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

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:

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Lamivudine Abacavir Emtricitabine Tenofovir Abacavir sulfate Tenofovir Disoproxil Fumarate

U.S. FDA Resources

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:

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 (Adult, Senior)
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
407 Doctors
Sydney, New South Wales, Australia, 2010
Albion Street Centre
Sydney, New South Wales, Australia, 2010
Holdsworth House General Practice
Sydney, New South Wales, Australia, 2010
St. Vincent's Hospital
Sydney, New South Wales, Australia, 2010
Taylor Square Private Clinic
Sydney, New South Wales, Australia, 2010
Prince of Wales Hospital
Sydney, New South Wales, Australia, 2031
Clinic 16, Royal North Shore Hospital
Sydney, New South Wales, Australia, 2065
Burwood Road Practice
Sydney, New South Wales, Australia, 2134
Westmead Hospital
Sydney, New South Wales, Australia, 2145
Liverpool Health Service
Sydney, New South Wales, Australia, 2170
Australia, Queensland
QLD Health - AIDS Medical Unit
Brisbane, Queensland, Australia, 4002
Royal Brisbane and Women's Hospital
Brisbane, Queensland, Australia, 4029
Gladstone Road Medical Centre
Brisbane, Queensland, Australia, 4101
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
Royal Adelaide Hospital
Adelaide, South Australia, Australia, 5000
The Care and Prevention Programme - Adelaide University
Adelaide, South Australia, Australia, 5000
Flinders Medical Centre
Adelaide, South Australia, Australia, 5042
Australia, Victoria
The Alfred Hospital
Melbourne, Victoria, Australia, 3004
Carlton Clinic
Melbourne, Victoria, Australia, 3053
Melbourne Sexual Health Centre
Melbourne, Victoria, Australia, 3053
Prahran Market Clinic
Melbourne, Victoria, Australia, 3141
Monash Medical Centre
Melbourne, Victoria, Australia, 3168
The Centre Clinic
Melbourne, Victoria, Australia, 3182
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:

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

Publications:

http://www.retroconference.org/AbstractSearch/Default.aspx?Conf=18

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Haskelberg H, Pocock N, Amin J, Ebeling PR, Emery S, Carr A; STEAL study investigators, Allworth A. Hip structural parameters over 96 weeks in HIV-infected adults switching treatment to tenofovir-emtricitabine or abacavir-lamivudine. PLoS One. 2014 Apr 10;9(4):e94858. doi: 10.1371/journal.pone.0094858. eCollection 2014.

Haskelberg H, Cordery DV, Amin J, Kelleher AD, Cooper DA, Emery S; STEAL Study Group. HLA alleles association with changes in bone mineral density in HIV-1-infected adults changing treatment to tenofovir-emtricitabine or abacavir-lamivudine. PLoS One. 2014 Mar 28;9(3):e93333. doi: 10.1371/journal.pone.0093333. eCollection 2014.


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:


HIV Infections Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Tenofovir Emtricitabine Lamivudine	Abacavir Dideoxynucleosides Antiviral Agents Anti-Infective Agents Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-Retroviral Agents Anti-HIV Agents Antimetabolites

ClinicalTrials.gov processed this record on September 23, 2016