Safety and Efficacy of Reduced Dose Efavirenz (EFV) With Standard Dose EFV Plus Two Nucleotide Reverse Transcriptase Inhibitors (N(t)RTI) in Antiretroviral-naïve HIV-infected Individuals. (encore1)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Kirby Institute
ClinicalTrials.gov Identifier:
NCT01011413
First received: November 9, 2009
Last updated: November 6, 2012
Last verified: November 2012
  Purpose

Clinical data suggests that the standard dose of the anti-HIV medication, efavirenz (EFV), could be reduced without compromising its effectiveness. Lower drug doses could have fewer side effects and would make EFV more affordable. The purpose of this study is to compare the safety and effectiveness, over 96 weeks, of standard (600mg) versus reduced dose (400mg) EFV in controlling HIV as part of initial combination antiretroviral therapy.


Condition Intervention Phase
HIV Infections
Drug: Efavirenz
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomised, Double-blind, Placebo-controlled, Clinical Trial to Compare the Safety and Efficacy of Reduced Dose Efavirenz (EFV) With Standard Dose EFV Plus Two Nucleotide Reverse Transcriptase Inhibitors (N(t)RTI) in Antiretroviral-naïve HIV-infected Individuals Over 96 Weeks

Resource links provided by NLM:


Further study details as provided by Kirby Institute:

Primary Outcome Measures:
  • The primary endpoint is the comparison between treatment groups of proportions of patients with HIV RNA <200 copies/mL 48 weeks after randomisation [ Time Frame: 1.5 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Virologic endpoints: proportion of patients with plasma HIV RNA <400 copies/mL and <50 copies/mL, and time to virological failure (HIV RNA ≥200 copies/ml) [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Immunologic endpoints: mean change from baseline in CD4+ T cell count/µL [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Clinical endpoints: rate of opportunistic disease or death, and rates of serious non-AIDS-defining illness and non-AIDS-related mortality [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Metabolic endpoints: mean/median change from baseline in fasted lipids (TC, LDL-c, HDL-c and TG), mean/median change from baseline in fasted glucose, and rates of initiation or changes in existing lipid-lowering therapies [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Adherence: median scores of self-reported adherence to randomised study medications [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Mean/median change from baseline in selected serum biochemical parameters [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Rates, types and severity of adverse events [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Steady state EFV concentrations [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Steady state EFV concentrations measured by plasma and dried blood spot samples


Estimated Enrollment: 630
Study Start Date: September 2011
Estimated Study Completion Date: May 2014
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 600mg Efavirenz
Eligible patients will be centrally randomised to receive tenofovir (TDF) (300mg qd)/emtricitabine (FTC) (200mg qd) + EFV (600mg qd; 3 x 200mg qd)
Drug: Efavirenz
3 x EFV 200mg tablets once daily
Other Name: Matrix EFV 200mg (Efamat 200) tablets
Experimental: 400mg Efavirenz
Eligible patients will be centrally randomised to receive TDF (300mg qd)/FTC (200mg qd) + EFV (400mg qd; 2 x 200mg + 1 x 200mg placebo qd).
Drug: Efavirenz
2 x EFV 200mg tablets plus 1x matched EFV placebo tablet once daily
Other Names:
  • Matrix EFV 200mg (Efamat 200) tablets
  • Matrix EFV 200mg (Efamat 200) matched placebo tablets.

Detailed Description:

In this international, multicenter trial, 630 HIV infected patients who have not received any previous treatment for their HIV-infection will be enrolled. Participants will be randomized equally (1:1) to receive truvada (tenofovir and emtricitabine) with either the standard or reduced dose of EFV. Neither the study doctor nor the participant will know which treatment the participant is receiving. Physical examinations, laboratory analyses and questionnaires will be performed at the 11 study visits at screening, baseline (Week 0), Weeks 4, 12, 24, 36, 48, 60, 72, 84 and 96. The primary aim of this study is to compare between treatment groups the proportion of patients with undetectable HIV viral load (HIV RNA < 200 copies/mL) after 48 weeks. Information on immune function, drug adherence, resistance to antiretrovirals, quality of life, mental state and HIV-related conditions will also be collected. Blood samples will be collected for future testing. Interim analyses will be performed when the first 125 participants in each treatment group reach week 24 and when all participants reach week 24. These interim analyses will provide an early check that the reduced dose of EFV suppresses HIV infection as effectively as the standard dose of EFV. A follow-up analysis will be performed when all participants reach week 96.

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV-1 positive by licensed diagnostic test
  • aged >16 years of age (or minimum age as determined by local regulations or as legal requirements dictate)
  • 50 < CD4 <500 cells/µL
  • No prior AIDS-defining illness, using the CDC 1993 case definition (except pulmonary tuberculosis)
  • HIV RNA ≥1000 copies/mL
  • no prior exposure to ART (including short course ARVs for preventing MTCT)
  • calculated creatinine clearance (CLCr) more than or equal to 50 mL/min (Cockcroft-Gault formula)
  • provision of written informed consent.

Exclusion Criteria:

  • the following laboratory values:

    • absolute neutrophil count (ANC) <500 cells/μL
    • hemoglobin <7.0 g/dL
    • platelet count <50,000 cells/μL
    • AST and/or ALT >5 x ULN
  • pregnant women or nursing mothers
  • active opportunistic or malignant disease not under adequate control
  • use of immunomodulators within 30 days prior to screening
  • use of any prohibited medications
  • current alcohol or illicit substance use that might adversely affect study participation
  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: NCT01011413

Locations
Australia, New South Wales
St Vincent's Hospital
Sydney, New South Wales, Australia, 2010
Sponsors and Collaborators
Kirby Institute
Investigators
Principal Investigator: David Cooper, Professor Kirby Institute
  More Information

Additional Information:
No publications provided by Kirby Institute

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Kirby Institute
ClinicalTrials.gov Identifier: NCT01011413     History of Changes
Other Study ID Numbers: NCHECR-ENCORE1
Study First Received: November 9, 2009
Last Updated: November 6, 2012
Health Authority: Australia: Human Research Ethics Committee
Australia: Department of Health and Ageing Therapeutic Goods Administration
United Kingdom: National Institute for Health Research
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Kirby Institute:
HIV
ART
Efavirenz
Dose reduction

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Reverse Transcriptase Inhibitors
Efavirenz
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 18, 2014