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KIVEXA Vs TRUVADA, Both Administered With Efavirenz, In ART-Naive Subjects (ASSERT)

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ClinicalTrials.gov Identifier: NCT00549198
Recruitment Status : Completed
First Posted : October 25, 2007
Results First Posted : October 15, 2010
Last Update Posted : April 12, 2011
Sponsor:
Information provided by:
GlaxoSmithKline

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions: Infection, Human Immunodeficiency Virus I
HIV Infection
Interventions: Drug: Abacavir/lamivudine and efavirenz
Drug: Tenofovir/Emtricitabine and efavirenz

  Participant Flow

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
ABC/3TC FDC Abacavir (ABC) 600 mg/lamivudine (3TC) 300 mg fixed dose combination (FDC) once daily (QD) plus 600 mg efavirenz QD
TDF/FTC FDC Tenofovir (TDF) 300 mg/emtricitabine (FTC) 200 mg FDC once daily (QD) plus 600 mg efavirenz QD

Participant Flow:   Overall Study
    ABC/3TC FDC   TDF/FTC FDC
STARTED   195 [1]   197 [2] 
COMPLETED   115   134 
NOT COMPLETED   80   63 
Adverse Event                28                26 
Insufficient Viral Load Response                4                2 
Protocol-defined Virological Failure                7                0 
Non-compliance                2                4 
Lost to Follow-up                7                8 
Treatment Eligibility Criteria Not Met                3                0 
Protocol Violation                7                2 
Investigator Decision                4                3 
Withdrawal by Subject                7                7 
Disease Progression                1                0 
Participant Moved                2                0 
Participant not able to perform Week 96                1                0 
Participant moved.Week 96 visit, no scan                1                0 
Prohibited Medication                1                2 
Participant planning pregnancy                1                0 
Participant overweight, no scan possible                1                0 
No scan facilities                0                2 
Pregnancy                0                3 
Not Exposed to Study Drug                3                4 
[1] Three participants were randomized but were not exposed to study drug (ABC/3TC).
[2] Four participants were randomized but were not exposed to study drug (TDF/FTC).



  Baseline Characteristics

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
ABC/3TC FDC Abacavir (ABC) 600 mg/lamivudine (3TC) 300 mg fixed dose combination (FDC) once daily (QD) plus 600 mg efavirenz QD
TDF/FTC FDC Tenofovir (TDF) 300 mg/emtricitabine (FTC) 200 mg FDC once daily (QD) plus 600 mg efavirenz QD
Total Total of all reporting groups

Baseline Measures
   ABC/3TC FDC   TDF/FTC FDC   Total 
Overall Participants Analyzed 
[Units: Participants]
 		 192   193   385 
Age [1] 
[Units: Years]
Median (Full Range) 		 38.0 
 (19 to 70)  		 36.0 
 (18 to 66)  		 37.0 
 (18 to 70) 
Gender [1] 
[Units: Participants]
 		     
Female   33   40   73 
Male   159   153   312 
[1] The Intent-to-Treat (ITT)-Exposed (E) Population, comprised of all randomized participants who received at least one dose of study medication, was used for all baseline characteristics.
Race/Ethnicity, Customized [1] 
[Units: Participants]
 		     
African American/African Heritage   26   30   56 
American Indian or Alaska Native   11   7   18 
Asian   2   5   7 
White   153   151   304 
[1] The Intent-to-Treat (ITT)-Exposed (E) Population, comprised of all randomized participants who received at least one dose of study medication, was used for all baseline characteristics.


