Evaluation of the Efficacy and Safety Between Two Antiretroviral Regimens, in HIV-1-infected Treatment-naïve Subjects With Low CD4 Counts (DATA)

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified August 2013 by Institut de Médecine et d'Epidémiologie Appliquée - Fondation Internationale Léon M'Ba.
Recruitment status was:  Recruiting
Sponsor:
Information provided by (Responsible Party):
Institut de Médecine et d'Epidémiologie Appliquée - Fondation Internationale Léon M'Ba
ClinicalTrials.gov Identifier:
NCT01928407
First received: June 19, 2013
Last updated: August 20, 2013
Last verified: August 2013
  Purpose
A phase IV, prospective, multicenter , randomized open label, 48 weeks study to evaluate the antiretroviral efficacy and safety of atazanavir/ritonavir or darunavir/ritonavir, each in combination with a fixed dose of tenofovir disoproxil fumarate- emtricitabine in HIV-1-infected treatment-naïve subjects with CD4 counts below 200 µL.

Condition Intervention Phase
HIV-1 Infection
Immunosuppression-related Infectious Disease
Drug: DARUNAVIR
Drug: ATAZANAVIR
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase IV, Prospective, Multicenter , Randomized Open Label, 48 Weeks Study to Evaluate the Antiretroviral Efficacy and Safety of Atazanavir or Darunavir,Each in Combination With a Fixed Dose of Tenofovir Emtricitabine in HIV-1-infected Treatment-naïve Subjects With CD4counts Below 200 µL.

Resource links provided by NLM:


Further study details as provided by Institut de Médecine et d'Epidémiologie Appliquée - Fondation Internationale Léon M'Ba:

Primary Outcome Measures:
  • Viral load of HIV-1 < 50 cp/ml [ Time Frame: 48 weeks ]
    To evaluate the virological efficacy and safety at week 48 of 2 regimens atazanavir/ritonavir (ATZ/r) 300/100 mg or darunavir/ritonavir (DRV/r) 800/100 mg, each in combination with a fixed-dose of tenofovir/emtracitabine in HIV-1 treatment-naïve subjects with CD4 counts below 200 µL


Secondary Outcome Measures:
  • • Proportion of subjets with virologic efficacy [ Time Frame: 24 weeks ]
    • Proportion of subjets with virologic efficacy (viral load of HIV-1 <50 cp/ml)

  • • Proportion of subjects with confirmed virologic failure [ Time Frame: 24 weeks ]
    • Proportion of subjects with confirmed virologic failure (viral load > 50 cp/ml on 2 consecutive mesures)

  • Viral lod of HIV-1 on seminal fluid [ Time Frame: W00,W4 et W48 ]
    • Evaluate the viral load of HIV-1 at week 0, week 4 and week 48 on the seminal fluid (substudy)

  • Immunologic response [ Time Frame: W-4,W2,W4,W12,W24 and W48 ]
    • Evaluate the immunologic response by the CD4 mesearement at W-4,W2,W4,W12,W24 and W48

  • Differenciation and activation of lymphocytes [ Time Frame: W0,W2,W4,W12,W24 and W48 ]
    At the end of the study, in a central lab, we will measure some inflammation and activation markers (CD69, HLA-DR, CD38, annexine V, IL-6, CD14s, IL-7 plasma) of lymphocytes CD4 and CD8(with the plasmatheque collected during the study)

  • Pharmacokinetics evaluation of the drugs in plasma [ Time Frame: W4,W24 and W48 ]
    Measure of drugs (atazanir and darunavir) concentration (24 hours after taking treatment)in plasma at week 4, 24, and 48

  • Pharmacokinetic evaluation of the drugs in semen [ Time Frame: W4 and W48 ]
    Measure of drugs (atazanir and darunavir) concentration (24 hours after taking treatment)in semen at week 4 and 48

  • • Evaluate the relationship of bilirubinemia with atazanavir [ Time Frame: W4 and W48 ]
    Evaluate the relationship of the evolution of the measure of bilirubinemia (collected during study) with the concentration of atazanavir in blood

  • Fasting glucose, lipids and insulin [ Time Frame: W48 ]
    • Change from baseline in fasting lipids, fasting glucose and insulin over time in the 2 arms

  • Clinic and biologic tolerance [ Time Frame: W48 ]

    Evaluate the clinic and biologic tolerance between the 2 regimens (adverse event and some biologic measure will be collected for this evaluation).

