Atorvastatin on Biomarkers of Inflammation, Coagulopathy, Angiogenesis & T-cells

This study has been completed.
Sponsor:
Collaborators:
Pfizer
Information provided by (Responsible Party):
AIDS Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT01351025
First received: November 8, 2010
Last updated: August 4, 2015
Last verified: July 2015
Results First Received: May 1, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Double Blind (Subject, Caregiver, Outcomes Assessor);   Primary Purpose: Treatment
Condition: HIV-1 Infection
Interventions: Drug: atorvastatin
Drug: placebo for atorvastin

  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
A5275 opened under version 1.0 on April 7, 2011, and the first participant was randomized on April 14, 2011. Accrual to the study closed on May 31, 2013, with a total of 98 participants enrolled at 31 sites.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Four enrolled participants did not start study treatment (3 from arm A and 1 from arm B) due to enrollment error and noncompliance. These 4 participants were not included in the study efficacy or safety analyses.

Reporting Groups
  Description
Arm A: Atorvastatin / Placebo

At study entry (week 0), participants continued the entry boosted PI-based antiretroviral regimen (not provided by the study) and initiated atorvastatin at a daily dose of 10 mg for 4 weeks. If no symptoms or lab findings suggestive of atorvastatin toxicity were found, the dose of atorvastatin was increased to 20 mg daily at the week 4 visit. At week 20, atorvastatin was stopped for a 4-week washout period.

At week 24, placebo was started for 4 weeks. If no symptoms or lab findings suggestive of toxicity were found, the placebo dose was doubled at week 28. At week 44, the placebo was stopped to allow for another 4-week washout period.

atorvastatin: 10 mg daily for 4 weeks, if no symptoms or lab findings suggestive of atorvastatin toxicity, dose increase to 20 mg daily from week 4 - week 20

Arm B: Placebo / Atorvastatin

At study entry (week 0), participants continued the entry boosted PI-based antiretroviral regimen (not provided by the study) and initiated placebo for 4 weeks. If no symptoms or lab findings suggestive of toxicity were found, the dose of placebo was doubled at the week 4 visit. At week 20, the placebo was stopped for a 4-week washout period.

At week 24, atorvastatin was started at a daily dose of 10 mg for 4 weeks. If no symptoms or lab findings suggestive of atorvastatin toxicity were found, the dose of atorvastatin was increased to 20 mg daily at week 28. At week 44, atorvastatin was stopped to allow for another 4-week washout period.

atorvastatin: Starting at week 24, 10 mg daily for 4 weeks. If no symptoms or lab findings suggestive of atorvastatin toxicity were found, 20 mg daily from week 28- week 44.


Participant Flow for 4 periods

Period 1:   Week 0 - 20
    Arm A: Atorvastatin / Placebo     Arm B: Placebo / Atorvastatin  
STARTED     46     48  
COMPLETED     43     47  
NOT COMPLETED     3     1  
Lost to Follow-up                 2                 1  
Withdrawal by Subject                 1                 0  

Period 2:   Week 20 - 24
    Arm A: Atorvastatin / Placebo     Arm B: Placebo / Atorvastatin  
STARTED     43     47  
COMPLETED     43     47  
NOT COMPLETED     0     0  

Period 3:   Week 24 - 44
    Arm A: Atorvastatin / Placebo     Arm B: Placebo / Atorvastatin  
STARTED     43     47  
COMPLETED     42     43  
NOT COMPLETED     1     4  
Lost to Follow-up                 0                 2  
Site closed                 0                 1  
unable to get to clinic                 1                 1  

Period 4:   Week 44 - 48
    Arm A: Atorvastatin / Placebo     Arm B: Placebo / Atorvastatin  
STARTED     42     43  
COMPLETED     42     43  
NOT COMPLETED     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.
Participants who started study treatment are included

Reporting Groups
  Description
Arm A: Atorvastatin / Placebo

At study entry (week 0), participants continued the entry boosted PI-based antiretroviral regimen (not provided by the study) and initiated atorvastatin at a daily dose of 10 mg for 4 weeks. If no symptoms or lab findings suggestive of atorvastatin toxicity were found, the dose of atorvastatin was increased to 20 mg daily at the week 4 visit. At week 20, atorvastatin was stopped for a 4-week washout period.

At week 24, placebo was started for 4 weeks. If no symptoms or lab findings suggestive of toxicity were found, the placebo dose was doubled at week 28. At week 44, the placebo was stopped to allow for another 4-week washout period.

atorvastatin: 10 mg daily for 4 weeks, if no symptoms or lab findings suggestive of atorvastatin toxicity, dose increase to 20 mg daily from week 4 - week 20

Arm B: Placebo / Atorvastatin

At study entry (week 0), participants continued the entry boosted PI-based antiretroviral regimen (not provided by the study) and initiated placebo for 4 weeks. If no symptoms or lab findings suggestive of toxicity were found, the dose of placebo was doubled at the week 4 visit. At week 20, the placebo was stopped for a 4-week washout period.

At week 24, atorvastatin was started at a daily dose of 10 mg for 4 weeks. If no symptoms or lab findings suggestive of atorvastatin toxicity were found, the dose of atorvastatin was increased to 20 mg daily at week 28. At week 44, atorvastatin was stopped to allow for another 4-week washout period.

atorvastatin: Starting at week 24, 10 mg daily for 4 weeks. If no symptoms or lab findings suggestive of atorvastatin toxicity were found, 20 mg daily from week 28- week 44.

Total Total of all reporting groups

Baseline Measures
    Arm A: Atorvastatin / Placebo     Arm B: Placebo / Atorvastatin     Total  
Number of Participants  
[units: participants]
  46     48     94  
Age  
[units: years]
Median (Inter-Quartile Range)
  47   (39 to 55)     50   (42 to 55)     48   (41 to 55)  
Age, Customized  
[units: participants]
     
18-29 Years     3     2     5  
30-39 Years     9     6     15  
40-49 Years     16     16     32  
50-59 Years     14     21     35  
>=60 Years     4     3     7  
Gender  
[units: participants]
     
Female     17     13     30  
Male     29     35     64  
Race/Ethnicity, Customized  
[units: participants]
     
White non-Hispanic     10     13     23  
Black non-Hispanic     21     22     43  
Hispanic (regardless of race)     14     13     27  
Asian, Pacific Islander     1     0     1  
Region of Enrollment  
[units: participants]
     
United States     46     48     94  
HIV-1 RNA  
[units: participants]
     
< assay lower limit     46     47     93  
>= assay lower limit     0     1     1  
CD4 count  
[units: cells/mm^3]
Median (Inter-Quartile Range)
  587   (373 to 732)     545   (424 to 689)     552   (412 to 714)  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Difference Between [Change From Week 24 to Week 44] and [Change From Baseline to Week 20] in log10 IL-6   [ Time Frame: baseline, week 20, week 24, and week 44 ]

2.  Primary:   Difference Between [Change From Week 24 to Week 44] and [Change From Baseline to Week 20] in CD4+ T-cell Activation Percent   [ Time Frame: baseline, week 20, week 24, and week 44 ]

3.  Primary:   Difference Between [Change From Week 24 to Week 44] and [Change From Baseline to Week 20] in log10 D-dimer   [ Time Frame: baseline, week 20, week 24, and week 44 ]

4.  Primary:   Difference Between [Change From Week 24 to Week 44] and [Change From Baseline to Week 20] in CD8+ T-cell Activation Percent   [ Time Frame: baseline, week 20, week 24, and week 44 ]

5.  Secondary:   Number of Participants With Safety Endpoints Before Study Treatment Cross-over (Baseline to Week 24)   [ Time Frame: week 0 to week 24 ]

6.  Secondary:   Number of Participants With Safety Endpoints After Study Treatment Cross-over (Week 24 to Week 48)   [ Time Frame: week 24 to week 48 ]

7.  Secondary:   Difference Between [Change From Week 24 to Week 44] and Change From [Baseline to Week 20] in Biomarkers   [ Time Frame: baseline, week 20, week 24, and week 44 ]
Results not yet reported.   Anticipated Reporting Date:   08/2015   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, Inc.
phone: 301-628-3313
e-mail: ACTGCT.Gov@s-3.com


No publications provided


Responsible Party: AIDS Clinical Trials Group
ClinicalTrials.gov Identifier: NCT01351025     History of Changes
Other Study ID Numbers: ACTG A5275, 1U01AI068636
Study First Received: November 8, 2010
Results First Received: May 1, 2015
Last Updated: August 4, 2015
Health Authority: United States: Federal Government