  Outcome Measures

1.  Primary:   Mean Change From Baseline in Estimated Glomerular Filtration Rate (GFR), Calculated by Modification of Diet in Renal Disease (MDRD) Equation, at Week 48   [ Time Frame: Baseline, Week 48 ]
  Show Outcome Measure 1

2.  Secondary:   Mean Change From Baseline in Estimated Glomerular Filtration Rate (GFR), Calculated by Modification of Diet in Renal Disease (MDRD) Equation, at Week 24   [ Time Frame: Baseline, Week 24 ]
  Show Outcome Measure 2

3.  Secondary:   Mean Change From Baseline in Estimated Glomerular Filtration Rate (GFR), Calculated by Modification of Diet in Renal Disease (MDRD) Equation, at Week 96   [ Time Frame: Baseline, Week 96 ]
  Hide Outcome Measure 3

Measure Type Secondary
Measure Title Mean Change From Baseline in Estimated Glomerular Filtration Rate (GFR), Calculated by Modification of Diet in Renal Disease (MDRD) Equation, at Week 96
Measure Description Change from baseline was calculated as the Week 96 value minus the baseline value. GFR is a measure of the rate at which blood is filtered by the kidney. MDRD is an equation (calculation) used to estimate GFR in participants with impaired renal function based on serum creatinine, age, race, and gender. GFR (mL/min/1.73 m^2) = 175 * (Scr)^-1.154 * (Age)^-0.203 * (0.742 if female) * (1.212 if African American) (conventional units). mL, milliliters; min, minute; m^s, meters squared; Scr, serum creatinine.
Time Frame Baseline, Week 96  

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.
ITT-E Population

Reporting Groups
  Description
ABC/3TC FDC Abacavir (ABC) 600 mg/lamivudine (3TC) 300 mg fixed dose combination (FDC) once daily (QD) plus 600 mg efavirenz QD
TDF/FTC FDC Tenofovir (TDF) 300 mg/emtricitabine (FTC) 200 mg FDC once daily (QD) plus 600 mg efavirenz QD

Measured Values
   ABC/3TC FDC   TDF/FTC FDC 
Participants Analyzed   192   193 
Mean Change From Baseline in Estimated Glomerular Filtration Rate (GFR), Calculated by Modification of Diet in Renal Disease (MDRD) Equation, at Week 96 
[Units: mL/min/1.73m^2]
Mean (Standard Error) 		 1.48  (1.022)   -1.15  (0.944) 


Statistical Analysis 1 for Mean Change From Baseline in Estimated Glomerular Filtration Rate (GFR), Calculated by Modification of Diet in Renal Disease (MDRD) Equation, at Week 96
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.060
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  The correlation matrix for within-subject errors is unstructured.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  The model includes the following covariates: treatment, visit, baseline GFR by MDRD, baseline BMI, race group, treatment*visit, baseline GFR by MDRD*visit and baseline BMI*visit.



4.  Secondary:   Mean Change From Baseline in Estimated GFR, Calculated by Cockcroft-Gault Equation, at Week 24   [ Time Frame: Baseline, Week 24 ]
  Show Outcome Measure 4

5.  Secondary:   Mean Change From Baseline in Estimated GFR, Calculated by Cockcroft-Gault Equation, at Week 48   [ Time Frame: Baseline, Week 48 ]
  Show Outcome Measure 5

6.  Secondary:   Mean Change From Baseline in Estimated GFR, Calculated by Cockcroft-Gault Equation, at Week 96   [ Time Frame: Baseline, Week 96 ]
  Show Outcome Measure 6

7.  Secondary:   Number of Participants With Decline From Baseline in Estimated GFR, Calculated by MDRD and Cockcroft-Gault Equations, of >=10 mL/Min/1.73 m^2 (mL/Min for Cockcroft-Gault), >=20 mL/Min/1.72 m^2, >=10%, and >=20% at Week 24   [ Time Frame: Baseline, Week 24 ]
  Show Outcome Measure 7

8.  Secondary:   Number of Participants With Decline From Baseline in Estimated GFR, Calculated by MDRD and Cockcroft-Gault Equations, of >=10 mL/Min/1.73m^2 (mL/Min for Cockcroft-Gault), >=20 mL/Min/1.72m^2, >=10%, and >=20% at Week 48   [ Time Frame: Baseline, Week 48 ]
  Show Outcome Measure 8

