A Randomised, Open-Label Trial to Assess the Safety and Efficacy of Switching to Tenofovir-Emtricitabine or Abacavir-Lamivudine: The STEAL Study - Full Text View

Sponsored by:	The National Centre in HIV Epidemiology and Clinical Research
Information provided by:	The National Centre in HIV Epidemiology and Clinical Research
ClinicalTrials.gov Identifier:	NCT00192634

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 IV

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
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:

MedlinePlus related topics: AIDS

Drug Information available for: Lamivudine Abacavir Tenofovir Abacavir sulfate Tenofovir disoproxil Tenofovir Disoproxil Fumarate Abacavir-lamivudine combination

U.S. FDA Resources

Further study details as provided by The National Centre in HIV Epidemiology and Clinical Research:

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)

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
glycaemic parameters; DEXA parameters; resolution of AEs; progression to AIDS; death; discontinuation of ART.

Estimated Enrollment:	350
Study Start Date:	December 2005
Estimated Study Completion Date:	July 2008

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:

tenofovir (TDF) 300mg + emtricitabine (FTC) 200mg OR
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

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

Contacts

Contact: Allison Humphries, MSc GradDipPH	+61 2 9385 0900	ahumphries@nchecr.unsw.edu.au
Contact: Sean Emery, PhD	+61 2 9385 0900	semery@nchecr.unsw.edu.au

Locations

Australia, New South Wales
Lismore Sexual Health Clinic - Northen Rivers Area Health Service	Recruiting
Lismore, New South Wales, Australia, 2480
Contact: Denni Pearson +61 (02) 6620-2980 dennip@nrahs.nsw.gov.au
Principal Investigator: David Smith
John Hunter Hospital	Recruiting
Newcastle, New South Wales, Australia, 2304
Contact: Leah Carrall +61 2 4921 4766 Leah.Carrall@hnehealth.nsw.gov.au
Contact: Pauline Dobson +61 2 4921 4766 Pauline.Dobson@hnehealth.nsw.gov.au
Principal Investigator: Michael Boyle
Clinic 16, Royal North Shore Hospital	Recruiting
Sydney, New South Wales, Australia, 2065
Contact: James Baber +61 (02) 9926-7414 JBaber@nsccahs.health.nsw.gov.au
Principal Investigator: Linda Dayan
St. Vincent's Hospital	Recruiting
Sydney, New South Wales, Australia, 2010
Contact: Richard Norris +61 (02) 8382-2435 rnorris@stvincents.com.au
Principal Investigator: Andrew Carr, MD FRACP FRCPA
Burwood Road Practice	Recruiting
Sydney, New South Wales, Australia, 2134
Contact: Jeff Hudson +61 (02) 9745-2755 burwood8@bigpond.net.au
Principal Investigator: Nicholas Doong
Holdsworth House General Practice	Recruiting
Sydney, New South Wales, Australia, 2010
Contact: Shikha Agrawal +61 (02) 9331-7822 trials@holdsworthhouse.com.au
Principal Investigator: Mark Bloch
Holdsworth House General Practice - Byron Bay	Recruiting
Byron Bay, New South Wales, Australia, 2481
Contact: Debra Hayhoe +61 (02) 6680-7211 dhayhoe@holdsworthhouse.com.au
Principal Investigator: Janet Knox
Westmead Hospital	Recruiting
Sydney, New South Wales, Australia, 2145
Contact: Margaret Piper +61 (02) 9845-6251 margaretp@icpmr.wsahs.nsw.gov.au
Principal Investigator: Dominic Dwyer
Taylor Square Private Clinic	Recruiting
Sydney, New South Wales, Australia, 2010
Contact: Sophie Dinning +61 (02) 9331-6151 sdinning@tspc.com.au
Contact: Robyn Richardson +61 (02) 9331-6151 robynr@tspc.com.au
Principal Investigator: Robert Finlayson
Prince of Wales Hospital	Recruiting
Sydney, New South Wales, Australia, 2031
Contact: Suzanne Ryan +61 (02) 9382-3408 ryans@sesahs.nsw.gov.au
Principal Investigator: Jeffrey Post
Albion Street Centre	Recruiting
Sydney, New South Wales, Australia, 2010
Contact: Jason Gao +61 (02) 9332-9705 Jason.Gao@sesiahs.health.nsw.gov.au
Principal Investigator: Don Smith
407 Doctors	Recruiting
Sydney, New South Wales, Australia, 2010
Contact: Robyn Vale +61 (02) 9332-2531 robynv@407.com.au
Principal Investigator: David Baker
Liverpool Health Service	Recruiting
Sydney, New South Wales, Australia, 2170
Contact: Helen Best +61 (02) 9827-8038 Helen.Best@swsahs.nsw.gov.au
Principal Investigator: John Quin, MD
Australia, Queensland
Clinic 87, Nambour Hospital	Recruiting
Nambour, Queensland, Australia, 4560
Contact: Colleen Shields +61 (07) 5476-2489 Colleen_shields@health.qld.gov.au
Principal Investigator: David Sowden, MB BS RACOG FRACP FRCPA
Doll's House Clinic - Cairns Base Hospital	Recruiting
Cairns, Queensland, Australia, 4870
Contact: Joanne Leamy +61 (07) 4050-6205 Joanne_Leamy@health.qld.gov.au
Principal Investigator: Darren Russell
Gold Coast Sexual Health Clinic	Recruiting
Miami, Queensland, Australia, 4220
Contact: Denise Lester +61 (07) 5576 9033 DeniseJ_Lester@health.qld.gov.au
Contact: Tammy Schmidt + 61 (07) 5576 9033 tammy_schmidt@health.qld.gov.au
Principal Investigator: John Chuah
QLD Health - AIDS Medical Unit	Recruiting
Brisbane, Queensland, Australia, 4002
Contact: Paul Negus +61 (07) 3837-5622 paul_negus@health.qld.gov.au.
Principal Investigator: Mark Kelly
Royal Brisbane and Women's Hospital	Recruiting
Brisbane, Queensland, Australia, 4029
Contact: Janelle Zillmann +61 (07) 3636-7324 Janelle_Zillmann@health.qld.gov.au
Principal Investigator: Anthony Allworth
Gladstone Road Medical Centre	Recruiting
Brisbane, Queensland, Australia, 4101
Contact: David Youds +61 (07) 3844-9599 d.youds123@optusnet.com.au
Principal Investigator: David Orth
Australia, South Australia
Royal Adelaide Hospital	Recruiting
Adelaide, South Australia, Australia, 5000
Contact: Lyndal Daly +61 (08) 8222-5635 ldaly@mail.rah.sa.gov.au
Principal Investigator: David Shaw
Flinders Medical Centre	Recruiting
Adelaide, South Australia, Australia, 5042
Contact: Robyn Gilligan +61 8 8204-4292 robyn.gilligan@fmc.sa.gov.au
Principal Investigator: Mark Boyd
The Care and Prevention Programme - Adelaide University	Recruiting
Adelaide, South Australia, Australia, 5000
Contact: Michael Curry +61 8 8231-4026 Michael@careandprevention.org
Principal Investigator: Gary Rogers, MD
Australia, Victoria
Melbourne Sexual Health Centre	Recruiting
Melbourne, Victoria, Australia, 3053
Contact: Helen Kent +61 (03) 9347-4144 researchunit@mshc.org.au
Contact: Julie Silvers +61 (03) 9347-4144 jsilvers@mshc.org.au
Principal Investigator: Tim Read
Carlton Clinic	Recruiting
Melbourne, Victoria, Australia, 3053
Contact: Kaye Lowe +61 (03) 9347-9422 kaye.lowe@maynemc.com
Principal Investigator: Jonathan Anderson
The Alfred Hospital	Recruiting
Melbourne, Victoria, Australia, 3004
Contact: Christine Alverez +61 (03) 9276-6908 clinresearch@alfred.org.au
Principal Investigator: Jenny Hoy
Royal Melbourne Hospital	Recruiting
Melbourne, Victoria, Australia, 3403
Contact: Janine Roney +61 (03) 9342-7212 janine.roney@mh.org.au
Principal Investigator: Alan Street
Prahran Market Clinic	Recruiting
Melbourne, Victoria, Australia, 3141
Contact: Helen Wood +61 (03) 9826-4500 hpwood@optusnet.com.au
Principal Investigator: Norman Roth
The Centre Clinic	Recruiting
Melbourne, Victoria, Australia, 3182
Contact: Helen Wood +61 (3 9525) 5866 hpwood@optusnet.com.au
Principal Investigator: Nicholas Medland
Monash Medical Centre	Recruiting
Melbourne, Victoria, Australia, 3168
Contact: Pauline Galt +61 (03) 9594-3048 pauline.galt@southernhealth.org.au
Principal Investigator: Ian Woolley
Australia, Western Australia
Royal Perth Hospital	Recruiting
Perth, Western Australia, Australia, 6000
Contact: Claire Forsdyke +61 (08) 9224-3427 claire.forsdyke@health.wa.gov.au
Principal Investigator: David Nolan
Fremantle Hospital	Recruiting
Fremantle, Western Australia, Australia, 6160
Contact: Jacqueline Kerth +61 (08) 9431-2182 jacqueline.kerth@health.wa.gov.au
Principal Investigator: John Dyer

