FREE Study: Efficacy and Toxicity of Trizivir

Free Study: a Randomised, Open Label, Multicentre Strategic Study to Evaluate the Efficacy and Toxicity of an Early Switch From a PI-containing Regimen to Trizivir ® on Guidance of Viral Load in HIV-1 Infected , Antiretroviral naïve Adults

Antiretroviral naïve patients with <350 xE6/l CD4 cells and a HIV-viral load of > 30.000 cop/ml are started on combivir ® and Kaletra ®. When patients have reached an undetectable viral load of< 50 cop/ml on two consecutive occasions at least at week 12, but no later than week 24, they are randomised in either continuation with Combivir/Kaletra or switch to Trizivir ® twice daily one pill during 96 weeks. All patients randomised in the combivir/Kaletra arm are eligible to switch to Trizivir at any post randomisation visit when they reach predefined switch criteria for elevated levels of fasting glucose or lipids.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: zidovudine,lamivudine,abacavir; Drug: Trizivir

Detailed Description

The primary objective is to compare the antiviral efficacy of an early switch from a boosted PI/2NRTI regimen to Trizivir (after undetectability of HIV-RNA has been achieved on 2 consecutive occasions) with uninterrupted use of the PI/2NRTI regimen for 96 weeks.

• Study Type: Interventional
• Enrollment (Actual): 207
• Phase: Phase 3

Contacts and Locations

Study Locations

• Netherlands
  • Gelderland
    • Arnhem, Gelderland, Netherlands, 6800 TA
      • Rijnstate Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults >18 years of age, confirmed HIV-1 infection, never received antiretrovirals before, plasma-HIV-RNA >30.000 cop/ml, CD4 < 350 E6/l.

Exclusion Criteria:

• pregnancy, women using proven barrier methods of contraception, defined uncontrolled active AIDS defining complication, being on treatment for diabetes, other serious illnesses, expected non-compliance, defined laboratory abnormalities

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: combivir/kaletra; All patients started with combivir/Kaletra and were randomized if they reached undetectable viral load (2 times) within 24 weeks into continuation of the same regimen or Trizivir (2 arms)	Drug: zidovudine,lamivudine,abacavir; zidovudine 300 mg bid, lamivudine 150mg bid, abacavir 300mg bid
Experimental: Trizivir; patients who reach undetectable HIV-RNA within 24 weeks are randomized to switch to trizivir or continuation of combivir/kaletra	Drug: Trizivir

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Plasma HIV-RNA < 400 cop/ml at week 96 for the Intent- To-Treat (ITT).

Secondary Outcome Measures

Outcome Measure
HIV-RNA <50 cop at week 96
HIV-RNA <400 and <50 cop/ml at week 48
Time to virological failure
Immunological efficacy at week 48 and 96 measured by absolute change from baseline in CD4 cell counts
Duration of change in CD4 cell count from baseline to >200,
Proportion of subjects experiencing one or more predefined values of fasting glucose and triglycerides, LDL and LDL/HDL ratio
Development of adverse events

Collaborators and Investigators

• Sponsor: Rijnstate Hospital
• Collaborators: GlaxoSmithKline
• Investigators: Principal Investigator: Clemens Richter, MD, Rijnstate Hospital, Arnhem, The Netherlands; Study Director: P. Mulder, Rijnstate Hospital, Arnhem, The Netherlands; Study Director: N. Langebeek, Rijnstate Hospital, Arnhem, The Netherlands; Study Director: D. N. Burger, Nijmegen, the Netherlands; Study Director: P. P. Koopmans, Nijmegen, the Netherlands; Study Director: C. H. ten Napel, Enschede, the Netherlands; Study Director: P. H. Groeneveld, Isala kliniek, Zwolle, the Netherlands; Study Director: H. G. Sprenger, Groningen, the Netherlands; Study Director: R. W. ten Kate, Haarlem, the Netherlands; Study Director: M. E. van Kasteren, Tilburg, the Netherlands; Study Director: J. D. Le grand, Charleroi, Belgium; Study Director: R. Vriesendorp, The Hague, the Netherlands; Study Director: B. Bravenboer, Eindhoven, the Netherlands; Study Director: I. M. Hoepelman, Utrecht, the Netherlands; Study Director: P. van Bentum, Rijnstate Hospital, Arnhem, The Netherlands; Study Director: A. Smit-den Baars, Rijnstate Hospital, Arnhem, The Netherlands

Study record dates

Study Major Dates

• Study Start: March 1, 2003
• Primary Completion (Actual): August 1, 2009
• Study Completion (Actual): September 1, 2009

Study Registration Dates

• First Submitted: November 29, 2006
• First Submitted That Met QC Criteria: November 29, 2006
• First Posted (Estimate): November 30, 2006

Study Record Updates

• Last Update Posted (Estimate): June 2, 2010
• Last Update Submitted That Met QC Criteria: May 31, 2010
• Last Verified: May 1, 2010

More Information

Terms related to this study

• Keywords: AIDS; Treatment Naive
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Lamivudine; Zidovudine; Abacavir
• Other Study ID Numbers: LTC-184-010403