9.  Secondary:   Number of Participants With Decline From Baseline in Estimated GFR, Calculated by MDRD and Cockcroft-Gault Equations, of >=10 mL/Min/1.73m^2 (mL/Min for Cockcroft-Gault), >=20 mL/Min/1.72m^2, >=10%, and >=20% at Week 96   [ Time Frame: Baseline, Week 96 ]
  Show Outcome Measure 9

10.  Secondary:   Number of Participants With National Kidney Foundation Chronic Kidney Disease Stage 1, 2, 3, 4, or 5 Categories of Renal Function at Week 24   [ Time Frame: Baseline, Week 24 ]
  Show Outcome Measure 10

11.  Secondary:   Number of Participants With National Kidney Foundation Chronic Kidney Disease Stage 1, 2, 3, 4, or 5 Categories of Renal Function at Week 48   [ Time Frame: Baseline, Week 48 ]
  Show Outcome Measure 11

12.  Secondary:   Number of Participants With National Kidney Foundation Chronic Kidney Disease Stage 1, 2, 3, 4, or 5 Categories of Renal Function at Week 96   [ Time Frame: Baseline, Week 96 ]
  Show Outcome Measure 12

13.  Secondary:   Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD), Measured by Dual-energy X-ray Absorptiometry (DXA), at Week 24   [ Time Frame: Baseline, Week 24 ]
  Show Outcome Measure 13

14.  Secondary:   Percent Change From Baseline in Hip Bone Mineral Density (BMD), Measured by Dual-energy X-ray Absorptiometry (DXA), at Week 24   [ Time Frame: Baseline, Week 24 ]
  Show Outcome Measure 14

15.  Secondary:   Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD), Measured by Dual-energy X-ray Absorptiometry (DXA), at Week 48   [ Time Frame: Baseline, Week 48 ]
  Show Outcome Measure 15

16.  Secondary:   Percent Change From Baseline in Hip Bone Mineral Density (BMD), Measured by Dual-energy X-ray Absorptiometry (DXA), at Week 48   [ Time Frame: Baseline, Week 48 ]
  Show Outcome Measure 16

17.  Secondary:   Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD), Measured by Dual-energy X-ray Absorptiometry (DXA), at Week 96   [ Time Frame: Baseline, Week 96 ]
  Show Outcome Measure 17

18.  Secondary:   Percent Change From Baseline in Hip Bone Mineral Density (BMD), Measured by Dual-energy X-ray Absorptiometry (DXA), at Week 96   [ Time Frame: Baseline, Week 96 ]
  Show Outcome Measure 18

19.  Secondary:   Number of Participants With a Decline From Baseline in Lumbar Spine and Hip Bone Mineral Density (BMD) >=2.0% and >=6.0% at Week 24   [ Time Frame: Baseline, Week 24 ]
  Show Outcome Measure 19

20.  Secondary:   Number of Participants With a Decline From Baseline in Lumbar Spine and Hip Bone Mineral Density (BMD) >=2.0% and >=6.0% at Week 48   [ Time Frame: Baseline, Week 48 ]
  Show Outcome Measure 20

21.  Secondary:   Number of Participants With a Decline From Baseline in Lumbar Spine and Hip Bone Mineral Density (BMD) >=2.0% and >=6.0% at Week 96   [ Time Frame: Baseline, Week 96 ]
  Show Outcome Measure 21

22.  Secondary:   Number of Participants Meeting World Health Organization (WHO) Criteria for Osteopenia (T-score of -2.5 to -1.0) and Osteoporosis (T-score of <-2.5) at Week 24   [ Time Frame: Week 24 ]
  Show Outcome Measure 22

23.  Secondary:   Number of Participants Meeting World Health Organization (WHO) Criteria for Osteopenia (T-score of -2.5 to -1.0) and Osteoporosis (T-score of <-2.5) at Week 48   [ Time Frame: Week 48 ]
  Show Outcome Measure 23

24.  Secondary:   Number of Participants Meeting World Health Organization (WHO) Criteria for Osteopenia (T-score of -2.5 to -1.0) and Osteoporosis (T-score of <-2.5) at Week 96   [ Time Frame: Week 96 ]
  Show Outcome Measure 24