Sponsors and Collaborators

The National Centre in HIV Epidemiology and Clinical Research

Investigators

Principal Investigator:

Andrew Carr, MD FRACP FRCPA

The National Centre in HIV Epidemiology and Clinical Research

More Information

Additional Information:

National Centre in HIV Epidemiology and Clinical Research Homepage This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	STEAL, ACTRN012605000505606
Study First Received:	September 13, 2005
Last Updated:	June 13, 2006
ClinicalTrials.gov Identifier:	NCT00192634 History of Changes
Health Authority:	Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by The National Centre in HIV Epidemiology and Clinical Research:

HIV
Antiretroviral therapy
nucleoside analogue reverse transcriptase
fixed dose combination
Treatment Experienced

Study placed in the following topic categories:

Anti-Infective Agents
Sexually Transmitted Diseases, Viral
Anti-HIV Agents
Acquired Immunodeficiency Syndrome
Lamivudine
Antiviral Agents
Immunologic Deficiency Syndromes
Reverse Transcriptase Inhibitors
Virus Diseases

Anti-Retroviral Agents
Emtricitabine
HIV Infections
Sexually Transmitted Diseases
Tenofovir
Abacavir
Retroviridae Infections
Tenofovir disoproxil

Additional relevant MeSH terms:

Anti-Infective Agents
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Lamivudine
Infection
Reverse Transcriptase Inhibitors
Emtricitabine
Anti-Retroviral Agents
Therapeutic Uses
Tenofovir
Abacavir
Retroviridae Infections
Nucleic Acid Synthesis Inhibitors

Tenofovir disoproxil
RNA Virus Infections
Anti-HIV Agents
Immune System Diseases
Acquired Immunodeficiency Syndrome
Enzyme Inhibitors
Antiviral Agents
Immunologic Deficiency Syndromes
Pharmacologic Actions
Virus Diseases
HIV Infections
Sexually Transmitted Diseases
Lentivirus Infections

ClinicalTrials.gov processed this record on September 02, 2009