Peripheral Body Fat Distribution After Switching Zidovudine and Lamivudine to Truvada (RECOMB)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT00324649
First received: May 9, 2006
Last updated: February 22, 2013
Last verified: February 2013
  Purpose

This study evaluated changes in body fat distribution in human immunodeficiency virus type 1 (HIV-1) infected participants who either switched from a zidovudine- plus lamivudine- containing highly active antiretroviral therapy (HAART) regimen to a regimen containing Truvada® (a fixed-dose combination tablet of emtricitabine [FTC, 200 mg] and tenofovir disoproxil fumarate [TDF, 300 mg]) or who remained on a zidovudine- plus lamivudine-containing regimen. Subjects continued their protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI).


Condition Intervention Phase
HIV-1
Drug: Truvada
Drug: Zidovudine/lamivudine
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: Pilot Phase IV, Multicenter, Randomized, Open-label and Controlled Study to Assess the Evolution of Peripheral Body Fat Distribution After Switching From Zidovudine Containing Backbone to Truvada in HIV-1-infected Patients on HAART (RECOMB Study).

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Change From Baseline in Limb Fat at Week 48 [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: Yes ]
    Limb fat was measured by DEXA. Change = Week 48 value minus baseline value.


Secondary Outcome Measures:
  • Change From Baseline in the Mitochondrial DNA/Nuclear DNA Ratio (Oral Mucosa) [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: Yes ]
    Change = Week 48 value minus baseline value.

  • Change From Baseline in the Mitochondrial DNA/Nuclear DNA Ratio (Lymphocytes) [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: Yes ]
    Change = Week 48 value minus baseline value.

  • Change From Baseline in Lactate Concentration [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: Yes ]
    Change = Week 48 value minus baseline value.

  • Percentage of Days for Which Participants Were Compliant With Study Drug [ Time Frame: Baseline to Week 72 ] [ Designated as safety issue: No ]
    Compliance = [1 - [(sum of days with a missed dose [per Question 6 study medication assessment questionnaire (SMAQ)])/(sum of days between SMAQ visits)]] *100 for visits with SMAQ data. An assessable visit is one where the number of missed days was reported [Question 6] and the number of days between SMAQ visits could be calculated.

  • Percentage of Participants Who Maintain Confirmed HIV-1 RNA < 50 Copies/mL [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Percentage of Participants With HIV-1 RNA > 50 and < 400 Copies/mL [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Percentage of Participants With Virologic Failure [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Virologic failure was defined as two consecutive HIV RNA values > 400 copies/mL.

  • Change From Baseline in Cluster Determinant 4 (CD4) Cell Count [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
    Change = Week 48 value minus baseline value.

  • Change From Baseline in Fasting Serum Triglycerides [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: Yes ]
    Change = Week 48 value minus baseline value.

  • Change From Baseline in Fasting Total Cholesterol [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: Yes ]
    Change = Week 48 value minus baseline value.

  • Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL) [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: Yes ]
    Change = Week 48 value minus baseline value.

  • Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL) [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: Yes ]
    Change = Week 48 value minus baseline value.

  • Change From Baseline in Hemoglobin [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: Yes ]
    Change = Week 48 value minus baseline value.

  • Percent Change From Baseline in Hematocrit [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: Yes ]
    Change = Week 48 value minus baseline value expressed as median percent change.

  • Change From Baseline in Waist Circumference/Hip Circumference Ratio [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: Yes ]
    Change = Week 48 value minus baseline value.

  • Percentage of Participants With Any Adverse Event [ Time Frame: 72 weeks ] [ Designated as safety issue: Yes ]

    Participants with treatment-emergent adverse events were analyzed. Adverse events were defined as any untoward medical occurrence in a clinical investigation subject administered a medicinal product and which did not necessarily have a causal relationship with study treatment, and were categorized using the Medical Dictionary for Regulatory Activities (MedDRA) Version 11.

    Treatment-emergent adverse events were events that met one of the following criteria:

    • Began or worsened in severity or relationship to study drug, on or after the date of the first dose of study drug and on or before the date of the last dose of study drug plus 30 days.
    • Had no recorded start date.

