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

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00549198
First received: October 24, 2007
Last updated: April 7, 2011
Last verified: April 2011
Results First Received: September 23, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety Study;   Intervention Model: Parallel Assignment;   Masking: 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
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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
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
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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
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  
Number of Participants  
[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  
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
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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 ]

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 ]

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 ]

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

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

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

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 ]

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 ]

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 ]

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 ]

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 ]

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 ]

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 ]

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 ]

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 ]

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 ]

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 ]

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 ]

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 ]

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 ]

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 ]
  Hide Outcome Measure 21

Measure Type Secondary
Measure Title 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
Measure Description BMD is a measure of the mineral content of bone in a particular skeletal area. DXA scans use low energy x-rays to measure the density of bones.
Time Frame Baseline, Week 96  
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.
ITT-E Population. Some participants had withdrawn by Week 96/did not have a DXA scan performed. DXA, dual energy x-ray absorptiometry.

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  
Number of Participants Analyzed  
[units: participants]
  59     79  
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  
[units: participants]
   
>=2%, spine, n=59, 79     21     39  
>=6%, spine, n=59, 79     3     8  
>=2%, hip, n=58, 76     33     52  
>=6%, hip, n=58, 76     1     13  

No statistical analysis provided for 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



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 ]

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 ]

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 ]

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

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

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

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 ]

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 ]

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 ]

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 ]

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 ]

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 ]

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 ]

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 ]

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 ]

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 ]

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 ]

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 ]

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

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

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

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 ]

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 ]

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 ]

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

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

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

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 ]

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 ]

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 ]

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 ]

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 ]

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 ]

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 ]

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 ]

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

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


  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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