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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
  Purpose

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.


Condition Intervention Phase
HIV Infections
Drug: Emtricitabine 200mg - Tenofovir 300mg
Drug: Abacavir 600mg - Lamivudine 300mg
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomised, Open-label Trial to Assess the Safety and Efficacy of Switching to Tenofovir-emtricitabine or Abacavir-lamivudine: The STEAL Study.

Resource links provided by NLM:


Further study details as provided by Kirby Institute:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 357
Study Start Date: December 2005
Study Completion Date: August 2008
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Abacavir 600mg/Lamivudine 300mg
Drug: Abacavir 600mg - Lamivudine 300mg
1 tablet once daily for 96 weeks
Other Name: Kivexa
Active Comparator: 2
Tenofovir 300mg/emtricitabine 200mg
Drug: Emtricitabine 200mg - Tenofovir 300mg
1 tablet once daily for 96 weeks
Other Name: Truvada

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00192634

Locations
Australia, New South Wales
Holdsworth House General Practice - Byron Bay
Byron Bay, New South Wales, Australia, 2481
Lismore Sexual Health Clinic - Northen Rivers Area Health Service
Lismore, New South Wales, Australia, 2480
John Hunter Hospital
Newcastle, New South Wales, Australia, 2304
Westmead Hospital
Sydney, New South Wales, Australia, 2145
Albion Street Centre
Sydney, New South Wales, Australia, 2010
Burwood Road Practice
Sydney, New South Wales, Australia, 2134
Clinic 16, Royal North Shore Hospital
Sydney, New South Wales, Australia, 2065
Holdsworth House General Practice
Sydney, New South Wales, Australia, 2010
Liverpool Health Service
Sydney, New South Wales, Australia, 2170
Prince of Wales Hospital
Sydney, New South Wales, Australia, 2031
St. Vincent's Hospital
Sydney, New South Wales, Australia, 2010
Taylor Square Private Clinic
Sydney, New South Wales, Australia, 2010
407 Doctors
Sydney, New South Wales, Australia, 2010
Australia, Queensland
Gladstone Road Medical Centre
Brisbane, Queensland, Australia, 4101
QLD Health - AIDS Medical Unit
Brisbane, Queensland, Australia, 4002
Royal Brisbane and Women's Hospital
Brisbane, Queensland, Australia, 4029
Doll's House Clinic - Cairns Base Hospital
Cairns, Queensland, Australia, 4870
Gold Coast Sexual Health Clinic
Miami, Queensland, Australia, 4220
Clinic 87, Nambour Hospital
Nambour, Queensland, Australia, 4560
Australia, South Australia
The Care and Prevention Programme - Adelaide University
Adelaide, South Australia, Australia, 5000
Royal Adelaide Hospital
Adelaide, South Australia, Australia, 5000
Flinders Medical Centre
Adelaide, South Australia, Australia, 5042
Australia, Victoria
The Centre Clinic
Melbourne, Victoria, Australia, 3182
Carlton Clinic
Melbourne, Victoria, Australia, 3053
Melbourne Sexual Health Centre
Melbourne, Victoria, Australia, 3053
Monash Medical Centre
Melbourne, Victoria, Australia, 3168
Prahran Market Clinic
Melbourne, Victoria, Australia, 3141
The Alfred Hospital
Melbourne, Victoria, Australia, 3004
Royal Melbourne Hospital
Melbourne, Victoria, Australia, 3403
Australia, Western Australia
Fremantle Hospital
Fremantle, Western Australia, Australia, 6160
Royal Perth Hospital
Perth, Western Australia, Australia, 6000
Sponsors and Collaborators
Kirby Institute
Investigators
Principal Investigator: Andrew Carr, MD FRACP FRCPA Kirby Institute
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Prof Sean Emery, The National Centre in HIV Epidemiology and Clinical Research
ClinicalTrials.gov Identifier: NCT00192634     History of Changes
Other Study ID Numbers: STEAL, ACTRN012605000505606
Study First Received: September 13, 2005
Last Updated: May 24, 2011
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Kirby Institute:
HIV
Antiretroviral therapy
nucleoside analogue reverse transcriptase
fixed dose combination
Treatment Experienced

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Abacavir
Emtricitabine
Lamivudine
Tenofovir
Tenofovir disoproxil
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014