIS (Using Current ACTG Definition) by Week 48   [ Time Frame: From study entry to week 48 ]
Results not yet reported.   Anticipated Reporting Date:   12/2020   Safety Issue:   Yes

13.  Secondary:   Proportion of Participants With Reportable Hospitalization by Week 48   [ Time Frame: From study entry to week 48 ]
Results not yet reported.   Anticipated Reporting Date:   12/2020   Safety Issue:   Yes

14.  Secondary:   Proportion of Participants Who Prematurely Discontinued Any Component of TB Treatment by Week 48   [ Time Frame: From study entry to week 48 ]
Results not yet reported.   Anticipated Reporting Date:   12/2020   Safety Issue:   No

15.  Secondary:   Proportion of Participants Who Prematurely Discontinued Antiretroviral Therapy by Week 48   [ Time Frame: From study entry to week 48 ]
Results not yet reported.   Anticipated Reporting Date:   12/2020   Safety Issue:   No


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: ACTG Clinicaltrials.gov Coordinator
Organization: ACTG Network Coordinating Center, Social & Scientific Systems, Inc.
phone: (301) 628-3313
e-mail: ACTGCT.Gov@s-3.com


Publications:
M. Hosseinipour, G. Bisson, S., et al. Empiric TB therapy does not decrease early mortality compared to Isoniazid Preventive therapy in adults with advanced HIV initiating ART: Results of ACTG A5274 (REMEMBER study). Program and abstracts of the 8th IAS Conference on HIV Pathogenesis, Treatment and prevention; July 19-22, 2015; Vancouver, Canada. Abstract A-729-0105-03495
Johnstone Kumwenda, Amita Gupta, et al. Empiric TB therapy versus IPT in HIV-infected persons initiating ART (ACTG A5274 48 week results). Program and abstracts of the 2016 Conference on Retroviruses and Opportunistic Infections; February 22-25, 2016; Boston, Massachusetts. Abstract 16-1383
Gregory P. Bisson, Amita Gupta, et al. Urine LAM Testing in Advanced HIV-Infected Adults in a Trial of Empiric TB Therapy. Program and abstracts of the 2016 Conference on Retroviruses and Opportunistic Infections; February 22-25, 2016; Boston, Massachusetts. Abstract 16-1650

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: AIDS Clinical Trials Group
ClinicalTrials.gov Identifier: NCT01380080     History of Changes
Other Study ID Numbers: ACTG A5274
1U01AI068636 ( US NIH Grant/Contract Award Number )
Study First Received: June 22, 2011
Results First Received: January 26, 2016
Last Updated: February 29, 2016
Health Authority: United States: Federal Government