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Comparative Study of Three NNRTI-Sparing HAART Regimens

This study has been completed.
Sponsor:
Collaborators:
National Institute of Allergy and Infectious Diseases (NIAID)
Bristol-Myers Squibb
Gilead Sciences
Merck Sharp & Dohme Corp.
Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
Information provided by (Responsible Party):
AIDS Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00811954
First received: December 18, 2008
Last updated: September 4, 2014
Last verified: September 2014
Results First Received: June 23, 2014  
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: Emtricitabine/tenofovir disoproxil fumarate
Drug: Raltegravir
Drug: Darunavir
Drug: Ritonavir
Drug: Atazanavir

  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 the United States and Puerto Rico. Recruitment occurred between May 22, 2009 (date first subject was randomized) and June 9, 2011 (date last subject was randomized).

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
1814 were randomized 1:1:1 to treatment arms A, B, and C. Results reported for 1809 eligible participants; 5 were subsequently found ineligible and excluded from all analyses.

Reporting Groups
  Description
Arm A: ATV/RTV + FTC/TDF

Emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), ritonavir (RTV), and atazanavir (ATV) to be taken orally, once daily.

Emtricitabine/tenofovir disoproxil fumarate: A combination drug of two nucleoside reverse transcriptase inhibitors (NRTIs) Ritonavir: A protease inhibitor (PI) Atazanavir: A protease inhibitor (PI)

Arm B: RAL + FTC/TDF

FTC/TDF orally, once daily, and raltegravir (RAL) orally, twice daily.

Emtricitabine/tenofovir disoproxil fumarate: A combination drug of two nucleoside reverse transcriptase inhibitors (NRTIs) Raltegravir: An integrase inhibitor (INI)

Arm C: DRV/RTV + FTC/TDF

FTC/TDF, darunavir (DRV), and RTV, orally, once daily.

Emtricitabine/tenofovir disoproxil fumarate: A combination drug of two nucleoside reverse transcriptase inhibitors (NRTIs) Darunavir: A protease inhibitor (PI) Ritonavir: A protease inhibitor (PI)


Participant Flow:   Overall Study
    Arm A: ATV/RTV + FTC/TDF   Arm B: RAL + FTC/TDF   Arm C: DRV/RTV + FTC/TDF
STARTED   605   603   601 
COMPLETED   516   531   500 
NOT COMPLETED   89   72   101 
Death                10                6                13 
Lost to Follow-up                29                23                34 
Not able to get to clinic                28                35                30 
Not willing to adhere to requirements                12                2                16 
Withdraw consent prior study completion                4                6                5 
Site Closure                4                0                1 
Severe Debilitation                2                0                1 
Complete Protocol: No follow-up                0                0                1 



  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.
Intention to treat: All eligible participants were included in the baseline characteristics.

Reporting Groups
  Description
Arm A: ATV/RTV + FTC/TDF

Emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), ritonavir (RTV), and atazanavir (ATV) to be taken orally, once daily.

Emtricitabine/tenofovir disoproxil fumarate: A combination drug of two nucleoside reverse transcriptase inhibitors (NRTIs) Ritonavir: A protease inhibitor (PI) Atazanavir: A protease inhibitor (PI)

Arm B: RAL + FTC/TDF

FTC/TDF orally, once daily, and raltegravir (RAL) orally, twice daily.

Emtricitabine/tenofovir disoproxil fumarate: A combination drug of two nucleoside reverse transcriptase inhibitors (NRTIs) Raltegravir: An integrase inhibitor (INI)

Arm C: DRV/RTV + FTC/TDF

FTC/TDF, darunavir (DRV), and RTV, orally, once daily.

Emtricitabine/tenofovir disoproxil fumarate: A combination drug of two nucleoside reverse transcriptase inhibitors (NRTIs) Darunavir: A protease inhibitor (PI) Ritonavir: A protease inhibitor (PI)

Total Total of all reporting groups

Baseline Measures
   Arm A: ATV/RTV + FTC/TDF   Arm B: RAL + FTC/TDF   Arm C: DRV/RTV + FTC/TDF   Total 
Overall Participants Analyzed 
[Units: Participants]
 605   603   601   1809 
Age 
[Units: Participants]
       
<=18 years   2   2   2   6 
Between 18 and 65 years   597   598   595   1790 
>=65 years   6   3   4   13 
Age 
[Units: Years]
Mean (Standard Deviation)
 38  (11)   37  (11)   38  (11)   37  (11) 
Gender 
[Units: Participants]
       
Female   144   148   143   435 
Male   461   455   458   1374 
Race/Ethnicity, Customized [1] 
[Units: Participants]
       
