Metabolic Effects of Switching Kaletra to Boosted Reyataz

This study has been completed.
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by:
Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00413153
First received: December 15, 2006
Last updated: March 5, 2010
Last verified: March 2010
Results First Received: November 4, 2009  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: HIV Infections
Interventions: Drug: atazanavir/ritonavir
Drug: lopinavir/ritonavir

  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 were recruited through information given to HIV-care providers, postings in HIV-community organizations, newspaper advertisements, and the Massachusetts General Hospital research patient data registry. Recruitment began in March, 2006, and continued through May, 2008.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
After screening visit to determine eligibility, subjects were asked to continue their current antiretroviral medications until the baseline visit, immediately after which they were randomized to continue lopinavir/ritonavir or switch to atazanavir/ritonavir.

Reporting Groups
  Description
Boosted Reyataz (ATV/r) Boosted Reyataz (300mg atazanavir + 100mg ritonavir)
Continue Kaletra (LPV/r) Kaletra (pre-study dose)

Participant Flow:   Overall Study
    Boosted Reyataz (ATV/r)     Continue Kaletra (LPV/r)  
STARTED     7     8  
COMPLETED     5     7  
NOT COMPLETED     2     1  
Withdrawal by Subject                 1                 1  
Adverse Event                 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
Boosted Reyataz (ATV/r) Boosted Reyataz (300mg atazanavir + 100mg ritonavir)
Continue Kaletra (LPV/r) Kaletra (pre-study dose)
Total Total of all reporting groups

Baseline Measures
    Boosted Reyataz (ATV/r)     Continue Kaletra (LPV/r)     Total  
Number of Participants  
[units: participants]
  7     8     15  
Age  
[units: participants]
     
<=18 years     0     0     0  
Between 18 and 65 years     7     8     15  
>=65 years     0     0     0  
Age  
[units: years]
Mean ± Standard Deviation
  46  ± 8     50  ± 6     48  ± 7  
Gender  
[units: participants]
     
Female     2     1     3  
Male     5     7     12  
Region of Enrollment  
[units: participants]
     
United States     7     8     15  



  Outcome Measures
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1.  Primary:   Glucose Trafficking   [ Time Frame: 6 months ]

Measure Type Primary
Measure Title Glucose Trafficking
Measure Description 6 month mean and standard deviation for glucose uptake into anterior thigh muscle as measured by FDG/PET scanning during euglycemic hyperinsulinemic clamp. During the hyperinsulinemic conditions of the clamp, glucose and 18-FDG [labeled glucose] are taken up by muscle. The quantity of 18-FDG taken up is measured by the PET scan. Although there are no well-accepted norms for this measurement, a higher value indicates that more glucose is being taken up by (or "trafficked to") muscle. Increased uptake of glucose indicates increased muscle insulin sensitivity.
Time Frame 6 months  
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.
Only data from subjects with 0 and 6 month Positron Emission Tomography (PET) scans were analyzed.

Reporting Groups
  Description
Boosted Reyataz (ATV/r) Boosted Reyataz (300mg atazanavir + 100mg ritonavir)
Continue Kaletra (LPV/r) Kaletra (pre-study dose)

Measured Values
    Boosted Reyataz (ATV/r)     Continue Kaletra (LPV/r)  
Number of Participants Analyzed  
[units: participants]
  5     6  
Glucose Trafficking  
[units: umol/kg/min]
Mean ± Standard Deviation
  26.7  ± 8.1     24.4  ± 17.7  


Statistical Analysis 1 for Glucose Trafficking
Groups [1] All groups
Method [2] t-test, 2 sided
P Value [3] 0.035
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Initial samples size of N=16 calculated to provide 80% power to detect a 30% change in muscle glucose uptake between groups. Student's t-test used to compare change from baseline and determine treatment effect (net difference over time between the ATV/r vs. LPV/r groups).
[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:
  No text entered.



2.  Secondary:   Insulin Sensitivity   [ Time Frame: 6 months ]

Measure Type Secondary
Measure Title Insulin Sensitivity
Measure Description 6 month mean and standard deviation for insulin-stimulated glucose uptake (M) per unit insulin at 120 minutes as measured by euglycemic hyperinsulinemic clamp.
Time Frame 6 months  
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.
Repeated measures analysis using all available data points for each participant

Reporting Groups
  Description
Boosted Reyataz (ATV/r) Boosted Reyataz (300mg atazanavir + 100mg ritonavir)
Continue Kaletra (LPV/r) Kaletra (pre-study dose)

Measured Values
    Boosted Reyataz (ATV/r)     Continue Kaletra (LPV/r)  
Number of Participants Analyzed  
[units: participants]
  5     7  
Insulin Sensitivity  
[units: umol/kg/min per uU/mL insulin]
Mean ± Standard Deviation
  39.0  ± 17.7     49.2  ± 22.5  


Statistical Analysis 1 for Insulin Sensitivity
Groups [1] All groups
Method [2] Repeated measures ANCOVA
P Value [3] 0.12
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Repeated measures ANCOVA, controlling for baseline values, used to assess treatment effect of the randomization over 6 months (net difference over time between ATV/r vs. LPV/r)
[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:
  No text entered.



