Bone, Immunologic, and Virologic Effects of a Antiretroviral Regimen

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
AIDS Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT01400412
First received: July 21, 2011
Last updated: June 17, 2015
Last verified: June 2015
Results First Received: June 17, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: HIV-1 Infection
Interventions: Drug: Darunavir
Drug: Ritonavir
Drug: Tenofovir disoproxil fumarate
Drug: Emtricitabine
Drug: Placebo for Tenofovir disoproxil fumarate
Drug: Placebo for Maraviroc
Drug: Maraviroc

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
A5303 opened under version 1.0 on 12/4/11, and the first participant was enrolled on 1/17/12. Accrual to the study closed on 6/12/13, with a total of 262 participants enrolled at 38 sites

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
MVC Arm (DRV/r + MVC + FTC + TDF Placebo)

Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Maraviroc 150 mg PO QD + Emtricitabine 200 mg PO QD + Placebo for Tenofovir disoproxil fumarate PO QD

Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet.

Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food.

Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule.

Placebo for Tenofovir disoproxil fumarate: Placebo for tenofovir disoproxil fumarate was administered orally once a day as one tablet.

TDF Arm (DRV/r + TDF + FTC + MVC Placebo)

Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Emtricitabine 200 mg PO QD + Tenofovir disoproxil fumarate 300 mg PO QD + Placebo for Maraviroc PO QD

Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet.

Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food.

Tenofovir disoproxil fumarate: Tenofovir disoproxil fumarate was administered orally as one 300 mg tablet once a day.

Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule.

Placebo for Maraviroc: Placebo for maraviroc was administered orally once a day as one 150 mg tablet.


Participant Flow:   Overall Study
    MVC Arm (DRV/r + MVC + FTC + TDF Placebo)     TDF Arm (DRV/r + TDF + FTC + MVC Placebo)  
STARTED     130     132  
COMPLETED     120     115  
NOT COMPLETED     10     17  
Lost to Follow-up                 4                 7  
Withdrawal by Subject                 3                 4  
Unable to complete                 3                 3  
Never started study treatment                 0                 3  



  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.
Participants who started study treatment

Reporting Groups
  Description
MVC Arm (DRV/r + MVC + FTC + TDF Placebo)

Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Maraviroc 150 mg PO QD + Emtricitabine 200 mg PO QD + Placebo for Tenofovir disoproxil fumarate PO QD

Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet.

Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food.

Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule.

Placebo for Tenofovir disoproxil fumarate: Placebo for tenofovir disoproxil fumarate was administered orally once a day as one tablet.

TDF Arm (DRV/r + TDF + FTC + MVC Placebo)

Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Emtricitabine 200 mg PO QD + Tenofovir disoproxil fumarate 300 mg PO QD + Placebo for Maraviroc PO QD

Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet.

Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food.

Tenofovir disoproxil fumarate: Tenofovir disoproxil fumarate was administered orally as one 300 mg tablet once a day.

Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule.

Placebo for Maraviroc: Placebo for maraviroc was administered orally once a day as one 150 mg tablet.

Total Total of all reporting groups

Baseline Measures
    MVC Arm (DRV/r + MVC + FTC + TDF Placebo)     TDF Arm (DRV/r + TDF + FTC + MVC Placebo)     Total  
Number of Participants  
[units: participants]
  130     129     259  
Age  
[units: years]
Median (Inter-Quartile Range)
  33   (26 to 42)     33   (26 to 42)     33   (26 to 42)  
Age, Customized  
[units: participants]
     
18-29 Years     49     48     97  
30-39 Years     40     41     81  
40-49 Years     26     24     50  
>=50 Years     15     16     31  
Gender  
[units: participants]
     
Female     15     9     24  
Male     115     120     235  
Race/Ethnicity, Customized  
[units: participants]
     
White non-Hispanic     57     59     116  
Black non-Hispanic     45     33     78  
Hispanic (regardless of race)     24     34     58  
Asian, Pacific Islander     2     1     3  
American Indian, Alaskan Native     0     1     1  
More than one race     2     1     3  
Region of Enrollment  
[units: participants]
     
United States     127     127     254  
Puerto Rico     3     2     5  
CD4 count  
[units: cells/mm^3]
Median (Inter-Quartile Range)
  389   (295 to 496)     392   (290 to 518)     390   (294 to 517)  
HIV-1 RNA  
[units: log10┬ácopies/mL]
Median (Inter-Quartile Range)
  4.59   (3.91 to 5.07)     4.47   (4.02 to 4.91)     4.50   (3.97 to 5.00)  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Percent Change From Baseline in Total Hip Bone Mineral Density (BMD)   [ Time Frame: Week 0, week 48 ]