White Non-Hispanic   212   212   191   615 
Black Non-Hispanic   252   254   251   757 
Hispanic (Regardless of Race)   125   117   148   390 
Asian, Pacific Islander   11   13   6   30 
American Indian, Alaskan Native   2   2   2   6 
More than one race   2   3   2   7 
Unknown/missing   1   2   1   4 
[1] Race/Ethnicity was collected prior to study entry
HIV-1 RNA [1] 
[Units: Log10 copies/mL]
Mean (Standard Deviation)
 4.6  (0.7)   4.6  (0.7)   4.6  (0.7)   4.6  (0.7) 
[1] HIV-1 RNA was calculated as the geometric mean of the two most recent HIV-1 RNA (log 10 copies/mL) obtained on or before study entry. In the event that these two values differed by more than 1log10 copy/mL, the outlying value (based on review of all HIV-1 RNA levels available prior to study entry by the study virologist) was excluded and baseline determined by the remaining sample. Note that screening HIV-1 RNA values were not sued in the calculation of baseline HIV-1 RNA levels.
CD4+ T-cell count [1] 
[Units: Cells/mm^3]
Mean (Standard Deviation)
 309  (189)   306  (199)   310  (189)   308  (192) 
[1] CD4+ T-cell counts were calculated as the mean of the two most recent values available on or before study entry.


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Cumulative Probability of First Virologic Failure by Week 96   [ Time Frame: From study entry to week 96 ]

2.  Primary:   Cumulative Incidence of Discontinuation of the RAL or PI Component of Randomized Treatment for Toxicity by Week 96   [ Time Frame: From study entry to week 96 ]

3.  Secondary:   Cumulative Incidence of First Adverse Event by Week 96   [ Time Frame: From study entry to week 96 ]

4.  Secondary:   Cumulative Probability of Time to Loss of Virologic Response (TLOVR) by Week 96   [ Time Frame: From study entry to week 96 ]

5.  Secondary:   Presence of Mutations Associated With NRTI Resistance   [ Time Frame: At the virologic failure at any time throughout the study (up to 213 weeks) ]

6.  Secondary:   Presence of Mutations Associated With ATV/RTV or DRV/RTV Resistance   [ Time Frame: At the virologic failure at any time throughout the study (up to 213 weeks) ]

7.  Secondary:   Presence of Mutations Associated With INI Resistance   [ Time Frame: At the virologic failure at any time throughout the study (up to 213 weeks) ]

8.  Secondary:   CD4+ T-cell Count   [ Time Frame: At Weeks 24, 48, 96, and 144 ]

9.  Secondary:   CD4+ T-cell Count Changes From Baseline   [ Time Frame: Study entry to weeks 24, 48, 96, and 144 ]

10.  Secondary:   Incidence of Death or AIDS Defining Events (CDC Category C)   [ Time Frame: Study entry to off-study at any time throughout the study (up to 213 weeks), participant follow-up time was variable ]

11.  Secondary:   Incidence of Targeted Serious Non-AIDS Defining Events (Renal Failure, Liver Disease, Serious Metabolic Disorder, and CVD)   [ Time Frame: Study entry to off-study at any time throughout the study (up to 213 weeks), participant follow-up time was variable ]

12.  Secondary:   Change in Fasting Total Cholesterol Level From Baseline   [ Time Frame: Study entry to weeks 48, 96, and 144 ]

13.  Secondary:   Change in Fasting HDL Cholesterol Level From Baseline   [ Time Frame: Study entry to weeks 48, 96, and 144 ]

14.  Secondary:   Change in Fasting Triglycerides Level From Baseline   [ Time Frame: Study entry to weeks 48, 96, and 144 ]

15.  Secondary:   Change in Fasting Plasma Glucose Level From Baseline   [ Time Frame: Study entry to weeks 48, 96, and 144 ]

16.  Secondary:   Change in Framingham 10-year Risk of MI or Coronary Death From Baseline   [ Time Frame: Study entry to weeks 48, 96, and 144 ]

17.  Secondary:   Change in Waist Circumference From Baseline   [ Time Frame: Study entry to weeks 48, 96, and 144 ]

18.  Secondary:   Change in Waist:Height Ratio From Baseline   [ Time Frame: Study entry to weeks 48, 96, and 144 ]

19.  Secondary:   Self-reported Adherence   [ Time Frame: At Weeks 4, 24, 48, 96, and 144 ]


  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:

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


Responsible Party: AIDS Clinical Trials Group
ClinicalTrials.gov Identifier: NCT00811954     History of Changes
Other Study ID Numbers: ACTG A5257
1U01AI068636 ( US NIH Grant/Contract Award Number )
Study First Received: December 18, 2008
Results First Received: June 23, 2014
Last Updated: September 4, 2014
Health Authority: United States: Federal Government