ClinicalTrials.gov
ClinicalTrials.gov Menu

Metabolic Effects of Switching Kaletra to Boosted Reyataz

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00413153
Recruitment Status : Completed
First Posted : December 19, 2006
Results First Posted : March 3, 2010
Last Update Posted : March 9, 2010
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by:
Massachusetts General Hospital

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition HIV Infections
Interventions Drug: atazanavir/ritonavir
Drug: lopinavir/ritonavir
Enrollment 15

Recruitment Details 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 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.
Arm/Group Title Boosted Reyataz (ATV/r) Continue Kaletra (LPV/r)
Hide Arm/Group Description Boosted Reyataz (300mg atazanavir + 100mg ritonavir) Kaletra (pre-study dose)
Period Title: Overall Study
Started 7 8
Completed 5 7
Not Completed 2 1
Reason Not Completed
Withdrawal by Subject             1             1
Adverse Event             1             0
Arm/Group Title Boosted Reyataz (ATV/r) Continue Kaletra (LPV/r) Total
Hide Arm/Group Description Boosted Reyataz (300mg atazanavir + 100mg ritonavir) Kaletra (pre-study dose) Total of all reporting groups
Overall Number of Baseline Participants 7 8 15
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 8 participants 15 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
7
 100.0%
8
 100.0%
15
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 7 participants 8 participants 15 participants
46  (8) 50  (6) 48  (7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 8 participants 15 participants
Female
2
  28.6%
1
  12.5%
3
  20.0%
Male
5
  71.4%
7
  87.5%
12
  80.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 7 participants 8 participants 15 participants
7 8 15
1.Primary Outcome
Title Glucose Trafficking
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Only data from subjects with 0 and 6 month Positron Emission Tomography (PET) scans were analyzed.
Arm/Group Title Boosted Reyataz (ATV/r) Continue Kaletra (LPV/r)
Hide Arm/Group Description:
Boosted Reyataz (300mg atazanavir + 100mg ritonavir)
Kaletra (pre-study dose)
Overall Number of Participants Analyzed 5 6
Mean (Standard Deviation)
Unit of Measure: umol/kg/min
26.7  (8.1) 24.4  (17.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Boosted Reyataz (ATV/r), Continue Kaletra (LPV/r)
Comments 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).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.035
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
2.Secondary Outcome
Title Insulin Sensitivity
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Repeated measures analysis using all available data points for each participant
Arm/Group Title Boosted Reyataz (ATV/r) Continue Kaletra (LPV/r)
Hide Arm/Group Description:
Boosted Reyataz (300mg atazanavir + 100mg ritonavir)
Kaletra (pre-study dose)
Overall Number of Participants Analyzed 5 7
Mean (Standard Deviation)
Unit of Measure: umol/kg/min per uU/mL insulin
39.0  (17.7) 49.2  (22.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Boosted Reyataz (ATV/r), Continue Kaletra (LPV/r)
Comments 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)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.12
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
3.Secondary Outcome
Title Fasting Glucose
Hide Description 6 month mean and standard deviation for fasting glucose.
Time Frame 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Repeated measures analysis using all available data points for each participant
Arm/Group Title Boosted Reyataz (ATV/r) Continue Kaletra (LPV/r)
Hide Arm/Group Description:
Boosted Reyataz (300mg atazanavir + 100mg ritonavir)
Kaletra (pre-study dose)
Overall Number of Participants Analyzed 5 7
Mean (Standard Deviation)
Unit of Measure: mg/dL
84  (7) 90  (21)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Boosted Reyataz (ATV/r), Continue Kaletra (LPV/r)
Comments 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).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method Repeated Measures ANCOVA
Comments [Not Specified]
4.Secondary Outcome
Title Lipid Metabolism - Serum Triglyceride
Hide Description 6 month mean and standard deviation for serum triglyceride.
Time Frame 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Repeated measures analysis using all available data points for each participant
Arm/Group Title Boosted Reyataz (ATV/r) Continue Kaletra (LPV/r)
Hide Arm/Group Description:
Boosted Reyataz (300mg atazanavir + 100mg ritonavir)
Kaletra (pre-study dose)
Overall Number of Participants Analyzed 5 7
Mean (Standard Deviation)
Unit of Measure: mg/dL
147  (92) 209  (87)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Boosted Reyataz (ATV/r), Continue Kaletra (LPV/r)
Comments 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).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.02
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
5.Secondary Outcome
Title Body Composition - Visceral Adipose Tissue
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Data from participants with 0 & 6 month data analyzed.
Arm/Group Title Boosted Reyataz (ATV/r) Continue Kaletra (LPV/r)
Hide Arm/Group Description:
Boosted Reyataz (300mg atazanavir + 100mg ritonavir)
Kaletra (pre-study dose)
Overall Number of Participants Analyzed 5 7
Mean (Standard Deviation)
Unit of Measure: square centimeters
91  (34) 167  (61)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Boosted Reyataz (ATV/r), Continue Kaletra (LPV/r)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.047
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
6.Secondary Outcome
Title Immune Parameters -- CD4 Count
Hide Description 6 month mean and standard deviation for CD4+ count.
Time Frame 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Repeated measures analysis using all available data points for each participant
Arm/Group Title Boosted Reyataz (ATV/r) Continue Kaletra (LPV/r)
Hide Arm/Group Description:
Boosted Reyataz (300mg atazanavir + 100mg ritonavir)
Kaletra (pre-study dose)
Overall Number of Participants Analyzed 5 7
Mean (Standard Deviation)
Unit of Measure: cells/microL
432  (192) 688  (230)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Boosted Reyataz (ATV/r), Continue Kaletra (LPV/r)
Comments 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).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.72
Comments [Not Specified]
Method Repeated Measures ANCOVA
Comments [Not Specified]
7.Secondary Outcome
Title Liver Enzymes -- Aspartate Aminotransferase (AST)
Hide Description 6 month mean and standard deviation for AST.
Time Frame 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Repeated measures analysis using all available data points for each participant
Arm/Group Title Boosted Reyataz (ATV/r) Continue Kaletra (LPV/r)
Hide Arm/Group Description:
Boosted Reyataz (300mg atazanavir + 100mg ritonavir)
Kaletra (pre-study dose)
Overall Number of Participants Analyzed 5 7
Mean (Standard Deviation)
Unit of Measure: U/L
39  (29) 42  (29)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Boosted Reyataz (ATV/r), Continue Kaletra (LPV/r)
Comments 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).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.22
Comments [Not Specified]
Method Repeated Measures ANCOVA
Comments [Not Specified]
8.Secondary Outcome
Title Liver Enzymes -- Alanine Aminotransferase (ALT)
Hide Description 6 month mean and standard deviation for ALT.
Time Frame 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Repeated measures analysis using all available data points for each participant
Arm/Group Title Boosted Reyataz (ATV/r) Continue Kaletra (LPV/r)
Hide Arm/Group Description:
Boosted Reyataz (300mg atazanavir + 100mg ritonavir)
Kaletra (pre-study dose)
Overall Number of Participants Analyzed 5 7
Mean (Standard Deviation)
Unit of Measure: U/L
61  (29) 65  (34)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Boosted Reyataz (ATV/r), Continue Kaletra (LPV/r)
Comments 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).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method Repeated Measures Ancova
Comments [Not Specified]
9.Secondary Outcome
Title Total Bilirubin
Hide Description 6 month mean and standard deviation for total bilirubin.
Time Frame 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Repeated measures analysis using all available data points for each participant
Arm/Group Title Boosted Reyataz (ATV/r) Continue Kaletra (LPV/r)
Hide Arm/Group Description:
Boosted Reyataz (300mg atazanavir + 100mg ritonavir)
Kaletra (pre-study dose)
Overall Number of Participants Analyzed 5 7
Mean (Standard Deviation)
Unit of Measure: mg/dL
2.8  (2.7) 0.6  (0.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Boosted Reyataz (ATV/r), Continue Kaletra (LPV/r)
Comments 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).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method Repeated Measures ANCOVA
Comments [Not Specified]
Time Frame 6 month study period
Adverse Event Reporting Description All subjects had physical examinations and were queried about any adverse event at each study visit (baseline, 2 weeks, 1 month, 2 months, 4 months, and 6 months), and bilirubin, ALT, ALT, CD4+ count, and HIV ultrasensitive viral load were sent at all of these timepoints.
 
