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. - Full Text View

Sponsor:	The National Centre in HIV Epidemiology and Clinical Research
Information provided by:	The National Centre in HIV Epidemiology and Clinical Research
ClinicalTrials.gov Identifier:	NCT01011413

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. 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 96 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.

Condition	Intervention	Phase
HIV Infections	Drug: Efavirenz	Phase I

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Investigator), Dose Comparison, Parallel Assignment, Safety/Efficacy Study
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:

MedlinePlus related topics: AIDS

Drug Information available for: Efavirenz

U.S. FDA Resources

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

Primary Outcome Measures:

The primary endpoint is the comparison between treatment groups of proportions of patients with HIV RNA <200 copies/mL 96 weeks after randomisation [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Virologic endpoints: proportion of patients at 96 weeks 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 to week 96 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 to week 96 in fasted lipids (TC, LDL-c, HDL-c and TG), mean/median change from baseline to week 96 changes 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 ]

Estimated Enrollment:	630
Study Start Date:	April 2010
Estimated Study Completion Date:	June 2012
Estimated Primary Completion Date:	April 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Normal Efavirenz dose arm: Active Comparator 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 600mg qd; 3 x 200mg qd
Reduced dose Efavirenz arm: Experimental 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 400mg qd; 2 x 200mg

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 <350 cells/µL or previous AIDS-defining illness
HIV RNA ≥1000 copies/mL
no prior exposure to ART (including short course ARVs for preventing MTCT)
derived creatinine clearance (CLCr) > and = 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

Please refer to this study by its ClinicalTrials.gov identifier: NCT01011413

Contacts

Contact: Rebekah Puls, PhD

+61293850900

Sponsors and Collaborators

The National Centre in HIV Epidemiology and Clinical Research

Investigators

Principal Investigator:

David Cooper, Professor

The National Centre in HIV Epidemiology and Clinical Research

More Information

Additional Information:

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

No publications provided

Responsible Party:	Therapeutic and Vaccine Research Program, NCHECR ( Dr Rebekah Puls )
Study ID Numbers:	NCHECR-ENCORE1
Study First Received:	November 9, 2009
Last Updated:	November 10, 2009
ClinicalTrials.gov Identifier:	NCT01011413 History of Changes
Health Authority:	Australia: Human Research Ethics Committee; United Kingdom: National Institute for Health Research

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

HIV
ART
Efavirenz
Dose reduction

Additional relevant MeSH terms:

Anti-Infective Agents
Efavirenz
RNA Virus Infections
Sexually Transmitted Diseases, Viral
Anti-HIV Agents
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Acquired Immunodeficiency Syndrome
Enzyme Inhibitors
Infection
Antiviral Agents

Pharmacologic Actions
Immunologic Deficiency Syndromes
Reverse Transcriptase Inhibitors
Virus Diseases
Anti-Retroviral Agents
HIV Infections
Therapeutic Uses
Sexually Transmitted Diseases
Lentivirus Infections
Retroviridae Infections
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on February 08, 2010