- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01511809
Efficacy of Atazanavir/Ritonavir Monotherapy as Maintenance in Patients With Viral Suppression
Efficacy of Atazanavir / Ritonavir Monotherapy as Maintenance in Patients With Viral Suppression. Randomized, Open Label Non Inferiority Trial. A Phase 3 Study.
Study Overview
Status
Conditions
Intervention / Treatment
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
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
Lombardia
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Milan, Lombardia, Italy, 20127
- Infectious Diseases Department Fondazione Centro San Raffaele
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Atazanavir/ritonavir monotherapy
Patients will simplify therapy to ATV/RTV 300mg/100mg OD as monotherapy
|
Monotherapy Simplification Strategy with Atazanavir/ritonavir 300/100 mg once daily for 96 weeks.
Other Names:
|
No Intervention: Atazanavir/ritonavir triple therapy
Patients will continue the same regimen ATV/RTV 300mg/100mg OD plus 2 NRTIs as backbone
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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).
|
Up to week 48
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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. |
week 96
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Adriano Lazzarin, Professor, Ospedale San Raffaele
Publications and helpful links
General Publications
- Delfraissy JF, Flandre P, Delaugerre C, Ghosn J, Horban A, Girard PM, Norton M, Rouzioux C, Taburet AM, Cohen-Codar I, Van PN, Chauvin JP. Lopinavir/ritonavir monotherapy or plus zidovudine and lamivudine in antiretroviral-naive HIV-infected patients. AIDS. 2008 Jan 30;22(3):385-93. doi: 10.1097/QAD.0b013e3282f3f16d.
- Cameron DW, da Silva BA, Arribas JR, Myers RA, Bellos NC, Gilmore N, King MS, Bernstein BM, Brun SC, Hanna GJ. A 96-week comparison of lopinavir-ritonavir combination therapy followed by lopinavir-ritonavir monotherapy versus efavirenz combination therapy. J Infect Dis. 2008 Jul 15;198(2):234-40. doi: 10.1086/589622.
- Pulido F, Arribas JR, Delgado R, Cabrero E, Gonzalez-Garcia J, Perez-Elias MJ, Arranz A, Portilla J, Pasquau J, Iribarren JA, Rubio R, Norton M; OK04 Study Group. Lopinavir-ritonavir monotherapy versus lopinavir-ritonavir and two nucleosides for maintenance therapy of HIV. AIDS. 2008 Jan 11;22(2):F1-9. doi: 10.1097/QAD.0b013e3282f4243b.
- Arribas JR, Delgado R, Arranz A, Munoz R, Portilla J, Pasquau J, Perez-Elias MJ, Iribarren JA, Rubio R, Ocampo A, Sanchez-Conde M, Knobel H, Arazo P, Sanz J, Lopez-Aldeguer J, Montes ML, Pulido F; OK04 Study Group. Lopinavir-ritonavir monotherapy versus lopinavir-ritonavir and 2 nucleosides for maintenance therapy of HIV: 96-week analysis. J Acquir Immune Defic Syndr. 2009 Jun 1;51(2):147-52. doi: 10.1097/QAI.0b013e3181a56de5.
- Arribas JR, Horban A, Gerstoft J, Fatkenheuer G, Nelson M, Clumeck N, Pulido F, Hill A, van Delft Y, Stark T, Moecklinghoff C. The MONET trial: darunavir/ritonavir with or without nucleoside analogues, for patients with HIV RNA below 50 copies/ml. AIDS. 2010 Jan 16;24(2):223-30. doi: 10.1097/QAD.0b013e3283348944.
- Katlama C, Valantin MA, Algarte-Genin M, Duvivier C, Lambert-Niclot S, Girard PM, Molina JM, Hoen B, Pakianather S, Peytavin G, Marcelin AG, Flandre P. Efficacy of darunavir/ritonavir maintenance monotherapy in patients with HIV-1 viral suppression: a randomized open-label, noninferiority trial, MONOI-ANRS 136. AIDS. 2010 Sep 24;24(15):2365-74. doi: 10.1097/QAD.0b013e32833dec20.
- Swindells S, DiRienzo AG, Wilkin T, Fletcher CV, Margolis DM, Thal GD, Godfrey C, Bastow B, Ray MG, Wang H, Coombs RW, McKinnon J, Mellors JW; AIDS Clinical Trials Group 5201 Study Team. Regimen simplification to atazanavir-ritonavir alone as maintenance antiretroviral therapy after sustained virologic suppression. JAMA. 2006 Aug 16;296(7):806-14. doi: 10.1001/jama.296.7.806.
- Karlstrom O, Josephson F, Sonnerborg A. Early virologic rebound in a pilot trial of ritonavir-boosted atazanavir as maintenance monotherapy. J Acquir Immune Defic Syndr. 2007 Apr 1;44(4):417-22. doi: 10.1097/QAI.0b013e31802e2940.
- Wilkin TJ, McKinnon JE, DiRienzo AG, Mollan K, Fletcher CV, Margolis DM, Bastow B, Thal G, Woodward W, Godfrey C, Wiegand A, Maldarelli F, Palmer S, Coffin JM, Mellors JW, Swindells S. Regimen simplification to atazanavir-ritonavir alone as maintenance antiretroviral therapy: final 48-week clinical and virologic outcomes. J Infect Dis. 2009 Mar 15;199(6):866-71. doi: 10.1086/597119.
- Vernazza P, Daneel S, Schiffer V, Decosterd L, Fierz W, Klimkait T, Hoffmann M, Hirschel B. The role of compartment penetration in PI-monotherapy: the Atazanavir-Ritonavir Monomaintenance (ATARITMO) Trial. AIDS. 2007 Jun 19;21(10):1309-15. doi: 10.1097/QAD.0b013e32814e6b1c.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Anti-HIV Agents
- Anti-Retroviral Agents
- Protease Inhibitors
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 Enzyme Inhibitors
- HIV Protease Inhibitors
- Viral Protease Inhibitors
- Ritonavir
- Atazanavir Sulfate
Other Study ID Numbers
- MODAt
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