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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: May 24, 2016
Last verified: May 2016
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
A total of 104 exclusions among 517 enrolled to active screening but prior to assignment and dispensation of study treatment were due to any of the following: no resistance/tropism test results, not willing to accept any 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 for 2 periods

Period 1:   First Year of Follow-up
    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]   168 [1]   50 
NOT COMPLETED   12   11   3 
Death                7                0                0 
Severe debilitation                1                0                1 
Withdrawal by Subject                3                6                1 
Lost to Follow-up                1                5                1 
[1] Completed refers to completing first 48 weeks of follow-up.

Period 2:   2nd Year of Follow-up
    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   169   168   50 
COMPLETED   158   159   44 
NOT COMPLETED   11   9   6 
Death                4                1                2 
Withdrawal by Subject                0                1                2 
Lost to Follow-up                6                7                2 
Clinic site closure                1                0                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.
Everyone randomized (ITT study sample), plus non-randomized group.

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 
Overall Participants Analyzed 
[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 
CD4 count, continuous 
[Units: Cells/mm^3]
Mean (Standard Deviation)
 252.3  (194.9)   245.6  (195.1)   154.8  (170.1)   236.9  (194.2) 
Plasma HIV-1 RNA, continuous 
[Units: Log10 copies/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:   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 ]

3.  Secondary:   Time From Treatment Dispensation to First Study ARV Modification (Excluding NRTIs, if Applicable)   [ Time Frame: From treatment dispensation to week 96 study visit ]

4.  Secondary:   Time From Randomization to Discontinuation of Randomized NRTI Component of Study Treatment   [ Time Frame: From randomization to week 96 study visit ]

5.  Secondary:   Time From Randomization to Confirmed Virological Failure   [ Time Frame: From randomization to week 96 study visit ]

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

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

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

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

10.  Secondary:   Change in Cardiovascular Risk Score From Baseline   [ Time Frame: At Weeks 24, 48, and 96 ]

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

12.  Secondary:   Time From Treatment Dispensation to Serious Non-AIDS-defining Events   [ Time Frame: From treatment initiation to week 96 study visit ]

13.  Secondary:   Number of Participants With 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 (up to 96 weeks) ]

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

15.  Secondary:   Participants With Newly Acquired HIV Drug Resistance Between Study Entry and Confirmed Virologic Failure   [ Time Frame: Between baseline and confirmed virologic failure (up to 96 weeks) ]


  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: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00537394     History of Changes
Other Study ID Numbers: A5241
10395 ( Registry Identifier: DAIDS ES )
ACTG A5241
OPTIONS
Study First Received: September 27, 2007
Results First Received: June 14, 2013
Last Updated: May 24, 2016
Health Authority: United States: Food and Drug Administration