2.  Secondary:   Percent Change in Lumbar Spine Bone Mineral Density (BMD)   [ Time Frame: Week 0, week 48 ]

3.  Secondary:   Change in CD4 Count From Baseline to Week 24   [ Time Frame: Week 0, week 24 ]

4.  Secondary:   Change in CD4 Count From Baseline to Week 48   [ Time Frame: Week 0, week 48 ]

5.  Secondary:   Number of Participants Who Experienced Bone Fractures   [ Time Frame: From study treatment initiation to week 48 ]

6.  Secondary:   Cumulative Probability of Virologic Failure by Week 48   [ Time Frame: From study treatment initiation to week 48 ]

7.  Secondary:   Number of Participants Who Died During the Study   [ Time Frame: From study treatment initiation to week 48 ]

8.  Secondary:   Number of Participants Who Developed Grade 3 or 4 Primary Adverse Events   [ Time Frame: From study treatment initiation to week 48 ]

9.  Secondary:   Percent Change in Expression of CD38 on CD8+ T Cells From Baseline   [ Time Frame: At weeks 0, 24, and 48 ]
Results not yet reported.   Anticipated Reporting Date:   03/2016   Safety Issue:   No

10.  Secondary:   Percent Change in Expression of HLA-DR on CD8+ T Cells From Baseline   [ Time Frame: At weeks 0, 24, and 48 ]
Results not yet reported.   Anticipated Reporting Date:   03/2016   Safety Issue:   No

11.  Secondary:   Percent Change in Expression of Ki67 on CD8+ T Cells From Baseline   [ Time Frame: At weeks 0, 24, and 48 ]
Results not yet reported.   Anticipated Reporting Date:   03/2016   Safety Issue:   No

12.  Secondary:   Percent Change in Expression of CD28 on CD8+ T Cells From Baseline   [ Time Frame: At weeks 0, 24, and 48 ]
Results not yet reported.   Anticipated Reporting Date:   03/2016   Safety Issue:   No

13.  Secondary:   Percent Change in Expression of CD57 on CD8+ T Cells From Baseline   [ Time Frame: At weeks 0, 24, and 48 ]
Results not yet reported.   Anticipated Reporting Date:   03/2016   Safety Issue:   No

14.  Secondary:   Percent Change in Expression of PK1 on CD8+ T Cells From Baseline   [ Time Frame: At weeks 0, 24, and 48 ]
Results not yet reported.   Anticipated Reporting Date:   03/2016   Safety Issue:   No

15.  Secondary:   Change in Levels of IL-6 From Baseline   [ Time Frame: At weeks 0, 24, and 48 ]
Results not yet reported.   Anticipated Reporting Date:   03/2016   Safety Issue:   No

16.  Secondary:   Change in Level of hsCRP From Baseline   [ Time Frame: At weeks 0, 24, and 48 ]
Results not yet reported.   Anticipated Reporting Date:   03/2016   Safety Issue:   No

17.  Secondary:   Change in Levels of Plasma LPS From Baseline   [ Time Frame: At weeks 0, 24, and 48 ]
Results not yet reported.   Anticipated Reporting Date:   03/2016   Safety Issue:   No

18.  Secondary:   Change in Levels of Soluble CD14 From Baseline   [ Time Frame: At weeks 0, 24, and 48 ]
Results not yet reported.   Anticipated Reporting Date:   03/2016   Safety Issue:   No

19.  Secondary:   Change in Level of Peripheral β7hi CD4+ T Cells From Baseline   [ Time Frame: At weeks 0, 24, and 48 ]
Results not yet reported.   Anticipated Reporting Date:   03/2016   Safety Issue:   No

20.  Secondary:   Change in Levels of D-dimer From Baseline   [ Time Frame: At weeks 0, 24, and 48 ]
Results not yet reported.   Anticipated Reporting Date:   03/2016   Safety Issue:   No

21.  Secondary:   CD8+ T-cell Change From Baseline   [ Time Frame: At weeks 0, 24, and 48 ]
Results not yet reported.   Anticipated Reporting Date:   03/2016   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
No text entered.


  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 and Scientific Systems
phone: 301-628-3313
e-mail: ACTGCT.Gov@s-3.com


No publications provided


Responsible Party: AIDS Clinical Trials Group
ClinicalTrials.gov Identifier: NCT01400412     History of Changes
Other Study ID Numbers: ACTG A5303, 1U01AI068636
Study First Received: July 21, 2011
Results First Received: June 17, 2015
Last Updated: June 17, 2015
Health Authority: United States: Federal Government