A Randomised, Open-label Trial to Assess the Safety and Efficacy of Switching to Tenofovir-emtricitabine or Abacavir-lamivudine: The STEAL Study

This study has been completed.
Sponsor:
Information provided by:
Kirby Institute
ClinicalTrials.gov Identifier:
NCT00192634
First received: September 13, 2005
Last updated: May 24, 2011
Last verified: May 2011

September 13, 2005
May 24, 2011
December 2005
August 2008   (final data collection date for primary outcome measure)
virological failure defined by HIV RNA>400copies/mL plasma on 2 consecutive occasions ³4 wks apart(Roche Amplicor v1.5, LLD 50 copies/mL) [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
The primary endpoint is virological failure defined by HIV RNA > 400 copies/mL plasma on two consecutive occasions ³4 weeks apart (Roche Amplicor version 1.5, LLD 50 copies/mL)
Complete list of historical versions of study NCT00192634 on ClinicalTrials.gov Archive Site
  • plasma HIV RNA<50copies/mL; time to virological failure (VF); virological resistance in those with VF; all SAEs; use of concomitant meds for toxicity; adherence; QoL; CD4+lymphocyte count; full blood count; biochemistry; lipid parameters [ Time Frame: Week 48 and 96 ] [ Designated as safety issue: Yes ]
  • glycaemic parameters; DEXA parameters; resolution of AEs; progression to AIDS; death; discontinuation of ART. [ Time Frame: Week 48 and 96 ] [ Designated as safety issue: Yes ]
  • Secondary measures of interest include:
  • 1. plasma HIV RNA <50 copies/mL
  • 2. time to virological failure
  • 3. virological resistance in those with virological failure
  • 4. all serious adverse events, regardless of causality
  • 5. clinical adverse events (all grades and grade 3-4), regardless of causality
  • 6. use of concomitant medications for toxicity
  • 7. adherence (clinician assessed)
  • 8. quality of life (SF-8)
  • 9. CD4+ lymphocyte count
  • 10. full blood count
  • 11. biochemistry
  • 12. lipid parameters
  • 13. glycaemic parameters
  • 14. DEXA parameters
  • 15. non-traumatic bone fractures
  • 16. resolution of adverse events (e.g. dyslipidaemia, low BMD, diabetes)
  • 17. progression to AIDS (Category C)
  • 18. death
  • 19. discontinuation of any ART component
Not Provided
Not Provided
 
A Randomised, Open-label Trial to Assess the Safety and Efficacy of Switching to Tenofovir-emtricitabine or Abacavir-lamivudine: The STEAL Study
A Randomised, Open-label Trial to Assess the Safety and Efficacy of Switching to Tenofovir-emtricitabine or Abacavir-lamivudine: The STEAL Study.

Combination antiretroviral therapy for the treatment of HIV has a high pill burden. Two dual-tablets, abacavir-lamivudine and tenofovir-emtricitabine, are now licensed in the United States and will be available in Australia in December 2005. Data available suggest that the potency of these tablets are similar in controlling replication of the HIV virus, but not have not been directly compared in regard to clinically significant toxicities. We therefore aim to compare the overall safety and efficacy of the two dual-tablets over a 2 year period in HIV infected adults. We hypothesise that the two dual-NRTI treatments will be similar in efficacy and safety.

The aim of this study is to compare the overall safety and efficacy of two dual-NRTI, once daily, tablets over a 2 year period in HIV infected adults.

The study is a randomised, multi-centre, 2 year study of two dual NRTI, once daily tablets in subjects with HIV, currently taking two individual NRTIs as part of their therapy. 350 subjects will be randomised in a 1:1 ratio to either:

  1. tenofovir (TDF) 300mg + emtricitabine (FTC) 200mg OR
  2. abacavir (ABC) 600mg + lamivudine (3TC) 300mg. Subjects will cease their current individual NRTI treatment, commence their randomised dual NRTI tablet, and continue on their current NNRTI or PI therapy.

Subjects will be stratified by the type of NRTI they are currently taking (ABC, TDF or other); whether they are currently taking a protease inhibitor (yes or no); and by the site where they are randomised. A study plan is enclosed

Subjects will be closely monitored (at 1 month and then every 3 months until week 96) for safety by evaluating the incidence and severity of adverse effects/abnormal laboratory parameters. Study investigations enclosed. It is optional whether subjects also provide plasma, serum and cells (PBMCs) for storage. These samples will be available for analysis for sub-studies agreed to through the IVRN expression of interest network.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
HIV Infections
  • Drug: Emtricitabine 200mg - Tenofovir 300mg
    1 tablet once daily for 96 weeks
    Other Name: Truvada
  • Drug: Abacavir 600mg - Lamivudine 300mg
    1 tablet once daily for 96 weeks
    Other Name: Kivexa
  • Active Comparator: 1
    Abacavir 600mg/Lamivudine 300mg
    Intervention: Drug: Abacavir 600mg - Lamivudine 300mg
  • Active Comparator: 2
    Tenofovir 300mg/emtricitabine 200mg
    Intervention: Drug: Emtricitabine 200mg - Tenofovir 300mg

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
357
August 2008
August 2008   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • documented HIV infection
  • age at least 18 years
  • stable (≥ to 12 weeks) ART including at least two NRTIs, currently well tolerated, with no plan to change any other component of the ART regimen at or after baseline
  • HIV RNA < 50 copies/mL plasma for the preceding 12 weeks
  • GFR ≥ 70 mL/min/1.73m2 (estimated by the abbreviated MDRD equation23 estimated GFR = 186 x ([SCR/88.4]-1.154) x age-0.203 x (0.742 if female) x (1.210 if African-American)
  • provision of written, informed consent

Exclusion Criteria:

  • HLA-B*5701 positive at screening OR evidence of previous ABC hypersensitivity OR clinical failure in participants taking abacavir for at least 30 days
  • current therapy comprising triple NRTI therapy alone
  • current use of ABC/3TC FDC (Kivexa) or TDF/FTC FDC (Truvada)
  • history of non-traumatic osteoporotic fracture
  • prior hypersensitivity or intolerance to ABC, 3TC, TDF or FTC
  • prior clinical failure to a regimen containing ABC or TDF
  • prior use of TDF for control of previously active hepatitis B (HBsAg+ or HBV DNA+) in patients likely to be resistant to 3TC/FTC
  • current therapy including unboosted atazanavir
  • concurrent use of aminoglycosides, IV amphotericin B, cidofovir, cisplatin, foscarnet, IV pentamidine, probenecid, adefovir or immunomodulatory agents
  • clinical evidence of cirrhosis (e.g. smooth liver, no features of portal hypertension)
  • creatinine clearance < 50 mL/min (estimated by the Cockcroft-Gault equation)18,19

    • Male: (140 - age in years) x (wt in kg) = CLCr (mL/min) 0.814 x (serum creatinine in µmol/L)
    • Female:(140 - age in years) x (wt in kg) x 0.85 = CLCr (mL/min) 0.814 x (serum creatinine in µmol/L)
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Australia
 
NCT00192634
STEAL, ACTRN012605000505606
Yes
Prof Sean Emery, The National Centre in HIV Epidemiology and Clinical Research
Kirby Institute
Not Provided
Principal Investigator: Andrew Carr, MD FRACP FRCPA Kirby Institute
Kirby Institute
May 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP