Clinical trial NCT00192634: A Randomised, Open-label Trial to Assess the Safety and Efficacy of Switching to Tenofovir-emtricitabine or Abacavir-lamivudine: The STEAL 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV Infections
Keywords: HIV
Antiretroviral therapy
nucleoside analogue reverse transcriptase
fixed dose combination
Treatment Experienced
Lead sponsor: Kirby Institute
Sponsor class: OTHER_GOV
First posted: 2005-09-19
Enrollment: 357
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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)

Primary outcomes:
measure: virological failure defined by HIV RNA>400copies/mL plasma on 2 consecutive occasions ³4 wks apart(Roche Amplicor v1.5, LLD 50 copies/mL)
timeFrame: Week 48
Secondary outcomes:
measure: 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
timeFrame: Week 48 and 96
measure: glycaemic parameters; DEXA parameters; resolution of AEs; progression to AIDS; death; discontinuation of ART.
timeFrame: Week 48 and 96
Other outcomes:
Locations:
city: Byron Bay
country: Australia
facility: Holdsworth House General Practice - Byron Bay
state: New South Wales
city: Lismore
country: Australia
facility: Lismore Sexual Health Clinic - Northen Rivers Area Health Service
state: New South Wales
city: Newcastle
country: Australia
facility: John Hunter Hospital
state: New South Wales
city: Sydney
country: Australia
facility: 407 Doctors
state: New South Wales
city: Sydney
country: Australia
facility: Albion Street Centre
state: New South Wales
city: Sydney
country: Australia
facility: Holdsworth House General Practice
state: New South Wales
city: Sydney
country: Australia
facility: St. Vincent's Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Taylor Square Private Clinic
state: New South Wales
city: Sydney
country: Australia
facility: Prince of Wales Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Clinic 16, Royal North Shore Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Burwood Road Practice
state: New South Wales
city: Sydney
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Liverpool Health Service
state: New South Wales
city: Brisbane
country: Australia
facility: QLD Health - AIDS Medical Unit
state: Queensland
city: Brisbane
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queensland
city: Brisbane
country: Australia
facility: Gladstone Road Medical Centre
state: Queensland
city: Cairns
country: Australia
facility: Doll's House Clinic - Cairns Base Hospital
state: Queensland
city: Miami
country: Australia
facility: Gold Coast Sexual Health Clinic
state: Queensland
city: Nambour
country: Australia
facility: Clinic 87, Nambour Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Adelaide
country: Australia
facility: The Care and Prevention Programme - Adelaide University
state: South Australia
city: Adelaide
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Carlton Clinic
state: Victoria
city: Melbourne
country: Australia
facility: Melbourne Sexual Health Centre
state: Victoria
city: Melbourne
country: Australia
facility: Prahran Market Clinic
state: Victoria
city: Melbourne
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Melbourne
country: Australia
facility: The Centre Clinic
state: Victoria
city: Melbourne
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Fremantle
country: Australia
facility: Fremantle Hospital
state: Western Australia
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
Study officials:
affiliation: Kirby Institute
name: Andrew Carr, MD FRACP FRCPA
role: PRINCIPAL_INVESTIGATOR
References:
citation: http://www.retroconference.org/AbstractSearch/Default.aspx?Conf=18
citation: 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.
citation: 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.
citation: 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.