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Effect of Addition of Raltegravir (MK-0518) to PI- or NNRTI-Based ART Regimens in HIV Infected Subjects With Undetectable Viral Load

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00515827
First received: August 10, 2007
Last updated: November 25, 2013
Last verified: November 2013
Results First Received: January 25, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Crossover Assignment;   Masking: Double Blind (Subject, Caregiver);   Primary Purpose: Treatment
Condition: HIV Infections
Interventions: Drug: Raltegravir (MK-0518)
Drug: Placebo

  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
No text entered.

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
Raltegravir Then Placebo (Arm A) 400 mg raltegravir (MK-0518) administered twice daily in addition to optimized background regimen (OBR) from entry to Week 12; halt raltegravir at Week 12 and add placebo twice daily for 12 weeks
Placebo Then Raltegravir (Arm B) Placebo administered twice daily in addition to OBR from entry until Week 12; halt placebo at Week 12 and add 400 mg raltegravir tablet twice daily for 12 weeks.

Participant Flow for 2 periods

Period 1:   First Intervention (12 Weeks)
    Raltegravir Then Placebo (Arm A)     Placebo Then Raltegravir (Arm B)  
STARTED     27     26  
COMPLETED     26     25  
NOT COMPLETED     1     1  
Unwilling to adhere to study requirement                 1                 1  

Period 2:   Second Intervention (12 Weeks)
    Raltegravir Then Placebo (Arm A)     Placebo Then Raltegravir (Arm B)  
STARTED     26     25  
COMPLETED     25     25  
NOT COMPLETED     1     0  
Consent withdraw                 1                 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.
No text entered.

Reporting Groups
  Description
Raltegravir Then Placebo (Arm A) 400 mg raltegravir (MK-0518) administered twice daily in addition to optimized background regimen (OBR) from entry to Week 12; halt raltegravir at Week 12 and add placebo twice daily for 12 weeks
Placebo Then Raltegravir (Arm B) Placebo administered twice daily in addition to OBR from entry until Week 12; halt placebo at Week 12 and add 400 mg raltegravir tablet twice daily for 12 weeks.
Total Total of all reporting groups

Baseline Measures
    Raltegravir Then Placebo (Arm A)     Placebo Then Raltegravir (Arm B)     Total  
Number of Participants  
[units: participants]
  27     26     53  
Age  
[units: participants]
     
<=18 years     0     0     0  
Between 18 and 65 years     27     24     51  
>=65 years     0     2     2  
Age  
[units: years]
Mean ± Standard Deviation
  50  ± 7     49  ± 11     49  ± 8  
Gender  
[units: participants]
     
Female     3     2     5  
Male     24     24     48  
Region of Enrollment  
[units: participants]
     
United States     27     26     53  



  Outcome Measures
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1.  Primary:   HIV-1 RNA Level   [ Time Frame: At Weeks 10 and 12 ]

Measure Type Primary
Measure Title HIV-1 RNA Level
Measure Description HIV-1 RNA level, as measured by single copy assay, averaged at weeks 10 and 12. The quantification limit of single copy assay was determined by the volume of plasma tested. When averaging the week 10 and 12 measurements, if one of both measurements were below the single copy assay lower limits, the lower limit of quantification was used to compute the average and the result was treated as below the averaged value.
Time Frame At Weeks 10 and 12  
Safety Issue No  

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.
49 subjects who were on study treatment before week 10 and did not experience virologic failure by week 12

Reporting Groups
  Description
Raltegravir (Arm A) 400 mg raltegravir (MK-0518) administered twice daily in addition to optimized background regimen (OBR) from entry to Week 12
Placebo (Arm B) Placebo administered twice daily in addition to OBR from entry until Week 12

Measured Values
    Raltegravir (Arm A)     Placebo (Arm B)  
Number of Participants Analyzed  
[units: participants]
  25     24  
HIV-1 RNA Level  
[units: copies/mL]
Median ( Inter-Quartile Range )
  1.2  
  ( 0.4 to 5.0 )  
  1.7  
  ( 0.5 to 2.3 )  


Statistical Analysis 1 for HIV-1 RNA Level
Groups [1] All groups
Method [2] Wilcoxon (Mann-Whitney)
P Value [3] 0.546
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-value is 2-sided and is not adjusted for multiple comparisons



2.  Secondary:   Change in HIV-1 RNA Level   [ Time Frame: At pre-entry, entry, weeks 10 and 12 ]

Measure Type Secondary
Measure Title Change in HIV-1 RNA Level
Measure Description Change in HIV-1 RNA level, as measured by single copy assay, from baseline to weeks 10/12 . When averaging the measurements at pre-entry and entry, and at weeks 10 and 12, measurements below the lower limit of quantification (LLQ) were imputed a value of the LLQ divided by 2.
Time Frame At pre-entry, entry, weeks 10 and 12  
Safety Issue No  

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.
All participants who were on study treatment and had not experienced virologic failure

Reporting Groups
  Description
Raltegravir (Arm A) 400 mg raltegravir (MK-0518) administered twice daily in addition to optimized background regimen (OBR) from entry to Week 12
Placebo (Arm B) Placebo administered twice daily in addition to OBR from entry until Week 12

Measured Values
    Raltegravir (Arm A)     Placebo (Arm B)  
Number of Participants Analyzed  
[units: participants]
  25     24  
Change in HIV-1 RNA Level  
[units: copies/mL]
Median ( Inter-Quartile Range )
  -0.2  
  ( -1.2 to 0.2 )  
  -0.1  
  ( -0.6 to 0.4 )  

No statistical analysis provided for Change in HIV-1 RNA Level



3.  Secondary:   Change in Total CD4 Cell Count   [ Time Frame: At pre-entry, entry, and week 12 ]

Measure Type Secondary
Measure Title Change in Total CD4 Cell Count
Measure Description CD4 cell counts were assessed by flow cytometry at pre-entry and entry (the baseline value was the average of the two measurements) and at week 12
Time Frame At pre-entry, entry, and week 12  
Safety Issue No  

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.
All participants who were on study treatment and had not experienced virologic failure

Reporting Groups
  Description
Raltegravir (Arm A) 400 mg raltegravir (MK-0518) administered twice daily in addition to optimized background regimen (OBR) from entry to Week 12
Placebo (Arm B) Placebo administered twice daily in addition to OBR from entry until Week 12

Measured Values
    Raltegravir (Arm A)     Placebo (Arm B)  
Number of Participants Analyzed  
[units: participants]
  23     24  
Change in Total CD4 Cell Count  
[units: cells/mm^3]
Median ( Inter-Quartile Range )
  42  
  ( -52 to 80 )  
  -44  
  ( -117 to 49 )  

No statistical analysis provided for Change in Total CD4 Cell Count



4.  Secondary:   Change in Total CD8 Cell Count   [ Time Frame: At pre-entry, entry, and week 12 ]

Measure Type Secondary
Measure Title Change in Total CD8 Cell Count
Measure Description CD8 cell counts were assessed by flow cytometry at pre-entry and entry (the baseline value was the average of the two measurements) and at week 12
Time Frame At pre-entry, entry, and week 12  
Safety Issue No  

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.
All participants who were on study treatment and had not experienced virologic failure

Reporting Groups
  Description
Raltegravir (Arm A) 400 mg raltegravir (MK-0518) administered twice daily in addition to optimized background regimen (OBR) from entry to Week 12
Placebo (Arm B) Placebo administered twice daily in addition to OBR from entry until Week 12

Measured Values
    Raltegravir (Arm A)     Placebo (Arm B)  
Number of Participants Analyzed  
[units: participants]
  23     24  
Change in Total CD8 Cell Count  
[units: cells/mm^3]
Median ( Inter-Quartile Range )
  55  
  ( -76 to 140 )  
  -39  
  ( -152 to 77 )  