3.  Secondary:   Fasting Glucose   [ Time Frame: 6 months ]

Measure Type Secondary
Measure Title Fasting Glucose
Measure Description 6 month mean and standard deviation for fasting glucose.
Time Frame 6 months  
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.
Repeated measures analysis using all available data points for each participant

Reporting Groups
  Description
Boosted Reyataz (ATV/r) Boosted Reyataz (300mg atazanavir + 100mg ritonavir)
Continue Kaletra (LPV/r) Kaletra (pre-study dose)

Measured Values
    Boosted Reyataz (ATV/r)     Continue Kaletra (LPV/r)  
Number of Participants Analyzed  
[units: participants]
  5     7  
Fasting Glucose  
[units: mg/dL]
Mean ± Standard Deviation
  84  ± 7     90  ± 21  


Statistical Analysis 1 for Fasting Glucose
Groups [1] All groups
Method [2] Repeated Measures ANCOVA
P Value [3] 0.002
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Repeated measures ANCOVA, controlling for baseline values, used to assess treatment effect of the randomization over 6 months (net difference over time between ATV/r vs.LPV/r).
[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:
  No text entered.



4.  Secondary:   Lipid Metabolism - Serum Triglyceride   [ Time Frame: 6 months ]

Measure Type Secondary
Measure Title Lipid Metabolism - Serum Triglyceride
Measure Description 6 month mean and standard deviation for serum triglyceride.
Time Frame 6 months  
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.
Repeated measures analysis using all available data points for each participant

Reporting Groups
  Description
Boosted Reyataz (ATV/r) Boosted Reyataz (300mg atazanavir + 100mg ritonavir)
Continue Kaletra (LPV/r) Kaletra (pre-study dose)

Measured Values
    Boosted Reyataz (ATV/r)     Continue Kaletra (LPV/r)  
Number of Participants Analyzed  
[units: participants]
  5     7  
Lipid Metabolism - Serum Triglyceride  
[units: mg/dL]
Mean ± Standard Deviation
  147  ± 92     209  ± 87  


Statistical Analysis 1 for Lipid Metabolism - Serum Triglyceride
Groups [1] All groups
Method [2] Repeated measures ANCOVA
P Value [3] 0.02
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Repeated measures ANCOVA, controlling for baseline values, used to assess treatment effect of the randomization over 6 months (net difference over time between ATV/r vs.LPV/r).
[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:
  No text entered.



5.  Secondary:   Body Composition - Visceral Adipose Tissue   [ Time Frame: 6 months ]

Measure Type Secondary
Measure Title Body Composition - Visceral Adipose Tissue
Measure Description 6 month mean and standard deviation for visceral adipose tissue (VAT) as measured by single slice computed tomography (CT) scan at the L4 pedicle (pedicle of 4th lumbar vertebra).
Time Frame 6 months  
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.
Data from participants with 0 & 6 month data analyzed.

Reporting Groups
  Description
Boosted Reyataz (ATV/r) Boosted Reyataz (300mg atazanavir + 100mg ritonavir)
Continue Kaletra (LPV/r) Kaletra (pre-study dose)

Measured Values
    Boosted Reyataz (ATV/r)     Continue Kaletra (LPV/r)  
Number of Participants Analyzed  
[units: participants]
  5     7  
Body Composition - Visceral Adipose Tissue  
[units: square centimeters]
Mean ± Standard Deviation
  91  ± 34     167  ± 61  


Statistical Analysis 1 for Body Composition - Visceral Adipose Tissue
Groups [1] All groups
Method [2] t-test, 2 sided
P Value [3] 0.047
[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:
  No text entered.



6.  Secondary:   Immune Parameters -- CD4 Count   [ Time Frame: 6 months ]

Measure Type Secondary
Measure Title Immune Parameters -- CD4 Count
Measure Description 6 month mean and standard deviation for CD4+ count.
Time Frame 6 months  
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.
Repeated measures analysis using all available data points for each participant

Reporting Groups
  Description
Boosted Reyataz (ATV/r) Boosted Reyataz (300mg atazanavir + 100mg ritonavir)
Continue Kaletra (LPV/r) Kaletra (pre-study dose)

Measured Values
    Boosted Reyataz (ATV/r)     Continue Kaletra (LPV/r)  
Number of Participants Analyzed  
[units: participants]
  5     7  
Immune Parameters -- CD4 Count  
[units: cells/microL]
Mean ± Standard Deviation
  432  ± 192     688  ± 230  


Statistical Analysis 1 for Immune Parameters -- CD4 Count
Groups [1] All groups
Method [2] Repeated Measures ANCOVA
P Value [3] 0.72
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Repeated measures ANCOVA, controlling for baseline values, used to assess treatment effect of the randomization over 6 months (net difference over time between ATV/r vs.LPV/r).
[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:
  No text entered.



7.  Secondary:   Liver Enzymes -- Aspartate Aminotransferase (AST)   [ Time Frame: 6 months ]

Measure Type Secondary
Measure Title Liver Enzymes -- Aspartate Aminotransferase (AST)
Measure Description 6 month mean and standard deviation for AST.
Time Frame 6 months  
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.
Repeated measures analysis using all available data points for each participant

Reporting Groups
  Description
Boosted Reyataz (ATV/r) Boosted Reyataz (300mg atazanavir + 100mg ritonavir)
Continue Kaletra (LPV/r) Kaletra (pre-study dose)

Measured Values
    Boosted Reyataz (ATV/r)     Continue Kaletra (LPV/r)  
Number of Participants Analyzed  
[units: participants]
  5     7  
Liver Enzymes -- Aspartate Aminotransferase (AST)  
[units: U/L]
Mean ± Standard Deviation
  39  ± 29     42  ± 29  


Statistical Analysis 1 for Liver Enzymes -- Aspartate Aminotransferase (AST)
Groups [1] All groups
Method [2] Repeated Measures ANCOVA
P Value [3] 0.22
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Repeated measures ANCOVA, controlling for baseline values, used to assess treatment effect of the randomization over 6 months (net difference over time between ATV/r vs.LPV/r).
[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:
  No text entered.



8.  Secondary:   Liver Enzymes -- Alanine Aminotransferase (ALT)   [ Time Frame: 6 months ]

Measure Type Secondary
Measure Title Liver Enzymes -- Alanine Aminotransferase (ALT)
Measure Description 6 month mean and standard deviation for ALT.
Time Frame 6 months  
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.
Repeated measures analysis using all available data points for each participant

Reporting Groups
  Description
Boosted Reyataz (ATV/r) Boosted Reyataz (300mg atazanavir + 100mg ritonavir)
Continue Kaletra (LPV/r) Kaletra (pre-study dose)

Measured Values
    Boosted Reyataz (ATV/r)     Continue Kaletra (LPV/r)  
Number of Participants Analyzed  
[units: participants]
  5     7  
Liver Enzymes -- Alanine Aminotransferase (ALT)  
[units: U/L]
Mean ± Standard Deviation
  61  ± 29     65  ± 34  


Statistical Analysis 1 for Liver Enzymes -- Alanine Aminotransferase (ALT)
Groups [1] All groups
Method [2] Repeated Measures Ancova
P Value [3] 0.004
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Repeated measures ANCOVA, controlling for baseline values, used to assess treatment effect of the randomization over 6 months (net difference over time between ATV/r vs.LPV/r).
[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:
  No text entered.



9.  Secondary:   Total Bilirubin   [ Time Frame: 6 months ]

Measure Type Secondary
Measure Title Total Bilirubin
Measure Description 6 month mean and standard deviation for total bilirubin.
Time Frame 6 months  
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.
Repeated measures analysis using all available data points for each participant

Reporting Groups
  Description
Boosted Reyataz (ATV/r) Boosted Reyataz (300mg atazanavir + 100mg ritonavir)
Continue Kaletra (LPV/r) Kaletra (pre-study dose)

Measured Values
    Boosted Reyataz (ATV/r)     Continue Kaletra (LPV/r)  
Number of Participants Analyzed  
[units: participants]
  5     7  
Total Bilirubin  
[units: mg/dL]
Mean ± Standard Deviation
  2.8  ± 2.7     0.6  ± 0.3  


Statistical Analysis 1 for Total Bilirubin
Groups [1] All groups
Method [2] Repeated Measures ANCOVA
P Value [3] 0.0002
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Repeated measures ANCOVA, controlling for baseline values, used to assess treatment effect of the randomization over 6 months (net difference over time between ATV/r vs.LPV/r).
[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:
  No text entered.




  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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