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Effects of Switching Efavirenz to Raltegravir on Vascular Function and Bone Markers in HIV-infected Patients

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ClinicalTrials.gov Identifier: NCT01270802
Recruitment Status : Completed
First Posted : January 5, 2011
Results First Posted : October 24, 2013
Last Update Posted : December 18, 2013
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Samir Gupta, Indiana University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition HIV
Interventions Drug: Tenofovir/emtricitabine
Drug: Tenofovir/emtricitabine/efavirenz
Drug: Raltegravir
Enrollment 30

Recruitment Details Enrollment into this trial occurred between April 2011 and May 2012. Participants were recruited from the HIV outpatient clinics associated with the Indiana University Health medical system.
Pre-assignment Details Thirty-two persons screened for enrollment. Two of these failed screening (both for having screening HIV-1 RNA levels >50 copies/mL); the remaining 30 were equally randomized into the two study groups.
Arm/Group Title Continued Tenofovir/Emtricitabine/Efavirenz Switch to Tenofovir/Emtricitabine Plus Raltegravir
Hide Arm/Group Description Tenofovir/emtricitabine/efavirenz : Continued therapy with tenofovir/emtricitabine/efavirenz (as Atripla) one pill per day Tenofovir/emtricitabine/raltegravir : Tenofovir/emtricitabine/efavirenz (as Atripla one pill per day) will be switched to tenofovir/emtricitabine (as Truvada one pill per day) plus raltegravir (as Isentress) 400mg orally twice daily
Period Title: Overall Study
Started 15 15
Completed 13 14
Not Completed 2 1
Reason Not Completed
Withdrawal by Subject             1             0
Adverse Event             1             0
Lost to Follow-up             0             1
Arm/Group Title Continued Tenofovir/Emtricitabine/Efavirenz Switch to Tenofovir/Emtricitabine/Raltegravir Total
Hide Arm/Group Description Tenofovir/emtricitabine/efavirenz : Continued therapy with tenofovir/emtricitabine/efavirenz

Tenofovir/emtricitabine/efavirenz is switched to tenofovir/emtricitabine/raltegravir

Tenofovir/emtricitabine/raltegravir : Efavirenz will be switched to raltegravir 400mg orally twice daily while continuing tenofovir/emtricitabine