25.  Secondary:   Number of Participants Experiencing an Adverse Event (AE) Leading to Discontinuation by Week 24   [ Time Frame: Baseline to Week 24 ]
  Show Outcome Measure 25

26.  Secondary:   Number of Participants Experiencing an Adverse Event (AE) Leading to Discontinuation by Week 48   [ Time Frame: Baseline to Week 48 ]
  Show Outcome Measure 26

27.  Secondary:   Number of Participants Experiencing an Adverse Event (AE) Leading to Discontinuation by Week 96   [ Time Frame: Baseline to Week 96 ]
  Show Outcome Measure 27

28.  Secondary:   Number of Participants With the Indicated Change From Baseline in National Cholesterol Education Program (NCEP) Thresholds for Fasting Total Cholesterol at Week 24   [ Time Frame: Baseline, Week 24 ]
  Show Outcome Measure 28

29.  Secondary:   Number of Participants With the Indicated Change From Baseline in National Cholesterol Education Program (NCEP) Thresholds for Fasting Total Cholesterol at Week 48   [ Time Frame: Baseline, Week 48 ]
  Show Outcome Measure 29

30.  Secondary:   Number of Participants With the Indicated Change From Baseline in National Cholesterol Education Program (NCEP) Thresholds for Fasting Total Cholesterol at Week 96   [ Time Frame: Baseline, Week 96 ]
  Show Outcome Measure 30

31.  Secondary:   Number of Participants With the Indicated Change From Baseline in National Cholesterol Education Program (NCEP) Thresholds for Low-density Lipoprotein (LDL) at Week 24   [ Time Frame: Baseline, Week 24 ]
  Show Outcome Measure 31

32.  Secondary:   Number of Participants With the Indicated Change From Baseline in National Cholesterol Education Program (NCEP) Thresholds for Low-density Lipoprotein (LDL) at Week 48   [ Time Frame: Baseline, Week 48 ]
  Show Outcome Measure 32

33.  Secondary:   Number of Participants With the Indicated Change From Baseline in National Cholesterol Education Program (NCEP) Thresholds for Low-density Lipoprotein (LDL) at Week 96   [ Time Frame: Baseline, Week 96 ]
  Show Outcome Measure 33

34.  Secondary:   Number of Participants With the Indicated Change From Baseline in National Cholesterol Education Program (NCEP) Thresholds for Fasting High-density Lipoprotein (HDL) at Week 24   [ Time Frame: Baseline, Week 24 ]
  Show Outcome Measure 34

35.  Secondary:   Number of Participants With the Indicated Change From Baseline in National Cholesterol Education Program (NCEP) Thresholds for Fasting High-density Lipoprotein (HDL) at Week 48   [ Time Frame: Baseline, Week 48 ]
  Show Outcome Measure 35

36.  Secondary:   Number of Participants With the Indicated Change From Baseline in National Cholesterol Education Program (NCEP) Thresholds for Fasting High-density Lipoprotein (HDL) at Week 96   [ Time Frame: Baseline, Week 96 ]
  Show Outcome Measure 36

37.  Secondary:   Number of Participants With the Indicated Change From Baseline in National Cholesterol Education Program (NCEP) Thresholds for Fasting Triglycerides at Week 24   [ Time Frame: Baseline, Week 24 ]
  Show Outcome Measure 37

38.  Secondary:   Number of Participants With the Indicated Change From Baseline in National Cholesterol Education Program (NCEP) Thresholds for Fasting Triglycerides at Week 48   [ Time Frame: Baseline, Week 48 ]
  Show Outcome Measure 38

39.  Secondary:   Number of Participants With the Indicated Change From Baseline in National Cholesterol Education Program (NCEP) Thresholds for Fasting Triglycerides at Week 96   [ Time Frame: Baseline, Week 96 ]
  Show Outcome Measure 39

40.  Secondary:   Number of Participants With the Indicated Treatment-emergent Division of AIDS (DAIDS) Toxicities at Week 24   [ Time Frame: Week 24 ]
  Show Outcome Measure 40

