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

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ClinicalTrials.gov Identifier: NCT00324649
Recruitment Status : Completed
First Posted : May 11, 2006
Results First Posted : May 20, 2009
Last Update Posted : August 17, 2015
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Tracking Information
First Submitted Date  ICMJE May 9, 2006
First Posted Date  ICMJE May 11, 2006
Results First Submitted Date  ICMJE March 30, 2009
Results First Posted Date  ICMJE May 20, 2009
Last Update Posted Date August 17, 2015
Study Start Date  ICMJE May 2006
Actual Primary Completion Date March 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 22, 2013)
Change From Baseline in Limb Fat at Week 48 [ Time Frame: Baseline to Week 48 ]
Limb fat was measured by DEXA. Change = Week 48 value minus baseline value.
Original Primary Outcome Measures  ICMJE
 (submitted: May 9, 2006)
• Objective assessment: of change from baseline in limb fat at Week 48 as measured by DEXA.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 22, 2013)
  • Change From Baseline in the Mitochondrial DNA/Nuclear DNA Ratio (Oral Mucosa) [ Time Frame: Baseline to Week 48 ]
    Change = Week 48 value minus baseline value.
  • Change From Baseline in the Mitochondrial DNA/Nuclear DNA Ratio (Lymphocytes) [ Time Frame: Baseline to Week 48 ]
    Change = Week 48 value minus baseline value.
  • Change From Baseline in Lactate Concentration [ Time Frame: Baseline to Week 48 ]
    Change = Week 48 value minus baseline value.
  • Percentage of Days for Which Participants Were Compliant With Study Drug [ Time Frame: Baseline to Week 72 ]
    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 ]
  • Percentage of Participants With HIV-1 RNA > 50 and < 400 Copies/mL [ Time Frame: 48 weeks ]
  • Percentage of Participants With Virologic Failure [ Time Frame: 48 weeks ]
    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 ]
    Change = Week 48 value minus baseline value.
  • Change From Baseline in Fasting Serum Triglycerides [ Time Frame: Baseline to Week 48 ]
    Change = Week 48 value minus baseline value.
  • Change From Baseline in Fasting Total Cholesterol [ Time Frame: Baseline to Week 48 ]
    Change = Week 48 value minus baseline value.
  • Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL) [ Time Frame: Baseline to Week 48 ]
    Change = Week 48 value minus baseline value.
  • Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL) [ Time Frame: Baseline to Week 48 ]
    Change = Week 48 value minus baseline value.
  • Change From Baseline in Hemoglobin [ Time Frame: Baseline to Week 48 ]
    Change = Week 48 value minus baseline value.
  • Percent Change From Baseline in Hematocrit [ Time Frame: Baseline to Week 48 ]
    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 ]
    Change = Week 48 value minus baseline value.
  • Percentage of Participants With Any Adverse Event [ Time Frame: 72 weeks ]
    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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: May 9, 2006)
  • Change in the mitochondrial DNA/nuclear DNA ratio in the different visits compared with baseline.
  • Change in lactate concentration in the different visits compared with baseline.
  • Proportion of patients who maintain confirmed VIH-1 RNA levels of < 50 copies/mL.
  • Proportion of patients with HIV-1 RNA levels between >50 and <400 copies/mL.
  • Proportion of patients with virologic failure defines as confirmed with two consecutive HIV RNA >400 copies/mL.
  • Time to loss of virological response, defined as the time elapsed from the patient's first dose of study drug to confirmed HIV-1 RNA levels of > 50 and < 400 copies/mL, death caused by the disease, medication discontinuation, or addition of a new antire
  • Time to definite virological failure, defined as the time elapsed from the patient's first dose of study drug to confirmed HIV-1 RNA levels of > 400 copies/mL.
  • Change in CD4+ cell counts in the different study visits compared with baseline.
  • Change in serum triglycerides, total cholesterol, LDL, and HDL fractions in the different study visits compared with baseline.
  • Change in hemoglobin and hematocrit concentrations in the different visits compared with baseline.
  • Proportion of patients with different specific mutations after virological failure.
  • Proportion of patients who show treatment adherence (assessed according to SMQA questionnaire, see Appendix 10).
  • The following endpoints will be considered to asses tolerability after coding the adverse events:
  • Proportion of patients with any adverse event.
  • Proportion of patients for each adverse event.
  • Distribution of the intensity if each adverse event (the greatest intensity for each adverse event within a patient will be considered).
  • Distribution of the relationship between the adverse effect and the study drug (the strongest relation with the study drug for each adverse event within each patient will be considered).
  • Proportion of patients who discontinue the study prematurely (before week 48) due to adverse events.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Peripheral Body Fat Distribution After Switching Zidovudine and Lamivudine to Truvada
Official Title  ICMJE 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).
Brief Summary 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).
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).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE HIV-1
Intervention  ICMJE
  • Drug: Truvada
    Truvada once daily with continuation of the current NNRTI or PI at randomization.
  • Drug: Zidovudine/lamivudine
    Continuation of the zidovudine + lamivudine containing regimen plus the current NNRTI or PI at randomization.
Study Arms  ICMJE
  • Experimental: Truvada
    Truvada + NNRTI or PI.
    Intervention: Drug: Truvada
  • Active Comparator: Zidovudine/lamivudine
    Zidovudine/lamivudine + NNRTI or PI.
    Intervention: Drug: Zidovudine/lamivudine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 9, 2006)
80
Original Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE September 2008
Actual Primary Completion Date March 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00324649
Other Study ID Numbers  ICMJE GS-ES-164-0154
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Gilead Sciences
Study Sponsor  ICMJE Gilead Sciences
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pedro Ferrer Gilead Sciences, S.L.
PRS Account Gilead Sciences
Verification Date August 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP