A Randomised, Open-label Trial to Assess the Safety and Efficacy of Switching to Tenofovir-emtricitabine or Abacavir-lamivudine: The STEAL Study
- Conditions
- HIV Infections
- Interventions
- Registration Number
- NCT00192634
- Lead Sponsor
- Kirby Institute
- Brief Summary
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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 357
- 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
-
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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 1 Abacavir 600mg - Lamivudine 300mg Abacavir 600mg/Lamivudine 300mg 2 Emtricitabine 200mg - Tenofovir 300mg Tenofovir 300mg/emtricitabine 200mg
- Primary Outcome Measures
Name Time Method virological failure defined by HIV RNA>400copies/mL plasma on 2 consecutive occasions ³4 wks apart(Roche Amplicor v1.5, LLD 50 copies/mL) Week 48
- Secondary Outcome Measures
Name Time Method 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 Week 48 and 96 glycaemic parameters; DEXA parameters; resolution of AEs; progression to AIDS; death; discontinuation of ART. Week 48 and 96
Trial Locations
- Locations (31)
QLD Health - AIDS Medical Unit
🇦🇺Brisbane, Queensland, Australia
John Hunter Hospital
🇦🇺Newcastle, New South Wales, Australia
The Centre Clinic
🇦🇺Melbourne, Victoria, Australia
Holdsworth House General Practice - Byron Bay
🇦🇺Byron Bay, New South Wales, Australia
Lismore Sexual Health Clinic - Northen Rivers Area Health Service
🇦🇺Lismore, New South Wales, Australia
Doll's House Clinic - Cairns Base Hospital
🇦🇺Cairns, Queensland, Australia
Gold Coast Sexual Health Clinic
🇦🇺Miami, Queensland, Australia
The Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
Royal Brisbane and Women's Hospital
🇦🇺Brisbane, Queensland, Australia
Clinic 87, Nambour Hospital
🇦🇺Nambour, Queensland, Australia
Gladstone Road Medical Centre
🇦🇺Brisbane, Queensland, Australia
Royal Melbourne Hospital
🇦🇺Melbourne, Victoria, Australia
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
The Care and Prevention Programme - Adelaide University
🇦🇺Adelaide, South Australia, Australia
407 Doctors
🇦🇺Sydney, New South Wales, Australia
Albion Street Centre
🇦🇺Sydney, New South Wales, Australia
Holdsworth House General Practice
🇦🇺Sydney, New South Wales, Australia
Taylor Square Private Clinic
🇦🇺Sydney, New South Wales, Australia
Prince of Wales Hospital
🇦🇺Sydney, New South Wales, Australia
Clinic 16, Royal North Shore Hospital
🇦🇺Sydney, New South Wales, Australia
Burwood Road Practice
🇦🇺Sydney, New South Wales, Australia
Liverpool Health Service
🇦🇺Sydney, New South Wales, Australia
Flinders Medical Centre
🇦🇺Adelaide, South Australia, Australia
Royal Perth Hospital
🇦🇺Perth, Western Australia, Australia
Fremantle Hospital
🇦🇺Fremantle, Western Australia, Australia
St. Vincent's Hospital
🇦🇺Sydney, New South Wales, Australia
Westmead Hospital
🇦🇺Sydney, New South Wales, Australia
Melbourne Sexual Health Centre
🇦🇺Melbourne, Victoria, Australia
Monash Medical Centre
🇦🇺Melbourne, Victoria, Australia
Prahran Market Clinic
🇦🇺Melbourne, Victoria, Australia
Carlton Clinic
🇦🇺Melbourne, Victoria, Australia