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

HIV Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00192634
• Other study ID #: STEAL
• Secondary ID: ACTRN01260500050
• Status: Completed
• Phase: Phase 4
• First received: September 13, 2005
• Last updated: May 24, 2011
• Start date: December 2005
• Est. completion date: August 2008

Study information

• Verified date: May 2011
• Source: Kirby Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 357
• Est. completion date: August 2008
• Est. primary completion date: August 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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)

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Emtricitabine 200mg - Tenofovir 300mg
1 tablet once daily for 96 weeks
• Abacavir 600mg - Lamivudine 300mg
1 tablet once daily for 96 weeks

Locations

Country	Name	City	State
Australia	Flinders Medical Centre	Adelaide	South Australia
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	The Care and Prevention Programme - Adelaide University	Adelaide	South Australia
Australia	Gladstone Road Medical Centre	Brisbane	Queensland
Australia	QLD Health - AIDS Medical Unit	Brisbane	Queensland
Australia	Royal Brisbane and Women's Hospital	Brisbane	Queensland
Australia	Holdsworth House General Practice - Byron Bay	Byron Bay	New South Wales
Australia	Doll's House Clinic - Cairns Base Hospital	Cairns	Queensland
Australia	Fremantle Hospital	Fremantle	Western Australia
Australia	Lismore Sexual Health Clinic - Northen Rivers Area Health Service	Lismore	New South Wales
Australia	Carlton Clinic	Melbourne	Victoria
Australia	Melbourne Sexual Health Centre	Melbourne	Victoria
Australia	Monash Medical Centre	Melbourne	Victoria
Australia	Prahran Market Clinic	Melbourne	Victoria
Australia	Royal Melbourne Hospital	Melbourne	Victoria
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	The Centre Clinic	Melbourne	Victoria
Australia	Gold Coast Sexual Health Clinic	Miami	Queensland
Australia	Clinic 87, Nambour Hospital	Nambour	Queensland
Australia	John Hunter Hospital	Newcastle	New South Wales
Australia	Royal Perth Hospital	Perth	Western Australia
Australia	407 Doctors	Sydney	New South Wales
Australia	Albion Street Centre	Sydney	New South Wales
Australia	Burwood Road Practice	Sydney	New South Wales
Australia	Clinic 16, Royal North Shore Hospital	Sydney	New South Wales
Australia	Holdsworth House General Practice	Sydney	New South Wales
Australia	Liverpool Health Service	Sydney	New South Wales
Australia	Prince of Wales Hospital	Sydney	New South Wales
Australia	St. Vincent's Hospital	Sydney	New South Wales
Australia	Taylor Square Private Clinic	Sydney	New South Wales
Australia	Westmead Hospital	Sydney	New South Wales

Sponsors (1)

Lead Sponsor	Collaborator
Kirby Institute

Country where clinical trial is conducted

Australia, 

References & Publications (1)

Martin A, Bloch M, Amin J, Baker D, Cooper DA, Emery S, Carr A. Simplification of antiretroviral therapy with tenofovir-emtricitabine or abacavir-Lamivudine: a randomized, 96-week trial. Clin Infect Dis. 2009 Nov 15;49(10):1591-601. doi: 10.1086/644769. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	Yes
Secondary	glycaemic parameters; DEXA parameters; resolution of AEs; progression to AIDS; death; discontinuation of ART.		Week 48 and 96	Yes

External Links

•   National Centre in HIV Epidemiology and Clinical Research Homepage