No statistical analysis provided for Change in Total CD8 Cell Count



5.  Secondary:   Change in CD4+/CD38+/HLA-DR+ Percent   [ Time Frame: At pre-entry, entry, and week 12 ]

Measure Type Secondary
Measure Title Change in CD4+/CD38+/HLA-DR+ Percent
Measure Description Level of CD4+ T-cell activation was determined by measuring the percentage of cells that expressed both the activation marker CD38 and Human leukocyte antigen (HLA)-DR. Levels measured at pre-entry and entry were averaged. Change from baseline to week 12 was defined as CD4+/CD38+/HLA-DR+% at week 12 minus CD4+/CD38+/HLA-DR+% at baseline.
Time Frame At pre-entry, entry, and week 12  
Safety Issue No  

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.
All participants who were on study treatment and had not experienced virologic failure

Reporting Groups
  Description
Raltegravir (Arm A) 400 mg raltegravir (MK-0518) administered twice daily in addition to optimized background regimen (OBR) from entry to Week 12
Placebo (Arm B) Placebo administered twice daily in addition to OBR from entry until Week 12

Measured Values
    Raltegravir (Arm A)     Placebo (Arm B)  
Number of Participants Analyzed  
[units: participants]
  20     23  
Change in CD4+/CD38+/HLA-DR+ Percent  
[units: % CD4 cells co-express CD38+ and HLA-DR+]
Median ( Inter-Quartile Range )
  -1  
  ( -2 to 1 )  
  0  
  ( -1 to 2 )  

No statistical analysis provided for Change in CD4+/CD38+/HLA-DR+ Percent



6.  Secondary:   Change in CD8+/CD38+/HLA-DR+ Percent   [ Time Frame: At pre-entry, entry, and week 12 ]

Measure Type Secondary
Measure Title Change in CD8+/CD38+/HLA-DR+ Percent
Measure Description Level of CD8+ T-cell activation was determined by measuring the percentage of cells that expressed both the activation marker CD38 and Human leukocyte antigen (HLA)-DR. Levels measured at pre-entry and entry were averaged. Change from baseline to week 12 was defined as CD8+/CD38+/HLA-DR+% at week 12 minus CD8+/CD38+/HLA-DR+% at baseline.
Time Frame At pre-entry, entry, and week 12  
Safety Issue No  

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.
All participants who stayed on study treatment and had not experienced virologic failures.

Reporting Groups
  Description
Raltegravir (Arm A) 400 mg raltegravir (MK-0518) administered twice daily in addition to optimized background regimen (OBR) from entry to Week 12
Placebo (Arm B) Placebo administered twice daily in addition to OBR from entry until Week 12

Measured Values
    Raltegravir (Arm A)     Placebo (Arm B)  
Number of Participants Analyzed  
[units: participants]
  20     23  
Change in CD8+/CD38+/HLA-DR+ Percent  
[units: % CD8 cells co-express CD38+ and HLA-DR+]
Median ( Inter-Quartile Range )
  -1  
  ( -2 to 2 )  
  0  
  ( -2 to 5 )  

No statistical analysis provided for Change in CD8+/CD38+/HLA-DR+ Percent



7.  Secondary:   Number of Participants Who Experienced Study Related Grade 2 or Higher Signs/Symptoms, Grade 3 or Higher Laboratory Abnormalities and Clinical Events From First Day of Treatment to Week 12   [ Time Frame: From first day of treatment to week 12 ]

Measure Type Secondary
Measure Title Number of Participants Who Experienced Study Related Grade 2 or Higher Signs/Symptoms, Grade 3 or Higher Laboratory Abnormalities and Clinical Events From First Day of Treatment to Week 12
Measure Description Participant who experienced at least one study related grade 2 or higher signs/symptoms, grade 3 or higher laboratory abnormalities and clinical events that are "possibly", "probably" or "definitely" related to study treatment. DAIDS Toxicity Grading Table (2004) was used for grading.
Time Frame From first day of treatment to week 12  
Safety Issue Yes  

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.
All participants on study treatment

Reporting Groups
  Description
Raltegravir (Arm A) 400 mg raltegravir (MK-0518) administered twice daily in addition to optimized background regimen (OBR) from entry to Week 12
Placebo (Arm B) Placebo administered twice daily in addition to OBR from entry until Week 12

Measured Values
    Raltegravir (Arm A)     Placebo (Arm B)  
Number of Participants Analyzed  
[units: participants]
  27     26  
Number of Participants Who Experienced Study Related Grade 2 or Higher Signs/Symptoms, Grade 3 or Higher Laboratory Abnormalities and Clinical Events From First Day of Treatment to Week 12  
[units: Participant]
  2     0  

No statistical analysis provided for Number of Participants Who Experienced Study Related Grade 2 or Higher Signs/Symptoms, Grade 3 or Higher Laboratory Abnormalities and Clinical Events From First Day of Treatment to Week 12



8.  Secondary:   Number of Participants Who Experienced Study Related Grade 2 or Higher Signs/Symptoms, Grade 3 or Higher Laboratory Abnormalities and Clinical Events From Week 12 to Week 24   [ Time Frame: From week 12 to week 24 ]

Measure Type Secondary
Measure Title Number of Participants Who Experienced Study Related Grade 2 or Higher Signs/Symptoms, Grade 3 or Higher Laboratory Abnormalities and Clinical Events From Week 12 to Week 24
Measure Description Participant who experienced at least one study related grade 2 or higher signs/symptoms, grade 3 or higher laboratory abnormalities and clinical events that are 'possibly', probably', or definitely' related to study treatment. DAIDS Toxicity Grading Table (2004) was used for grading.
Time Frame From week 12 to week 24  
Safety Issue Yes  

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.
No text entered.

Reporting Groups
  Description
Placebo (Arm A) Placebo administered twice daily in addition to optimized background regimen (OBR) from week 12 to week 24
Raltegravir (Arm B) 400 mg raltegravir (MK-0518) administered twice daily in addition to OBR from week 12 to week 24

Measured Values
    Placebo (Arm A)     Raltegravir (Arm B)  
Number of Participants Analyzed  
[units: participants]
  23     25  
Number of Participants Who Experienced Study Related Grade 2 or Higher Signs/Symptoms, Grade 3 or Higher Laboratory Abnormalities and Clinical Events From Week 12 to Week 24  
[units: participants]
  0     0  

No statistical analysis provided for Number of Participants Who Experienced Study Related Grade 2 or Higher Signs/Symptoms, Grade 3 or Higher Laboratory Abnormalities and Clinical Events From Week 12 to Week 24



9.  Secondary:   Number of Participants Who Discontinued Study Drug   [ Time Frame: From first day of treatment to week 12 ]

Measure Type Secondary
Measure Title Number of Participants Who Discontinued Study Drug
Measure Description Participants who discontinued randomized study treatment for any reason
Time Frame From first day of treatment to week 12  
Safety Issue No  

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.
All 53 participants

Reporting Groups
  Description
Raltegravir (Arm A) 400 mg raltegravir (MK-0518) administered twice daily in addition to optimized background regimen (OBR) from entry to Week 12
Placebo (Arm B) Placebo administered twice daily in addition to OBR from entry until Week 12

Measured Values
    Raltegravir (Arm A)     Placebo (Arm B)  
Number of Participants Analyzed  
[units: participants]
  27     26  
Number of Participants Who Discontinued Study Drug  
[units: Participant]
  4     1  

No statistical analysis provided for Number of Participants Who Discontinued Study Drug




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

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