{ "FullStudy":{ "Rank":218171, "Study":{ "ProtocolSection":{ "IdentificationModule":{ "NCTId":"NCT01511809", "OrgStudyIdInfo":{ "OrgStudyId":"MODAt" }, "Organization":{ "OrgFullName":"Ospedale San Raffaele", "OrgClass":"OTHER" }, "BriefTitle":"Efficacy of Atazanavir/Ritonavir Monotherapy as Maintenance in Patients With Viral Suppression", "OfficialTitle":"Efficacy of Atazanavir / Ritonavir Monotherapy as Maintenance in Patients With Viral Suppression. Randomized, Open Label Non Inferiority Trial. A Phase 3 Study." }, "StatusModule":{ "StatusVerifiedDate":"January 2016", "OverallStatus":"Completed", "ExpandedAccessInfo":{ "HasExpandedAccess":"No" }, "StartDateStruct":{ "StartDate":"September 2010" }, "PrimaryCompletionDateStruct":{ "PrimaryCompletionDate":"July 2013", "PrimaryCompletionDateType":"Actual" }, "CompletionDateStruct":{ "CompletionDate":"May 2015", "CompletionDateType":"Actual" }, "StudyFirstSubmitDate":"January 13, 2012", "StudyFirstSubmitQCDate":"January 18, 2012", "StudyFirstPostDateStruct":{ "StudyFirstPostDate":"January 19, 2012", "StudyFirstPostDateType":"Estimate" }, "ResultsFirstSubmitDate":"November 7, 2014", "ResultsFirstSubmitQCDate":"November 17, 2014", "ResultsFirstPostDateStruct":{ "ResultsFirstPostDate":"November 24, 2014", "ResultsFirstPostDateType":"Estimate" }, "LastUpdateSubmitDate":"January 8, 2016", "LastUpdatePostDateStruct":{ "LastUpdatePostDate":"February 5, 2016", "LastUpdatePostDateType":"Estimate" } }, "SponsorCollaboratorsModule":{ "ResponsibleParty":{ "ResponsiblePartyType":"Principal Investigator", "ResponsiblePartyInvestigatorFullName":"Castagna Antonella", "ResponsiblePartyInvestigatorTitle":"Co- Investigator", "ResponsiblePartyInvestigatorAffiliation":"Ospedale San Raffaele" }, "LeadSponsor":{ "LeadSponsorName":"Ospedale San Raffaele", "LeadSponsorClass":"OTHER" }, "CollaboratorList":{ "Collaborator":[ { "CollaboratorName":"Bristol-Myers Squibb", "CollaboratorClass":"INDUSTRY" } ] } }, "OversightModule":{ "OversightHasDMC":"Yes" }, "DescriptionModule":{ "BriefSummary":"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.", "DetailedDescription":"This is a randomised (1:1), multicentre, comparative, parallel-group, prospective, open label, non-inferiority controlled clinical trial.\n\nEnrolled patients, taking an ATV/r based HAART and with stable HIV-RNA < 50c/ml (24 weeks), will be randomized to:\n\ncontinue the same regimen ATV/RTV 300mg/100mg OD plus 2 NRTIs (according to the specific dosing schedule) as backbone (HAART arm) with ATV/r\nor 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.\n\nPatients 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:\n\nclinical assessment.\nroutine 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.\n\nDuring follow-up, at randomization, week 48, week 96 or discontinuation, patients will additionally undergo:\n\nFat redistribution evaluation by DEXA (dual-energy X-ray absorptiometry\nVertebral and femoral bone mineral density evaluation by DEXA.\nECG;\nGlicate haemoglobin.\nAdherence assessment (questionnaire and/or pills counts).\nNeurocognitive evaluation [HIV-associated neurocognitive disorders (HANDs) evaluated by validated neuropsychological tests].