  • Percentage of Participants Who Discontinue the Study Prematurely (Before Week 48) Due to Adverse Events. [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 80
Study Start Date: May 2006
Study Completion Date: September 2008
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Truvada
Truvada + NNRTI or PI.
Drug: Truvada
Truvada once daily with continuation of the current NNRTI or PI at randomization.
Active Comparator: Zidovudine/lamivudine
Zidovudine/lamivudine + NNRTI or PI.
Drug: Zidovudine/lamivudine
Continuation of the zidovudine + lamivudine containing regimen plus the current NNRTI or PI at randomization.

Detailed Description:

Standard care for the treatment of HIV infection involves the use of a combination of three antiretroviral drugs. The initial recommended regimen in antiretroviral-naive patients according to therapeutic guidelines of the US Department of Health and Human Resources (DHHS) includes two nucleoside reverse transcriptase inhibitors (NRTIs) and a third drug from another class (PI or NRTI).

The use of nucleoside analogues, especially stavudine and zidovudine, is associated with untoward side effects, including lipodystrophy hepatic steatosis/lactic acidosis syndrome, peripheral neuropathy, and anemia. However, Truvada has a low potential for both mitochondrial toxicity and fat distribution disturbances.

As described in the Consensus Document of the Spanish Group for the Study of AIDS (GESIDA), and the AIDS National Plan from the Spanish Ministry of Health "Recommendations on metabolic alterations and body fat distribution", studies should focus on the evaluation of body fat disturbances after antiretroviral drug substitutions, based on the basic assumption of virologic control of the patient and equivalence in potency of the new drug regarding virological control. In addition, studies based on selective substitution of antiretroviral drugs in HIV-1 infected patients under virological control, are recommended in the European Medicines Agency (EMA) in the "Guideline on the clinical development of medicinal products for the treatment of HIV infection".

In this study, stable, virologically controlled, HIV-1 infected participants receiving antiretroviral regimens containing zidovudine and lamivudine were randomized to switch to Truvada or to stay on their zidovudine- plus lamivudine-containing regimen. Participants in both groups continued the third drug of their antiretroviral regimen (either an NNRTI or PI). Changes in limb fat in the two groups were assessed using dual-energy x-ray absorptiometry (DEXA).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV-1 infection documented by confirmed positive HIV-1 antibody test and/or positive polymerase chain reaction for HIV-1 ribonucleic acid (RNA).
  • Adult patients (over 18 years of age).
  • Current HAART regimen containing zidovudine + lamivudine at usual doses for at least 6 months.
  • Viral load < 50 copies/mL on the last two consecutive determinations, under zidovudine + lamivudine containing HAART regimen.
  • For women of childbearing potential, negative urine pregnancy test at screening visit.
  • Agreement to take part in the study and sign the informed consent.
  • Patients on lipid lowering treatment were allowed to participate in the study only if the lipid-lowering treatment (either statins or fibrates) was stable for at least 8 weeks prior to screening and it was not expected to change during the first 3 months of the study.

Exclusion Criteria:

  • Patients on current FTC or TDF therapy.
  • Patients with previous history of virological failure on an FTC or TDF-containing regimen.
  • Patients receiving a non-registered antiretroviral drug.
  • Patients receiving a triple-nucleoside antiretroviral combination.
  • Hypersensitivity to one of the components of the dosage forms of TDF or FTC, or previous history of intolerance to one of those drugs.
  • Known history of drug abuse or chronic alcohol consumption
  • Women who were pregnant or breast feeding, or female of childbearing potential who did not use an adequate method of contraception according to the investigator's judgment.
  • Active opportunistic infection or documented infection within the previous 4 weeks.
  • Documented active malignant disease (excluding Kaposi sarcoma limited to the skin).
  • Renal disease with creatinine clearance < 50 mL/min.
  • Concomitant use of nephrotoxic or immuno-suppressive drugs which could not be stopped without affecting the safety of the patient.
  • Receiving on-going therapy with systemic corticosteroids, Interleukin-2 or chemotherapy.
  • Patients who were not to be included in the study according to the investigator's criterion.
  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: NCT00324649

Locations
Spain
Gilead Sciences, S.L.
Madrid, Spain, E-28036
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Pedro Ferrer Gilead Sciences, S.L.
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT00324649     History of Changes
Other Study ID Numbers: GS-ES-164-0154
Study First Received: May 9, 2006
Results First Received: March 30, 2009
Last Updated: February 22, 2013
Health Authority: Spain: Spanish Agency of Medicines

Keywords provided by Gilead Sciences:
HIV-1

Additional relevant MeSH terms:
Zidovudine
Lamivudine
Lamivudine, zidovudine drug combination
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on July 29, 2014