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Efficacy of Atazanavir/Ritonavir Monotherapy as Maintenance in Patients With Viral Suppression

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01511809
Recruitment Status : Completed
First Posted : January 19, 2012
Results First Posted : November 24, 2014
Last Update Posted : February 5, 2016
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Castagna Antonella, Ospedale San Raffaele

Tracking Information
First Submitted Date  ICMJE January 13, 2012
First Posted Date  ICMJE January 19, 2012
Results First Submitted Date  ICMJE November 7, 2014
Results First Posted Date  ICMJE November 24, 2014
Last Update Posted Date February 5, 2016
Study Start Date  ICMJE September 2010
Actual Primary Completion Date July 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 17, 2014)
Proportion of Patients With Treatment Failure (TF) [ Time Frame: Up to week 48 ]
Proportion of patients with treatment failure defined as having one of the following events: confirmed viral rebound (CVR) or treatment discontinuation for any cause. CVR was established when 2 consecutive viral load values (HIV-1 RNA)>50 copies/mL occurred within 2 weeks during follow-up. In case of CVR, patients treated with atazanavir/ritonavir monotherapy had to re-introduce their previous 2NRTIs (re-intensification) and, if not suppressed (HIV-1 RNA <50 copies /ml) after 12 weeks, discontinued from the study. Re-intensification was considered as treatment failure in the primary analysis conducted according to the intention-to-treat principle (intention-to-treat analysis with re-intensification equal failure, ITT=Failure) while it was not in the secondary analysis (intention-to-treat analysis with re-intensification equal success, ITT=Success).
Original Primary Outcome Measures  ICMJE
 (submitted: January 18, 2012)
HIV-RNA [ Time Frame: week 48 ]
Proportion of patients with confirmed virological failure (two consecutive measurements of HIV-RNA> 50 copies/ml)at week 48 in the two study arms.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 18, 2012)
Efficacy and Safety [ Time Frame: week 96 ]
Proportion of pts with confirmed virological and treatment failure at w96. Change in CD4 cell counts. Occurrence of viral resistance to atazanavir in pts with confirmed virologic failure. Proportion of pts with adverse events, with ≥grade 2 adverse events or abnormal laboratory tests, proportion of pts with side effects leading to discontinuation. Body fat redistribution and vertebral and femoral bone mineral density. Adherence changes; changes in HIV-associated neurocognitive disorders. Difference in levels of activated Tcells and pro-inflammatory cytokines between treatment groups.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy of Atazanavir/Ritonavir Monotherapy as Maintenance in Patients With Viral Suppression
Official Title  ICMJE Efficacy of Atazanavir / Ritonavir Monotherapy as Maintenance in Patients With Viral Suppression. Randomized, Open Label Non Inferiority Trial. A Phase 3 Study.
Brief Summary The study will assess whether Atazanavir/ritonavir monotherapy provides a non-inferior proportion of virological efficacy with respect to ATV/RTV + 2 NRTIs in patients with stable suppressed viremia and no prior virologic failures.
Detailed Description

This is a randomised (1:1), multicentre, comparative, parallel-group, prospective, open label, non-inferiority controlled clinical trial.

Enrolled patients, taking an ATV/r based HAART and with stable HIV-RNA < 50c/ml (24 weeks), will be randomized to:

  • continue the same regimen ATV/RTV 300mg/100mg OD plus 2 NRTIs (according to the specific dosing schedule) as backbone (HAART arm) with ATV/r
  • or simplify therapy to ATV/RTV 300mg/100mg OD as monotherapy (Monotherapy arm) with ATV/r The study follow up will be 96 weeks after randomization and primary objective will be evaluated at week 48.

Patients will be followed every 4 weeks for the first 16 weeks, and then every 8 weeks until week 48, then every 12 weeks until week 96 or discontinuation ; at each visit the following evaluations will be performed:

  • clinical assessment.
  • routine laboratory tests (hematological tests and hematochemistry) including creatinine, phosphorus, calcium, alkaline phosphatase, gammaGT; urine analysis, lipid profile, level of HIV-RNA and CD4 cell counts.

During follow-up, at randomization, week 48, week 96 or discontinuation, patients will additionally undergo:

  • Fat redistribution evaluation by DEXA (dual-energy X-ray absorptiometry
  • Vertebral and femoral bone mineral density evaluation by DEXA.
  • ECG;
  • Glicate haemoglobin.
  • Adherence assessment (questionnaire and/or pills counts).
  • Neurocognitive evaluation [HIV-associated neurocognitive disorders (HANDs) evaluated by validated neuropsychological tests].

In case of viral rebound (defined as 2 consecutive measurement of HIV-RNA > 50 c/ml) patients will be immediately contacted in order to perform genotypic tests. Furthermore a plasma PK analysis will also be performed. Any patients with virological rebound will be selected for a reintensification therapy with NRTIs and if not suppressed after 12 weeks they will be discontinued.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE HIV-1 Infection
Intervention  ICMJE Drug: Atazanavir/ritonavir monotherapy
Monotherapy Simplification Strategy with Atazanavir/ritonavir 300/100 mg once daily for 96 weeks.
Other Name: ATV/r monotherapy
Study Arms  ICMJE
  • Experimental: Atazanavir/ritonavir monotherapy
    Patients will simplify therapy to ATV/RTV 300mg/100mg OD as monotherapy
    Intervention: Drug: Atazanavir/ritonavir monotherapy
  • No Intervention: Atazanavir/ritonavir triple therapy
    Patients will continue the same regimen ATV/RTV 300mg/100mg OD plus 2 NRTIs as backbone
Publications *

*   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: November 7, 2013)
117
Original Estimated Enrollment  ICMJE
 (submitted: January 18, 2012)
342
Actual Study Completion Date  ICMJE May 2015
Actual Primary Completion Date July 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • HIV infected patients
  • age > 18 years
  • On treatment with ATV/r plus 2 NRTIs for at least 48 weeks
  • Virological suppression (HIV-RNA<50 c/ml) by at least 24 weeks with ATV/r plus 2 NRTIs
  • No virologic failure after the initiation of the first antiretroviral therapy. Previous treatment changes due to toxicity or treatment simplifications will be permitted only if occurred with documented virological suppression.
  • CD4 cells nadir >100 cells/µL
  • PPI and H2-receptor antagonists as follows: the proton-pump inhibitors should not be used; if H2-receptor antagonists are co-administered, a dose equivalent to famotidine 20 mg BID should not be exceeded.

Exclusion Criteria:

  • Pregnancy and breast feeding women
  • AIDS defining events
  • Evidence of active HBV infection (HBsAg positive)
  • Previous virological failure
  • History of resistance to ATV
  • Use of contraindicated medications
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 90 Years   (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 Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01511809
Other Study ID Numbers  ICMJE MODAt
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Castagna Antonella, Ospedale San Raffaele
Study Sponsor  ICMJE Ospedale San Raffaele
Collaborators  ICMJE Bristol-Myers Squibb
Investigators  ICMJE
Principal Investigator: Adriano Lazzarin, Professor Ospedale San Raffaele
PRS Account Ospedale San Raffaele
Verification Date January 2016

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