    We will see in two arms if there are more adverse event or biological event.


  • Sexual behaviour [ Time Frame: W0,W24 et W48 ]
    • Compare sexual behaviour between the regimens (substudy with a questionnary)

  • Adherence patient satisfaction [ Time Frame: W2,W24 et W48 ]
    • Compare adherence patient satisfaction between the regimens (with questionnary)


Estimated Enrollment: 120
Study Start Date: March 2011
Estimated Study Completion Date: February 2014
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ATAZANAVIR
The patient included in this Group 1 will receive their first antiretroviral regimen included : ATV + TDF/FTC (or Abacavir/Lamivudine, [ABC/3TC], if contre indicated of TDF/FTC) The dose : atazanavir/ritonavir 300/100mg/day and TDF/FTC 245 /200 mg day, 3 pills once a day, during 48 weeks during a meal
Drug: ATAZANAVIR
The patient included will receive their first antiretroviral regimen included the atazanavir treatment in combination with 2 others molecules
Other Name: REYATAZ
Experimental: DARUNAVIR
The patients included in this Group 2 will receive their first antiretroviral regimen included Group 2 : DRV+ TDF/FTC (or ABC/3TC if contre-indicated of TDF/FTC) The dose : darunavir/ritonavir 800/100mg/day and TDF/FTC 245 /200 mg day, 4 pills once a day, during 48 weeks during a meal
Drug: DARUNAVIR
The patient included will receive their first antiretroviral regimen included the darunavir treatment in combination with 2 others molecules
Other Name: Prezista

  Hide Detailed Description

Detailed Description:

Principal objective

To evaluate the virological efficacy and safety at week 48 of 2 regimens atazanavir/ritonavir (ATZ/r) 300/100 mg or darunavir/ritonavir (DRV/r) 800/100 mg, each in combination with a fixed-dose of tenofovir/emtracitabine in HIV-1 treatment-naïve subjects with CD4 counts below 200 µL.

Secondary objectives

  • Proportion of subjets with virologic efficacy at week 24
  • Proportion of subjects with confirmed virologic failure at week 24 or later
  • Proportion of patients with virologic mutations
  • Evaluate the virologic effect in seminal fluid
  • To evaluate immunological response over time up to week 48
  • To assess plasma and seminal pharmacokinetics of the drugs in the treatment regimen at week 4, 24, and 48
  • Correlate the pharmacokinetic properties of the drugs with virologic outcome in plasma and semen at week 4 and 48
  • Correlate the free fraction (not bound to protein) of atazanavir and darunavir in plasma and semen to virologic outcome
  • Evaluate the relationship of bilirubinemia with atazanavir
  • Change from baseline in fasting lipids, fasting glucose and insulin over time in the 2 arms
  • Compare adherence patient satisfaction and sexual behaviour between the regimens

Methodology

This is a 48 week, multicentre, prospective, open label, phase IV, randomized. non comparative, study.

Inclusion criteria

  • Male or female, aged > 18 years of age.
  • HIV-1 infection determined by a positive ELISA and confirmed by Western blot
  • Plasma HIV-RNA > 1 000 c/mL
  • CD4+T cell count < =200 cells/mm3 at the time of screening, or < =250 cells/mm3 if the CD4 count was <200 cells/mm3 12 weeks before screening.
  • Women of childbearing potential must agree to use an effective method of barrier contraception or have documented sterility.
  • Subjects must have medical insurance throught the Securite Sociale
  • Ability to understand and provide written informed consent.

