Optimizing Treatment for Treatment-Experienced, HIV-Infected People

This study has been completed.
Sponsor:
Collaborator:
AIDS Clinical Trials Group
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00537394
First received: September 27, 2007
Last updated: October 13, 2014
Last verified: October 2014
Results First Received: June 14, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: HIV Infections
Interventions: Drug: Enfuvirtide
Drug: Raltegravir
Drug: Darunavir
Drug: Tipranavir
Drug: Etravirine
Drug: Maraviroc

  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
Subjects recruited between February 2008 and May 2011 from participating ACTG, IMPAACT, and ATN network sites located in the continental US and Puerto Rico.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Exclusions prior to assignment due to any of the following: no resistance/tropism test results from which individualized regimens/NRTIs could be identified, unwillingness to accept any of recommended ARV study regimens, changes to current PI based ARV regimen or non-adherence, or changes with respect to eligibility criteria.

Reporting Groups
  Description
Add NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0) [Arm A]Individualized ARV study regimen with antiretroviral potency defined as continuous phenotype sensitivity score (cPSS) greater than 2.0 recommended and chosen prior to randomization. To this regimen, an individualized NRTI combination of at least 2 drugs from this class, chosen prior to randomization, was also started.
Omit NRTIs (Randomized) From Individualized Regimen(cPSS > 2) [Arm B] Individualized ARV study regimen with antiretroviral potency defined as continuous phenotype sensitivity score (cPSS) greater than 2.0 recommended and chosen prior to randomization. To this regimen, an individualized NRTI combination of at least 2 drugs from this class, chosen prior to randomization, was omitted, and any NRTIs the participant had been taking prior to randomization were to be permanently discontinued.
Non-randomized Group: Add NRTIs to Individual Regimen cPSS <=2 [Non-randomized Group C] : Among persons whose ARV resistance and history profile precluded any of the 20 possible ARV regimens having high enough potential potency (cPSS <=2), treatment was assigned rather than being a randomized. To their regimen, individualized NRTI combination of at least 2 drugs from this class were added in order to form the most potent ARV regimen possible.

Participant Flow:   Overall Study
    Add NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0)     Omit NRTIs (Randomized) From Individualized Regimen(cPSS > 2)     Non-randomized Group: Add NRTIs to Individual Regimen cPSS <=2  
STARTED     181     179     53  
COMPLETED     169 [1]   165 [1]   46  
NOT COMPLETED     12     14     7  
Death                 7                 0                 0  
Severe debilitation                 1                 0                 1  
Missed Week 48 visit but not lost                 0                 3                 4  
Withdrawal by Subject                 3                 6                 1  
Lost to Follow-up                 1                 5                 1  
[1] Completed refers to completing first 48 weeks of follow-up.



  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.
Everyone randomized (ITT study sample), plus non-randomized group. Post-baseline results for non-randomized group (n=53) for outcomes for which this non-randomized group was evaluated, will be added when these results are available

Reporting Groups
  Description
Add NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0) Individualized ARV study regimen with antiretroviral potency defined as continuous phenotype sensitivity score (cPSS) greater than 2.0 recommended and chosen prior to randomization. To this regimen, an individualized NRTI combination of at least 2 drugs from this class, chosen prior to randomization, was also started.
Omit NRTIs (Randomized) From Individualized Regimen(cPSS > 2) Individualized ARV study regimen with antiretroviral potency defined as continuous phenotype sensitivity score (cPSS) greater than 2.0 recommended and chosen prior to randomization. To this regimen, an individualized NRTI combination of at least 2 drugs from this class, chosen prior to randomization, was omitted, and any NRTIs the participant had been taking prior to randomization were to be permanently discontinued.
Non-randomized Group: Add NRTIs to Individual Regimen cPSS <=2 Among persons whose ARV resistance and history profile precluded any of the 20 possible ARV regimens having high enough potential potency (cPSS <=2), treatment was assigned rather than being a randomized. To their regimen, individualized NRTI combination of at least 2 drugs from this class were added in order to form the most potent ARV regimen possible.
Total Total of all reporting groups

Baseline Measures
    Add NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0)     Omit NRTIs (Randomized) From Individualized Regimen(cPSS > 2)     Non-randomized Group: Add NRTIs to Individual Regimen cPSS <=2     Total  
Number of Participants  
[units: participants]
  181     179     53     413  
Age  
[units: participants]
       
<=18 years     6     8     3     17  
Between 18 and 65 years     173     168     50     391  
>=65 years     2     3     0     5  
Age  
[units: years]
Mean ± Standard Deviation
  44.7  ± 10.8     44.1  ± 11.7     43.1  ± 10.7     44.3  ± 11.2  
Gender  
[units: participants]
       
Female     46     47     6     99  
Male     135     132     47     314  
Ethnicity (NIH/OMB)  
[units: participants]
       
Hispanic or Latino     37     46     14     97  
Not Hispanic or Latino     141     132     38     311  
Unknown or Not Reported     3     1     1     5  
Race (NIH/OMB)  
[units: participants]
       
American Indian or Alaska Native     3     2     1     6  
Asian     0     4     1     5  
Native Hawaiian or Other Pacific Islander     0     1     0     1  
Black or African American     81     72     20     173  
White     88     87     29     204  
More than one race     1     2     0     3  
Unknown or Not Reported     8     11     2     21  
Region of Enrollment  
[units: participants]
       
United States     181     179     53     413  
Study-Specific Measure  
[units: cells/mm^3]
Mean ± Standard Deviation
  252.3  ± 194.9     245.6  ± 195.1     154.8  ± 170.1     236.9  ± 194.2  
Study-Specific Measure  
[units: log10┬ácopies/mL]
Median ( Inter-Quartile Range )
  4.2  
  ( 3.6 to 4.7 )  
  4.2  
  ( 3.6 to 4.6 )  
  4.4  
  ( 4.1 to 4.8 )  
  4.2  
  ( 3.6 to 4.6 )  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Percent of Participants With Regimen Failure, Defined as a Confirmed Virologic Failure or Discontinuation of Randomized NRTI Component of Study Treatment   [ Time Frame: From study entry to end of Week 48 evaluation window ]

2.  Secondary:   Participants With Plasma HIV-1 Viral Load < 50 Copies/ml   [ Time Frame: At Weeks 24, 48, 96 ]

3.  Secondary:   Change in Plasma HIV-1 Viral Load From Baseline to Week 1   [ Time Frame: From baseline to Week 1 evaluation ]

4.  Secondary:   Change in Summarized Quality of Life Score   [ Time Frame: At study entry and Weeks 24, 48, 96 ]

5.  Secondary:   Number of Participants Self-reporting Non-adherence to Assigned Study ARVS (Excluding NRTIs, if Applicable)   [ Time Frame: At Weeks 24 and 48 ]

6.  Secondary:   Change in CD4 Count From Baseline   [ Time Frame: From study entry to Weeks 48 and 96 ]

7.  Secondary:   Change in Fasting Non-HDL Cholesterol From Baseline   [ Time Frame: From study entry to Weeks 24, 48 ]

8.  Secondary:   Time From Treatment Dispensation to First Grade 3 or Higher (and at Least One Grade Higher Than Baseline) Signs/Symptom or Laboratory Abnormality   [ Time Frame: From treatment dispensation to week 96 study visit ]
Results not yet reported.   Anticipated Reporting Date:   12/2014   Safety Issue:   Yes

9.  Secondary:   Time From Treatment Dispensation to First Study ARV Modification (Excluding NRTIs, if Applicable)   [ Time Frame: From treatment dispensation to week 96 study visit ]
Results not yet reported.   Anticipated Reporting Date:   12/2014   Safety Issue:   No

10.  Secondary:   Time From Randomization to Discontinuation of Randomized NRTI Component of Study Treatment   [ Time Frame: From randomization to week 96 study visit ]
Results not yet reported.   Anticipated Reporting Date:   12/2014   Safety Issue:   No

11.  Secondary:   Time From Randomization to Confirmed Virological Failure   [ Time Frame: From randomization to week 96 study visit ]
Results not yet reported.   Anticipated Reporting Date:   12/2014   Safety Issue:   No

12.  Secondary:   Change in Cardiovascular Risk Score From Baseline   [ Time Frame: At Weeks 24, 48, and 96 ]
Results not yet reported.   Anticipated Reporting Date:   12/2014   Safety Issue:   No

13.  Secondary:   Time From Randomization to Serious Non-AIDS-defining Events   [ Time Frame: From randomization to week 96 study visit ]
Results not yet reported.   Anticipated Reporting Date:   12/2014   Safety Issue:   Yes

14.  Secondary:   Change in Virus Co-receptor Tropism Among Those With R5-only Tropic Virus at Study Entry   [ Time Frame: From study entry to time of confirmed virological failure ]
Results not yet reported.   Anticipated Reporting Date:   12/2014   Safety Issue:   No

15.  Secondary:   Percent of Participants With Newly Acquired HIV Drug Resistance Between Study Entry and Confirmed Virologic Failure   [ Time Frame: Between baseline and confirmed virologic failure ]
Results not yet reported.   Anticipated Reporting Date:   12/2014   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:

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00537394     History of Changes
Other Study ID Numbers: A5241, 10395, ACTG A5241, OPTIONS
Study First Received: September 27, 2007
Results First Received: June 14, 2013
Last Updated: October 13, 2014
Health Authority: United States: Food and Drug Administration