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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Castagna Antonella, Ospedale San Raffaele
ClinicalTrials.gov Identifier:
NCT01511809
First received: January 13, 2012
Last updated: November 17, 2014
Last verified: November 2014
  Purpose

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.


Condition Intervention Phase
HIV-1 Infection
Drug: Atazanavir/ritonavir monotherapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Efficacy of Atazanavir / Ritonavir Monotherapy as Maintenance in Patients With Viral Suppression. Randomized, Open Label Non Inferiority Trial. A Phase 3 Study.

Resource links provided by NLM:


Further study details as provided by Ospedale San Raffaele:

Primary Outcome Measures:
  • Proportion of Patients With Treatment Failure (TF) [ Time Frame: Up to week 48 ] [ Designated as safety issue: No ]
    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).


Secondary Outcome Measures:
  • Efficacy and Safety [ Time Frame: week 96 ] [ Designated as safety issue: Yes ]

    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.



Enrollment: 117
Study Start Date: September 2010
Estimated Study Completion Date: December 2015
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Atazanavir/ritonavir monotherapy
Patients will simplify therapy to ATV/RTV 300mg/100mg OD as monotherapy
Drug: Atazanavir/ritonavir monotherapy
Monotherapy Simplification Strategy with Atazanavir/ritonavir 300/100 mg once daily for 96 weeks.
Other Name: ATV/r monotherapy
No Intervention: Atazanavir/ritonavir triple therapy
Patients will continue the same regimen ATV/RTV 300mg/100mg OD plus 2 NRTIs as backbone

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.

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT01511809

Locations
Italy
Infectious Diseases Department Fondazione Centro San Raffaele
Milan, Lombardia, Italy, 20127
Sponsors and Collaborators
Ospedale San Raffaele
Bristol-Myers Squibb
Investigators
Principal Investigator: Adriano Lazzarin, Professor Ospedale San Raffaele
  More Information

Publications:

Responsible Party: Castagna Antonella, Co- Investigator, Ospedale San Raffaele
ClinicalTrials.gov Identifier: NCT01511809     History of Changes
Other Study ID Numbers: MODAt
Study First Received: January 13, 2012
Results First Received: November 7, 2014
Last Updated: November 17, 2014
Health Authority: Italy: Ethics Committee

Keywords provided by Ospedale San Raffaele:
HIV-1

Additional relevant MeSH terms:
Atazanavir
Ritonavir
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
HIV Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protease Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014