Non-inclusion criteria

  • Acute opportunistic infection within the past two weeks
  • HIV-2 infection
  • pregnant woman
  • Any subject with drug resistance mutations at screening
  • Any subject with a grade 3 or greater clinical or laboratory adverse event at screening
  • Any subject who has received antiretoviral therapy except for prevention of mother to child transmission and patients who has received post exposure prophylaxis for a a month or less
  • calculated creatinine clearance < 60/mL as estimated by the Cockcroft- Gault equation
  • Patients in the opinion of the investigator that are unlikley to be able to follow study instructions
  • Any subject unable to take antiretroviral medication for whatever reason
  • Any subject taking a treatment or medication that is contraindicated when co-administered with any arm or drug in the treatment.

Treatment:

  • Group 1 : ATV + TDF/FTC (or Abacavir/Lamivudine, [ABC/3TC], if TDF/FTc contre-indicated
  • atazanavir/ritonavir 300/100mg/day and TDF/FTC 245 /200 mg by day, 3 pills once a day, during 48 weeks during a meal
  • Group 2 : DRV+ TDF/FTC (or ABC/3TC if TDF/FTc contre-indicated)
  • darunavir/ritonavir 800/100mg/day and TDF/FTC 245 /200 mg by day, 4 pills once a day, during 48 weeks during a meal

Primary Endpoints :

  • Proportion of patients with HIV-1 plasma viral load below 50 copies/mL at week 48 while receiving their initial regimen
  • Proportion of patients experiencing grade 2-4 adverse clinical and laboratory events including hematology, chemistry, lipids (total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides), glucose and insulin by week 48.

Secondary endpoints:

  • Proportion of patients with plasma HIV RNA below 50 cp/mL at week 24
  • Proportion of patients with HIV RNA> 50 cp/mL at week 24 or later confirmed by a second HIV RNA at least 14 days after the first test
  • Development of resistance mutations in subjects who have virologic failure testing at 24 weeks or later tested by a genotypic resistance test
  • Evaluate the virologic effect in seminal fluid at baseline, W4 and W48 by change in HIV RNA concentrations in semen over time
  • To evaluate immunological response over time up to week 48 in the 2 arms by CD4 cell count ( W-4, W2,W4, W12, W36 and W48), differenciation and activation in T CD4 ( W2,W4, W12, W24 and W48); Change in lymphocyte subset reconsistution at week 48 compared to baseline. ; Change in immunolgic markers of inflammations at weeks 2, 4, 12, 24, 48
  • To assess plasma and seminal pharmacokinetics of the drugs in the treatment regimen at week 4, 24, and 48 through residual concentrations ( C min) of antiretroviral drugs at W4, W24, and W48
  • Atazanavir and darunavir (plasma and seminal) drug concentrations and coorelation with adverse clinical and laboratory events.
  • Evaluate the relationship of bilirubinemia with atazanavir pharmacokinetics (Cmin)
  • Evolution of lipid, glucose and insulin parameters from baseline to weeks 24 and 48
  • Adherence to regimen, patient satisfaction and sexual behaviour between the regimens at W2,W24 and W48 mesured by ( mettre ref)
  • Evolution of anthropomorphic measurements from baseline to weeks 24, 48.

Substudies Brief description (2 lines maximum) and person in charge of the substudy

  • Immunologic substudy ( Pr Brigitte Autran) : Change in immunolgic markers of inflammations at weeks 2, 4, 12, 24, 48 and change in lymphocyte subset reconsistution at week 48 compared to baseline.
  • Pharmacologic substudy ( Dr Gilles Peytavin) : To assess plasma and seminal pharmacokinetics of the drugs in the treatment regimen at week 4, 24, and 48 through residual concentrations ( C min) of antiretroviral drugs at W4, W24, and W48
  • Virologic substudy ( Dr Anne Geneviève Marcelin) : Evaluate the virologic effect in seminal fluid at baseline, W4 and W48
  • Behaviour substudy ( Dr France Lert) : Compare adherence patient satisfaction and sexual behaviour between the regimens at W2,W24 and W48

