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

This study is currently recruiting participants.

Verified January 2012 by Ospedale San Raffaele

Sponsor:

Collaborator:

Bristol-Myers Squibb

Information provided by (Responsible Party):

Castagna Antonella, Fondazione SanRaffaele del Monte Tabor

ClinicalTrials.gov Identifier:

NCT01511809

First received: January 13, 2012

Last updated: January 18, 2012

Last verified: January 2012

History of Changes

Tracking Information

First Received Date ^ICMJE

January 13, 2012

Last Updated Date

January 18, 2012

Start Date ^ICMJE

September 2010

Estimated Primary Completion Date

December 2013 (final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

HIV-RNA [ Time Frame: week 48 ] [ Designated as safety issue: No ]

Proportion of patients with confirmed virological failure (two consecutive measurements of HIV-RNA> 50 copies/ml)at week 48 in the two study arms.

Original Primary Outcome Measures ^ICMJE

Same as current

Change History

Complete list of historical versions of study NCT01511809 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures ^ICMJE

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.

Original Secondary Outcome Measures ^ICMJE

Same as current

Current Other Outcome Measures ^ICMJE

Not Provided

Original Other Outcome Measures ^ICMJE

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

Phase 3

Study Design ^ICMJE

Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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.

Study Arm (s)

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 300mg/100mg OD plus 2 NRTIs
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

Recruiting

Estimated Enrollment ^ICMJE

342

Estimated Completion Date

December 2015

Estimated Primary Completion Date

December 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

Gender

Both

Ages

18 Years to 90 Years

Accepts Healthy Volunteers

Contacts ^ICMJE

Contact: Adriano Lazzarin, Professor	0039022643 ext 7939	lazzarin.adriano@hsr.it
Contact: Antonella Castagna, MD	0039022643 ext 7934	castagna.antonella1@hsr.it

Location Countries ^ICMJE

Italy

Administrative Information

NCT Number ^ICMJE

NCT01511809

Other Study ID Numbers ^ICMJE

MODAt

Has Data Monitoring Committee

Yes

Responsible Party

Castagna Antonella, Fondazione SanRaffaele del Monte Tabor

Study Sponsor ^ICMJE

Ospedale San Raffaele

Collaborators ^ICMJE

Bristol-Myers Squibb

Investigators ^ICMJE

Principal Investigator:

Adriano Lazzarin, Professor

Ospedale San Raffaele

Information Provided By

Ospedale San Raffaele

Verification Date

January 2012

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

To Top