41.  Secondary:   Number of Participants With the Indicated Treatment-emergent Division of AIDS (DAIDS) Toxicities at Week 48   [ Time Frame: Week 48 ]
  Show Outcome Measure 41

42.  Secondary:   Number of Participants With the Indicated Treatment-emergent Division of AIDS (DAIDS) Toxicities at Week 96   [ Time Frame: Week 96 ]
  Show Outcome Measure 42

43.  Secondary:   Number of Participants With HIV-1 RNA <50 Copies/Milliliter (c/mL) and 400 c/mL at Week 24   [ Time Frame: Week 24 ]
  Show Outcome Measure 43

44.  Secondary:   Number of Participants With HIV-1 RNA <50 Copies/Milliliter (c/mL) and 400 c/mL at Week 48   [ Time Frame: Week 48 ]
  Show Outcome Measure 44

45.  Secondary:   Number of Participants With HIV-1 RNA <50 Copies/Milliliter (c/mL) and 400 c/mL at Week 96   [ Time Frame: Week 96 ]
  Show Outcome Measure 45

46.  Secondary:   Change From Baseline in Cluster Difference 4 (CD4+) Cell Count at Week 24   [ Time Frame: Baseline, Week 24 ]
  Show Outcome Measure 46

47.  Secondary:   Change From Baseline in Cluster Difference 4 (CD4+) Cell Count at Week 48   [ Time Frame: Baseline, Week 48 ]
  Show Outcome Measure 47

48.  Secondary:   Change From Baseline in Cluster Difference 4 (CD4+) Cell Count at Week 96   [ Time Frame: Baseline, Week 96 ]
  Show Outcome Measure 48

49.  Secondary:   Number of Participants Classified as Protocol-defined Failures With Treatment-emergent Resistance to Study Drug in the Indicated Viruses at Week 96   [ Time Frame: Week 96 ]
  Show Outcome Measure 49

50.  Secondary:   Number of Participants Who Indicated "Yes" or "No" to the Question of Whether Unplanned Healthcare Resources Were Utilized   [ Time Frame: Baseline to Week 96 ]
  Show Outcome Measure 50

51.  Other Pre-specified:   Exploratory Analysis of Change From Baseline in Albumin as a Ratio to Urine Creatinine at Week 96   [ Time Frame: Baseline, Week 96 ]
  Show Outcome Measure 51

52.  Other Pre-specified:   Exploratory Analysis of Change From Baseline in Beta 2 Microglobulin (B2M) as a Ratio to Urine Creatinine at Week 96   [ Time Frame: Baseline, Week 96 ]
  Show Outcome Measure 52

53.  Other Pre-specified:   Exploratory Analysis of Change From Baseline in N-acetyl-B-glucosaminidase (NAG) as a Ratio to Urine Creatinine at Week 96   [ Time Frame: Baseline, Week 96 ]
  Show Outcome Measure 53

54.  Other Pre-specified:   Exploratory Analysis of Change From Baseline in Retinol Binding Protein (RBP) as a Ratio to Urine Creatinine at Week 96   [ Time Frame: Baseline, Week 96 ]
  Show Outcome Measure 54

55.  Other Pre-specified:   Exploratory Analysis of Change From Baseline in Procollagen Type 1 Amino-terminal Propeptide (P1NP) at Week 96   [ Time Frame: Baseline, Week 96 ]
  Show Outcome Measure 55

56.  Other Pre-specified:   Exploratory Analysis of Change From Baseline in Type 1 Collagen Cross-linked C-telopeptide at Week 96   [ Time Frame: Baseline, Week 96 ]
  Show Outcome Measure 56

57.  Other Pre-specified:   Exploratory Analysis of Change From Baseline in Osteocalcin at Week 96   [ Time Frame: Baseline, Week 96 ]
  Show Outcome Measure 57

58.  Other Pre-specified:   Exploratory Analysis of Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) at Week 96   [ Time Frame: Baseline, Week 96 ]
  Show Outcome Measure 58


  Serious Adverse Events


  Other Adverse Events


  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
No text entered.


  More Information