Estimated enrolment: 120 subjects (60 per group) randomly assigned 1:1

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • Male or female, aged > 18 years of age
  • HIV-1 infection determined by a positive ELISA and confirmed by Western blot
  • Plasma HIV-RNA > 1 000 c/mL
  • CD4+T cell count < =200 cells/mm3 at the time of screening, or < =250 cells/mm3 if the CD4 count was <200 cells/mm3 12 weeks before screening
  • Women of childbearing potential must agree to use an effective method of barrier contraception or have documented sterility
  • Subjects must have medical insurance throught the Securite Sociale
  • Ability to understand and provide written informed consent

Exclusion Criteria

  • Acute opportunistic infection within the past two weeks
  • HIV-2 infection
  • Pregnant woman
  • Any subject with drug resistance mutations at screening
  • Any subject with a grade 3 or greater clinical or laboratory adverse event at screening
  • Any subject who has received antiretoviral therapy except for prevention of mother to child transmission and patients who has received post exposure prophylaxis for a a month or less
  • Calculated creatinine clearance < 60/mL as estimated by the Cockcroft- Gault equation
  • Patients in the opinion of the investigator that are unlikley to be able to follow study instructions
  • Any subject unable to take antiretroviral medication for whatever reason
  • Any subject taking a treatment or medication that is contraindicated when co-administered with any arm or drug in the treatment
  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: NCT01928407

Locations
France
Hopital Zobda Quitman
Fort-de-france, Martinique, France, 97261
Centre Hospitalier D'Argenteuil
Argenteuil, France, 95107
Hopital Saint-Jacques
Besancon, France, 25000
Hopital Avicenne
Bobigny, France, 93000
Hopital Jean Verdier
Bondy, France, 93143
Hopital Saint-Andre
Bordeaux, France, 33075
Chu Cote de Nacre
Caen, France, 14033
Hopital Louis Mourier
Colombes, France, 92700
Hopital Le Bocage
Dijon, France, 21034
Hopital Raymond Poincare
Garches, France, 92380
C.H.D de Vendee
La Roche Sur Yon, France, 85925
Hopital Dupuytren
Limoges, France, 87000
Hopital Sainte-Marguerite
Marseille, France, 13274
Centre Hospitalier de Melun
Melun, France, 77011
Hopital L'Archet
Nice, France, 06202
Hopital Lariboisiere
Paris, France, 75010
Hopital Saint Antoine
Paris, France, 75012
Hopital Pitie-Salpetriere
Paris, France, 75013
Hopital Necker
Paris, France, 75015
Hopital Bichat
Paris, France, 75018
Hopital Tenon
Paris, France, 75020
Hopital Pitie-Salpetriere
Paris, France, 75651
Hopital Cochin
Paris, France, 75674
Hopital Europeen Georges Pompidou
Paris, France, 75908
Hopital Saint-Jean Roussillon
Perpignan, France, 66046
Hopital Rene Dubos
Pontoise, France, 95303
C.H.R.A
Pringy, France, 74374
Hopital Civil
Strasbourg, France, 67000
Hopital Gustave Dron
Tourcoing, France, 59208
Hopital Bretonneau
Tours, France, 37044
Sponsors and Collaborators
Institut de Médecine et d'Epidémiologie Appliquée - Fondation Internationale Léon M'Ba
Investigators
Principal Investigator: Laurence LS SLAMA, PhD Hospital TENON
Principal Investigator: Roland RL LANDMAN, PhD Institut de Médecine et d'Epidémiologie Appliquée - Fondation Internationale Léon M'Ba
  More Information

Responsible Party: Institut de Médecine et d'Epidémiologie Appliquée - Fondation Internationale Léon M'Ba
ClinicalTrials.gov Identifier: NCT01928407     History of Changes
Other Study ID Numbers: IMEA 040-DATA 
Study First Received: June 19, 2013
Last Updated: August 20, 2013

Keywords provided by Institut de Médecine et d'Epidémiologie Appliquée - Fondation Internationale Léon M'Ba:
naives, CD4 < 200 cell/mm3, Atazanavir, Darunavir

Additional relevant MeSH terms:
Communicable Diseases
Infection
Darunavir
Atazanavir Sulfate
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on January 24, 2017