Arm/Group Title Boosted Reyataz (ATV/r) Continue Kaletra (LPV/r)
Hide Arm/Group Description Boosted Reyataz (300mg atazanavir + 100mg ritonavir) Kaletra (pre-study dose)
All-Cause Mortality
Boosted Reyataz (ATV/r) Continue Kaletra (LPV/r)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Boosted Reyataz (ATV/r) Continue Kaletra (LPV/r)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/7 (28.57%)      0/8 (0.00%)    
Gastrointestinal disorders     
Giardia Lamblia Infection  1 [1]  1/7 (14.29%)  1 0/8 (0.00%)  0
General disorders     
Mental Status Changes  1 [2]  1/7 (14.29%)  1 0/8 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
[1]
hospitalization required for Giardia lamblia infection
[2]
Mental status changes requiring hospitalization, found to be caused by combination of prescribed opiates
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Boosted Reyataz (ATV/r) Continue Kaletra (LPV/r)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/7 (85.71%)      1/8 (12.50%)    
Gastrointestinal disorders     
hyperbilirubinemia  1  6/7 (85.71%)  0/8 (0.00%) 
transaminitis  1 [1]  1/7 (14.29%)  0/8 (0.00%) 
Infections and infestations     
HIV RNA Copy Number Increased  1  1/7 (14.29%)  0/8 (0.00%) 
Metabolism and nutrition disorders     
Type 2 Diabetes Mellitus  1  0/7 (0.00%)  1/8 (12.50%) 
Skin and subcutaneous tissue disorders     
cellulitis  1  1/7 (14.29%)  0/8 (0.00%) 
rash  1  1/7 (14.29%)  0/8 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
[1]
ALT and/or AST elevated to any degree above the upper limit of normal.
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.
Results Point of Contact
Name/Title: Steven K. Grinspoon, MD
Organization: Massachusetts General Hospital
Phone: 617-724-9109
Responsible Party: Steven K. Grinspoon, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00413153     History of Changes
Other Study ID Numbers: 2005-P-002239
First Submitted: December 15, 2006
First Posted: December 19, 2006
Results First Submitted: November 4, 2009
Results First Posted: March 3, 2010
Last Update Posted: March 9, 2010