Total of all reporting groups
Overall Number of Baseline Participants 15 15 30
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants 15 participants 30 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
15
 100.0%
15
 100.0%
30
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 15 participants 15 participants 30 participants
38  (12) 39  (10.6) 39  (11)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants 15 participants 30 participants
Female
2
  13.3%
1
   6.7%
3
  10.0%
Male
13
  86.7%
14
  93.3%
27
  90.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 15 participants 15 participants 30 participants
15 15 30
1.Primary Outcome
Title Change in Flow-mediated Dilation (FMD) of the Brachial Artery
Hide Description Change in FMD is a measure of change in endothelial function
Time Frame Baseline and 24 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
In the Switch to tenofovir/emtricitabine plus raltegravir arm, two FMD measurements at 24 weeks were removed from the analysis due to poor quality imaging.
Arm/Group Title Continued Tenofovir/Emtricitabine/Efavirenz Switch to Tenofovir/Emtricitabine Plus Raltegravir
Hide Arm/Group Description:
Tenofovir/emtricitabine/efavirenz : Continued therapy with tenofovir/emtricitabine/efavirenz
Tenofovir/emtricitabine plus raltegravir 400mg orally twice daily
Overall Number of Participants Analyzed 13 12
Mean (Standard Deviation)
Unit of Measure: % change from baseline
-0.67  (3.35) -0.1  (3.26)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Continued Tenofovir/Emtricitabine/Efavirenz, Switch to Tenofovir/Emtricitabine Plus Raltegravir
Comments We assumed that the declines in FMD seen with TDF/FTC/EFV in our previous study would fully reverse. Thus, the clinically relevant effect size to be detected for FMD change was +3.12% (SD 4%) in those switching from EFV to RAL. Using a two-sample, independent, two-tailed t-test with 5% type I error and 20% type II error, a sample size of 13 per group would be needed to find a difference in FMD between groups. Allowing for a 10% dropout rate, we planned to recruit 15 subjects per group.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.67
Comments P-value was not adjusted for multiple comparisons; P<0.05 was considered statistically significant.
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.81
Confidence Interval (2-Sided) 95%
-0.75 to 2.37
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.76
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change in Serum Levels of Vitamin D
Hide Description Change in serum levels of 24-OH-vitamin D provide a measure of the amount of change in vitamin D in the body
Time Frame Baseline and 24 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Continued Tenofovir/Emtricitabine/Efavirenz Switch to Tenofovir/Emtricitabine Plus Raltegravir
Hide Arm/Group Description:
Tenofovir/emtricitabine/efavirenz : Continued therapy with tenofovir/emtricitabine/efavirenz
Tenofovir/emtricitabine/efavirenz will be switched to tenofovir/emtricitabine plus raltegravir 400mg orally twice daily
Overall Number of Participants Analyzed 13 14
Mean (Standard Deviation)
Unit of Measure: ng/mL
0.06  (0.23) 0.14  (0.25)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Continued Tenofovir/Emtricitabine/Efavirenz, Switch to Tenofovir/Emtricitabine Plus Raltegravir
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.40
Comments P-value was not adjusted for multiple comparisons. P<0.05 was considered statistically significant.
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.63
Confidence Interval (2-Sided) 95%
-13.04 to 9.77
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.52
Estimation Comments [Not Specified]
Time Frame 6 months
Adverse Event Reporting Description Laboratory toxicities were assessed at week 8 and week 24.
 
Arm/Group Title Continued Tenofovir/Emtricitabine/Efavirenz Switch to Tenofovir/Emtricitabine/Raltegravir
Hide Arm/Group Description Tenofovir/emtricitabine/efavirenz : Continued therapy with tenofovir/emtricitabine/efavirenz

Tenofovir/emtricitabine/efavirenz is switched to tenofovir/emtricitabine/raltegravir

Tenofovir/emtricitabine/raltegravir : Efavirenz will be switched to raltegravir 400mg orally twice daily while continuing tenofovir/emtricitabine

All-Cause Mortality
Continued Tenofovir/Emtricitabine/Efavirenz Switch to Tenofovir/Emtricitabine/Raltegravir
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Continued Tenofovir/Emtricitabine/Efavirenz Switch to Tenofovir/Emtricitabine/Raltegravir
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/15 (0.00%)      0/15 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Continued Tenofovir/Emtricitabine/Efavirenz Switch to Tenofovir/Emtricitabine/Raltegravir
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/15 (20.00%)      1/15 (6.67%)    
Blood and lymphatic system disorders     
Neutropenia   0/15 (0.00%)  0 1/15 (6.67%)  1
Endocrine disorders     
Impaired fasting glucose   1/15 (6.67%)  1 0/15 (0.00%)  0
Infections and infestations     
Virologic failure  [1]  1/15 (6.67%)  1 0/15 (0.00%)  0
Vascular disorders     
Diastolic hypertension   1/15 (6.67%)  1 0/15 (0.00%)  0
Indicates events were collected by systematic assessment
[1]
Confirmed HIV-1 RNA over 50 copies/mL
The study was open-label. Correction for multiple testing was not performed, so apparently significant results may be falsely positive.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Dr. Samir K. Gupta, Principal Investigator
Organization: Indiana University School of Medicine
Phone: 317-274-7926
Responsible Party: Samir Gupta, Indiana University
ClinicalTrials.gov Identifier: NCT01270802     History of Changes
Other Study ID Numbers: Merck 38258
First Submitted: January 4, 2011
First Posted: January 5, 2011
Results First Submitted: August 14, 2013
Results First Posted: October 24, 2013
Last Update Posted: December 18, 2013