\n\nIn 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." }, "ConditionsModule":{ "ConditionList":{ "Condition":[ "HIV-1 Infection" ] }, "KeywordList":{ "Keyword":[ "HIV-1" ] } }, "DesignModule":{ "StudyType":"Interventional", "PhaseList":{ "Phase":[ "Phase 3" ] }, "DesignInfo":{ "DesignAllocation":"Randomized", "DesignInterventionModel":"Parallel Assignment", "DesignPrimaryPurpose":"Treatment", "DesignMaskingInfo":{ "DesignMasking":"None (Open Label)" } }, "EnrollmentInfo":{ "EnrollmentCount":"117", "EnrollmentType":"Actual" } }, "ArmsInterventionsModule":{ "ArmGroupList":{ "ArmGroup":[ { "ArmGroupLabel":"Atazanavir/ritonavir monotherapy", "ArmGroupType":"Experimental", "ArmGroupDescription":"Patients will simplify therapy to ATV/RTV 300mg/100mg OD as monotherapy", "ArmGroupInterventionList":{ "ArmGroupInterventionName":[ "Drug: Atazanavir/ritonavir monotherapy" ] } },{ "ArmGroupLabel":"Atazanavir/ritonavir triple therapy", "ArmGroupType":"No Intervention", "ArmGroupDescription":"Patients will continue the same regimen ATV/RTV 300mg/100mg OD plus 2 NRTIs as backbone" } ] }, "InterventionList":{ "Intervention":[ { "InterventionType":"Drug", "InterventionName":"Atazanavir/ritonavir monotherapy", "InterventionDescription":"Monotherapy Simplification Strategy with Atazanavir/ritonavir 300/100 mg once daily for 96 weeks.", "InterventionArmGroupLabelList":{ "InterventionArmGroupLabel":[ "Atazanavir/ritonavir monotherapy" ] }, "InterventionOtherNameList":{ "InterventionOtherName":[ "ATV/r monotherapy" ] } } ] } }, "OutcomesModule":{ "PrimaryOutcomeList":{ "PrimaryOutcome":[ { "PrimaryOutcomeMeasure":"Proportion of Patients With Treatment Failure (TF)", "PrimaryOutcomeDescription":"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).", "PrimaryOutcomeTimeFrame":"Up to week 48" } ] }, "SecondaryOutcomeList":{ "SecondaryOutcome":[ { "SecondaryOutcomeMeasure":"Efficacy and Safety", "SecondaryOutcomeDescription":"Proportion of pts with confirmed virological and treatment failure at w96. Change in CD4 cell counts.\n\nOccurrence of viral resistance to atazanavir in pts with confirmed virologic failure.\n\nProportion of pts with adverse events, with ≥grade 2 adverse events or abnormal laboratory tests, proportion of pts with side effects leading to discontinuation.\n\nBody 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.", "SecondaryOutcomeTimeFrame":"week 96" } ] } }, "EligibilityModule":{ "EligibilityCriteria":"Inclusion Criteria:\n\nHIV infected patients\nage > 18 years\nOn treatment with ATV/r plus 2 NRTIs for at least 48 weeks\nVirological suppression (HIV-RNA<50 c/ml) by at least 24 weeks with ATV/r plus 2 NRTIs\nNo 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.\nCD4 cells nadir >100 cells/µL\nPPI 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.\n\nExclusion Criteria:\n\nPregnancy and breast feeding women\nAIDS defining events\nEvidence of active HBV infection (HBsAg positive)\nPrevious virological failure\nHistory of resistance to ATV\nUse of contraindicated medications", "HealthyVolunteers":"No", "Gender":"All", "MinimumAge":"18 Years", "MaximumAge":"90 Years", "StdAgeList":{ "StdAge":[ "Adult", "Older Adult" ] } }, "ContactsLocationsModule":{ "OverallOfficialList":{ "OverallOfficial":[ { "OverallOfficialName":"Adriano Lazzarin, Professor", "OverallOfficialAffiliation":"Ospedale San Raffaele", "OverallOfficialRole":"Principal Investigator" } ] }, "LocationList":{ "Location":[ { "LocationFacility":"Infectious Diseases Department Fondazione Centro San Raffaele", "LocationCity":"Milan", "LocationState":"Lombardia", "LocationZip":"20127", "LocationCountry":"Italy" } ] } }, "ReferencesModule":{ "ReferenceList":{ "Reference":[ { "ReferencePMID":"18195565", "ReferenceType":"background", "ReferenceCitation":"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." },{ "ReferencePMID":"18540803", "ReferenceType":"background", "ReferenceCitation":"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." },{ "ReferencePMID":"18097218", "ReferenceType":"background", "ReferenceCitation":"Pulido F, Arribas JR, Delgado R, Cabrero E, González-García J, Pérez-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." },{ "ReferencePMID":"19349870", "ReferenceType":"background", "ReferenceCitation":"Arribas JR, Delgado R, Arranz A, Muñoz R, Portilla J, Pasquau J, Pérez-Elias MJ, Iribarren JA, Rubio R, Ocampo A, Sánchez-Conde M, Knobel H, Arazo P, Sanz J, López-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." },{ "ReferencePMID":"20010070", "ReferenceType":"background", "ReferenceCitation":"Arribas JR, Horban A, Gerstoft J, Fätkenheuer 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." },{ "ReferencePMID":"20802297", "ReferenceType":"background", "ReferenceCitation":"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." },{ "ReferencePMID":"16905786", "ReferenceType":"background", "ReferenceCitation":"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." },{ "ReferencePMID":"17159658", "ReferenceType":"background", "ReferenceCitation":"Karlström O, Josephson F, Sönnerborg 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." },{ "ReferencePMID":"19191590", "ReferenceType":"background", "ReferenceCitation":"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." },{ "ReferencePMID":"17545707", "ReferenceType":"background", "ReferenceCitation":"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." } ] } } }, "ResultsSection":{ "ParticipantFlowModule":{ "FlowGroupList":{ "FlowGroup":[ { "FlowGroupId":"FG000", "FlowGroupTitle":"Atazanavir/Ritonavir Monotherapy", "FlowGroupDescription":"Patients will simplify therapy to ATV/RTV 300mg/100mg OD as monotherapy\n\nAtazanavir/ritonavir monotherapy: Monotherapy Simplification Strategy with Atazanavir/ritonavir 300/100 mg once daily for 96 weeks." },{ "FlowGroupId":"FG001", "FlowGroupTitle":"Atazanavir/Ritonavir Triple Therapy", "FlowGroupDescription":"Patients will continue the same regimen ATV/RTV 300mg/100mg OD plus 2 NRTIs as backbone" } ] }, "FlowPeriodList":{ "FlowPeriod":[ { "FlowPeriodTitle":"Overall Study", "FlowMilestoneList":{ "FlowMilestone":[ { "FlowMilestoneType":"STARTED", "FlowAchievementList":{ "FlowAchievement":[ { "FlowAchievementGroupId":"FG000", "FlowAchievementNumSubjects":"58" },{ "FlowAchievementGroupId":"FG001", "FlowAchievementNumSubjects":"59" } ] } },{ "FlowMilestoneType":"COMPLETED", "FlowAchievementList":{ "FlowAchievement":[ { "FlowAchievementGroupId":"FG000", "FlowAchievementNumSubjects":"51" },{ "FlowAchievementGroupId":"FG001", "FlowAchievementNumSubjects":"52" } ] } },{ "FlowMilestoneType":"NOT COMPLETED", "FlowAchievementList":{ "FlowAchievement":[ { "FlowAchievementGroupId":"FG000", "FlowAchievementNumSubjects":"7" },{ "FlowAchievementGroupId":"FG001", "FlowAchievementNumSubjects":"7" } ] } } ] } } ] } }, "BaselineCharacteristicsModule":{ "BaselineGroupList":{ "BaselineGroup":[ { "BaselineGroupId":"BG000", "BaselineGroupTitle":"Atazanavir/Ritonavir Monotherapy", "BaselineGroupDescription":"Patients will simplify therapy to ATV/RTV 300mg/100mg OD as monotherapy\n\nAtazanavir/ritonavir monotherapy: Monotherapy Simplification Strategy with Atazanavir/ritonavir 300/100 mg once daily for 96 weeks." },{ "BaselineGroupId":"BG001", "BaselineGroupTitle":"Atazanavir/Ritonavir Triple Therapy", "BaselineGroupDescription":"Patients will continue the same regimen ATV/RTV 300mg/100mg OD plus 2 NRTIs as backbone" },{ "BaselineGroupId":"BG002", "BaselineGroupTitle":"Total", "BaselineGroupDescription":"Total of all reporting groups" } ] }, "BaselineDenomList":{ "BaselineDenom":[ { "BaselineDenomUnits":"Participants", "BaselineDenomCountList":{ "BaselineDenomCount":[ { "BaselineDenomCountGroupId":"BG000", "BaselineDenomCountValue":"51" },{ "BaselineDenomCountGroupId":"BG001", "BaselineDenomCountValue":"52" },{ "BaselineDenomCountGroupId":"BG002", "BaselineDenomCountValue":"103" } ] } } ] }, "BaselineMeasureList":{ "BaselineMeasure":[ { "BaselineMeasureTitle":"Age, Continuous", "BaselineMeasureParamType":"Median", "BaselineMeasureDispersionType":"Inter-Quartile Range", "BaselineMeasureUnitOfMeasure":"years", "BaselineClassList":{ "BaselineClass":[ { "BaselineCategoryList":{ "BaselineCategory":[ { "BaselineMeasurementList":{ "BaselineMeasurement":[ { "BaselineMeasurementGroupId":"BG000", "BaselineMeasurementValue":"41.4", "BaselineMeasurementLowerLimit":"35.4", "BaselineMeasurementUpperLimit":"47.7" },{ "BaselineMeasurementGroupId":"BG001", "BaselineMeasurementValue":"41.7", "BaselineMeasurementLowerLimit":"36.6", "BaselineMeasurementUpperLimit":"49.8" },{ "BaselineMeasurementGroupId":"BG002", "BaselineMeasurementValue":"41.5", "BaselineMeasurementLowerLimit":"35.6", "BaselineMeasurementUpperLimit":"48" } ] } } ] } } ] } },{ "BaselineMeasureTitle":"Sex: Female, Male", "BaselineMeasureParamType":"Count of Participants", "BaselineMeasureUnitOfMeasure":"Participants", "BaselineClassList":{ "BaselineClass":[ { "BaselineCategoryList":{ "BaselineCategory":[ { "BaselineCategoryTitle":"Female", "BaselineMeasurementList":{ "BaselineMeasurement":[ { "BaselineMeasurementGroupId":"BG000", "BaselineMeasurementValue":"9" },{ "BaselineMeasurementGroupId":"BG001", "BaselineMeasurementValue":"7" },{ "BaselineMeasurementGroupId":"BG002", "BaselineMeasurementValue":"16" } ] } },{ "BaselineCategoryTitle":"Male", "BaselineMeasurementList":{ "BaselineMeasurement":[ { "BaselineMeasurementGroupId":"BG000", "BaselineMeasurementValue":"42" },{ "BaselineMeasurementGroupId":"BG001", "BaselineMeasurementValue":"45" },{ "BaselineMeasurementGroupId":"BG002", "BaselineMeasurementValue":"87" } ] } } ] } } ] } },{ "BaselineMeasureTitle":"Region of Enrollment", "BaselineMeasureParamType":"Number", "BaselineMeasureUnitOfMeasure":"participants", "BaselineClassList":{ "BaselineClass":[ { "BaselineClassTitle":"Italy", "BaselineCategoryList":{ "BaselineCategory":[ { "BaselineMeasurementList":{ "BaselineMeasurement":[ { "BaselineMeasurementGroupId":"BG000", "BaselineMeasurementValue":"51" },{ "BaselineMeasurementGroupId":"BG001", "BaselineMeasurementValue":"52" },{ "BaselineMeasurementGroupId":"BG002", "BaselineMeasurementValue":"103" } ] } } ] } } ] } },{ "BaselineMeasureTitle":"nadir CD4+", "BaselineMeasureDescription":"Lowest CD4+ value among those recorded since the first HIV positive test up to the start of MODAt study", "BaselineMeasureParamType":"Median", "BaselineMeasureDispersionType":"Inter-Quartile Range", "BaselineMeasureUnitOfMeasure":"cells/mm3", "BaselineClassList":{ "BaselineClass":[ { "BaselineCategoryList":{ "BaselineCategory":[ { "BaselineMeasurementList":{ "BaselineMeasurement":[ { "BaselineMeasurementGroupId":"BG000", "BaselineMeasurementValue":"274", "BaselineMeasurementLowerLimit":"221", "BaselineMeasurementUpperLimit":"355" },{ "BaselineMeasurementGroupId":"BG001", "BaselineMeasurementValue":"278", "BaselineMeasurementLowerLimit":"183", "BaselineMeasurementUpperLimit":"364" },{ "BaselineMeasurementGroupId":"BG002", "BaselineMeasurementValue":"276", "BaselineMeasurementLowerLimit":"211", "BaselineMeasurementUpperLimit":"361" } ] } } ] } } ] } },{ "BaselineMeasureTitle":"Years of antiretroviral treatment", "BaselineMeasureParamType":"Median", "BaselineMeasureDispersionType":"Inter-Quartile Range", "BaselineMeasureUnitOfMeasure":"years", "BaselineClassList":{ "BaselineClass":[ { "BaselineCategoryList":{ "BaselineCategory":[ { "BaselineMeasurementList":{ "BaselineMeasurement":[ { "BaselineMeasurementGroupId":"BG000", "BaselineMeasurementValue":"25", "BaselineMeasurementLowerLimit":"16", "BaselineMeasurementUpperLimit":"47" },{ "BaselineMeasurementGroupId":"BG001", "BaselineMeasurementValue":"25", "BaselineMeasurementLowerLimit":"18", "BaselineMeasurementUpperLimit":"54" },{ "BaselineMeasurementGroupId":"BG002", "BaselineMeasurementValue":"25", "BaselineMeasurementLowerLimit":"17", "BaselineMeasurementUpperLimit":"53" } ] } } ] } } ] } },{ "BaselineMeasureTitle":"HIV-1 RNA <50 copies/ml", "BaselineMeasureDescription":"Quantitative value of HIV-1 RNA copies/ml in plasma. HIV-1 RNA below 50 copies/ml (detection limit) is an indicator of efficacy of the antiretroviral therapy", "BaselineMeasureParamType":"Median", "BaselineMeasureDispersionType":"Inter-Quartile Range", "BaselineMeasureUnitOfMeasure":"months", "BaselineClassList":{ "BaselineClass":[ { "BaselineCategoryList":{ "BaselineCategory":[ { "BaselineMeasurementList":{ "BaselineMeasurement":[ { "BaselineMeasurementGroupId":"BG000", "BaselineMeasurementValue":"20", "BaselineMeasurementLowerLimit":"10", "BaselineMeasurementUpperLimit":"49" },{ "BaselineMeasurementGroupId":"BG001", "BaselineMeasurementValue":"18", "BaselineMeasurementLowerLimit":"12", "BaselineMeasurementUpperLimit":"49" },{ "BaselineMeasurementGroupId":"BG002", "BaselineMeasurementValue":"19", "BaselineMeasurementLowerLimit":"11", "BaselineMeasurementUpperLimit":"49" } ] } } ] } } ] } },{ "BaselineMeasureTitle":"HIV-RNA at ARV start", "BaselineMeasureParamType":"Median", "BaselineMeasureDispersionType":"Inter-Quartile Range", "BaselineMeasureUnitOfMeasure":"copies/mL", "BaselineClassList":{ "BaselineClass":[ { "BaselineCategoryList":{ "BaselineCategory":[ { "BaselineMeasurementList":{ "BaselineMeasurement":[ { "BaselineMeasurementGroupId":"BG000", "BaselineMeasurementValue":"79399", "BaselineMeasurementLowerLimit":"31046", "BaselineMeasurementUpperLimit":"183613" },{ "BaselineMeasurementGroupId":"BG001", "BaselineMeasurementValue":"42630", "BaselineMeasurementLowerLimit":"9696", "BaselineMeasurementUpperLimit":"123700" },{ "BaselineMeasurementGroupId":"BG002", "BaselineMeasurementValue":"59062", "BaselineMeasurementLowerLimit":"10834", "BaselineMeasurementUpperLimit":"165850" } ] } } ] } } ] } },{ "BaselineMeasureTitle":"CD4+", "BaselineMeasureParamType":"Median", "BaselineMeasureDispersionType":"Inter-Quartile Range", "BaselineMeasureUnitOfMeasure":"cells/mm3", "BaselineClassList":{ "BaselineClass":[ { "BaselineCategoryList":{ "BaselineCategory":[ { "BaselineMeasurementList":{ "BaselineMeasurement":[ { "BaselineMeasurementGroupId":"BG000", "BaselineMeasurementValue":"599", "BaselineMeasurementLowerLimit":"457", "BaselineMeasurementUpperLimit":"774" },{ "BaselineMeasurementGroupId":"BG001", "BaselineMeasurementValue":"570", "BaselineMeasurementLowerLimit":"417", "BaselineMeasurementUpperLimit":"735" },{ "BaselineMeasurementGroupId":"BG002", "BaselineMeasurementValue":"575", "BaselineMeasurementLowerLimit":"432", "BaselineMeasurementUpperLimit":"744" } ] } } ] } } ] } },{ "BaselineMeasureTitle":"HCV coinfection", "BaselineMeasureParamType":"Number", "BaselineMeasureUnitOfMeasure":"participants", "BaselineClassList":{ "BaselineClass":[ { "BaselineClassTitle":"Present", "BaselineCategoryList":{ "BaselineCategory":[ { "BaselineMeasurementList":{ "BaselineMeasurement":[ { "BaselineMeasurementGroupId":"BG000", "BaselineMeasurementValue":"11" },{ "BaselineMeasurementGroupId":"BG001", "BaselineMeasurementValue":"10" },{ "BaselineMeasurementGroupId":"BG002", "BaselineMeasurementValue":"21" } ] } } ] } },{ "BaselineClassTitle":"Absent", "BaselineCategoryList":{ "BaselineCategory":[ { "BaselineMeasurementList":{ "BaselineMeasurement":[ { "BaselineMeasurementGroupId":"BG000", "BaselineMeasurementValue":"40" },{ "BaselineMeasurementGroupId":"BG001", "BaselineMeasurementValue":"42" },{ "BaselineMeasurementGroupId":"BG002", "BaselineMeasurementValue":"82" } ] } } ] } } ] } } ] } }, "OutcomeMeasuresModule":{ "OutcomeMeasureList":{ "OutcomeMeasure":[ { "OutcomeMeasureType":"Primary", "OutcomeMeasureTitle":"Proportion of Patients With Treatment Failure (TF)", "OutcomeMeasureDescription":"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).", "OutcomeMeasureReportingStatus":"Posted", "OutcomeMeasureParamType":"Number", "OutcomeMeasureUnitOfMeasure":"percentage of patients", "OutcomeMeasureTimeFrame":"Up to week 48", "OutcomeGroupList":{ "OutcomeGroup":[ { "OutcomeGroupId":"OG000", "OutcomeGroupTitle":"Atazanavir/Ritonavir Monotherapy", "OutcomeGroupDescription":"Patients will simplify therapy to ATV/RTV 300mg/100mg OD as monotherapy\n\nAtazanavir/ritonavir monotherapy: Monotherapy Simplification Strategy with Atazanavir/ritonavir 300/100 mg once daily for 96 weeks." },{ "OutcomeGroupId":"OG001", "OutcomeGroupTitle":"Atazanavir/Ritonavir Triple Therapy", "OutcomeGroupDescription":"Patients will continue the same regimen ATV/RTV 300mg/100mg OD plus 2 NRTIs as backbone" } ] }, "OutcomeDenomList":{ "OutcomeDenom":[ { "OutcomeDenomUnits":"Participants", "OutcomeDenomCountList":{ "OutcomeDenomCount":[ { "OutcomeDenomCountGroupId":"OG000", "OutcomeDenomCountValue":"51" },{ "OutcomeDenomCountGroupId":"OG001", "OutcomeDenomCountValue":"52" } ] } } ] }, "OutcomeClassList":{ "OutcomeClass":[ { "OutcomeClassTitle":"ITT=Failure analysis", "OutcomeCategoryList":{ "OutcomeCategory":[ { "OutcomeMeasurementList":{ "OutcomeMeasurement":[ { "OutcomeMeasurementGroupId":"OG000", "OutcomeMeasurementValue":"27.5" },{ "OutcomeMeasurementGroupId":"OG001", "OutcomeMeasurementValue":"15.4" } ] } } ] } },{ "OutcomeClassTitle":"ITT=Success analysis", "OutcomeCategoryList":{ "OutcomeCategory":[ { "OutcomeMeasurementList":{ "OutcomeMeasurement":[ { "OutcomeMeasurementGroupId":"OG000", "OutcomeMeasurementValue":"7.9" },{ "OutcomeMeasurementGroupId":"OG001", "OutcomeMeasurementValue":"15.4" } ] } } ] } } ] }, "OutcomeAnalysisList":{ "OutcomeAnalysis":[ { "OutcomeAnalysisGroupIdList":{ "OutcomeAnalysisGroupId":[ "OG000", "OG001" ] }, "OutcomeAnalysisGroupDescription":"Here are reported the results of the 48-week interim analyses according to the intention-to-treat (ITT) principle. ITT=F (with re-intensification=failure) and the ITT=S (with re-intensification=success) treatment failure results are shown.\n\nBased on the efficacy data review, in June 2013, an independent Data and Safety Monitoring Board (DSMB) recommended to stop further patients’ enrolment and to follow-up the enrolled patients until 96 weeks, after having signed an updated informed consent.", "OutcomeAnalysisTestedNonInferiority":"Yes", "OutcomeAnalysisNonInferiorityType":"Non-Inferiority or Equivalence", "OutcomeAnalysisNonInferiorityComment":"A lower limit of the 95% confidence interval of the difference between the two proportions of treatment failure (triple therapy-monotherapy) below the pre-specified margin of non-inferiority of -10% established inferiority. A sample size of 342 patients (171 per treatment arm) provided 80% power (one-sided, alpha 0.05) to establish non-inferiority of ATV/r monotherapy as compared to ATV/r triple therapy with an overall treatment failure (TF) rate of 15% at week 48.", "OutcomeAnalysisParamType":"difference between TF proportions", "OutcomeAnalysisParamValue":"15", "OutcomeAnalysisCINumSides":"2-Sided" } ] } },{ "OutcomeMeasureType":"Secondary", "OutcomeMeasureTitle":"Efficacy and Safety", "OutcomeMeasureDescription":"Proportion of pts with confirmed virological and treatment failure at w96. Change in CD4 cell counts.\n\nOccurrence of viral resistance to atazanavir in pts with confirmed virologic failure.\n\nProportion of pts with adverse events, with ≥grade 2 adverse events or abnormal laboratory tests, proportion of pts with side effects leading to discontinuation.\n\nBody 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.", "OutcomeMeasureReportingStatus":"Not Posted", "OutcomeMeasureTimeFrame":"week 96" } ] } }, "AdverseEventsModule":{ "EventsFrequencyThreshold":"2", "EventsTimeFrame":"Up to week 48", "EventGroupList":{ "EventGroup":[ { "EventGroupId":"EG000", "EventGroupTitle":"Atazanavir/Ritonavir Monotherapy", "EventGroupDescription":"Patients will simplify therapy to ATV/RTV 300mg/100mg OD as monotherapy\n\nAtazanavir/ritonavir monotherapy: Monotherapy Simplification Strategy with Atazanavir/ritonavir 300/100 mg once daily for 96 weeks.", "EventGroupSeriousNumAffected":"2", "EventGroupSeriousNumAtRisk":"51", "EventGroupOtherNumAffected":"1", "EventGroupOtherNumAtRisk":"51" },{ "EventGroupId":"EG001", "EventGroupTitle":"Atazanavir/Ritonavir Triple Therapy", "EventGroupDescription":"Patients will continue the same regimen ATV/RTV 300mg/100mg OD plus 2 NRTIs as backbone", "EventGroupSeriousNumAffected":"0", "EventGroupSeriousNumAtRisk":"52", "EventGroupOtherNumAffected":"7", "EventGroupOtherNumAtRisk":"52" } ] }, "SeriousEventList":{ "SeriousEvent":[ { "SeriousEventTerm":"acute coronary stenosis", "SeriousEventOrganSystem":"Cardiac disorders", "SeriousEventAssessmentType":"Non-systematic Assessment", "SeriousEventStatsList":{ "SeriousEventStats":[ { "SeriousEventStatsGroupId":"EG000", "SeriousEventStatsNumAffected":"1", "SeriousEventStatsNumAtRisk":"51" },{ "SeriousEventStatsGroupId":"EG001", "SeriousEventStatsNumAffected":"0", "SeriousEventStatsNumAtRisk":"52" } ] } },{ "SeriousEventTerm":"left basal pneumonia", "SeriousEventOrganSystem":"Respiratory, thoracic and mediastinal disorders", "SeriousEventAssessmentType":"Non-systematic Assessment", "SeriousEventStatsList":{ "SeriousEventStats":[ { "SeriousEventStatsGroupId":"EG000", "SeriousEventStatsNumAffected":"1", "SeriousEventStatsNumAtRisk":"51" },{ "SeriousEventStatsGroupId":"EG001", "SeriousEventStatsNumAffected":"0", "SeriousEventStatsNumAtRisk":"52" } ] } } ] }, "OtherEventList":{ "OtherEvent":[ { "OtherEventTerm":"acute hepatitis", "OtherEventOrganSystem":"Hepatobiliary disorders", "OtherEventAssessmentType":"Non-systematic Assessment", "OtherEventStatsList":{ "OtherEventStats":[ { "OtherEventStatsGroupId":"EG000", "OtherEventStatsNumAffected":"1", "OtherEventStatsNumAtRisk":"51" },{ "OtherEventStatsGroupId":"EG001", "OtherEventStatsNumAffected":"1", "OtherEventStatsNumAtRisk":"52" } ] } },{ "OtherEventTerm":"nephrolitiasis", "OtherEventOrganSystem":"Renal and urinary disorders", "OtherEventAssessmentType":"Non-systematic Assessment", "OtherEventStatsList":{ "OtherEventStats":[ { "OtherEventStatsGroupId":"EG000", "OtherEventStatsNumAffected":"0", "OtherEventStatsNumAtRisk":"51" },{ "OtherEventStatsGroupId":"EG001", "OtherEventStatsNumAffected":"2", "OtherEventStatsNumAtRisk":"52" } ] } },{ "OtherEventTerm":"cholecystitis due to cholelithiasis", "OtherEventOrganSystem":"Hepatobiliary disorders", "OtherEventAssessmentType":"Non-systematic Assessment", "OtherEventStatsList":{ "OtherEventStats":[ { "OtherEventStatsGroupId":"EG000", "OtherEventStatsNumAffected":"0", "OtherEventStatsNumAtRisk":"51" },{ "OtherEventStatsGroupId":"EG001", "OtherEventStatsNumAffected":"1", "OtherEventStatsNumAtRisk":"52" } ] } },{ "OtherEventTerm":"hyperuricemia", "OtherEventOrganSystem":"Renal and urinary disorders", "OtherEventAssessmentType":"Non-systematic Assessment", "OtherEventStatsList":{ "OtherEventStats":[ { "OtherEventStatsGroupId":"EG000", "OtherEventStatsNumAffected":"0", "OtherEventStatsNumAtRisk":"51" },{ "OtherEventStatsGroupId":"EG001", "OtherEventStatsNumAffected":"1", "OtherEventStatsNumAtRisk":"52" } ] } },{ "OtherEventTerm":"gross haematuria with proteinuria", "OtherEventOrganSystem":"Renal and urinary disorders", "OtherEventAssessmentType":"Non-systematic Assessment", "OtherEventStatsList":{ "OtherEventStats":[ { "OtherEventStatsGroupId":"EG000", "OtherEventStatsNumAffected":"0", "OtherEventStatsNumAtRisk":"51" },{ "OtherEventStatsGroupId":"EG001", "OtherEventStatsNumAffected":"2", "OtherEventStatsNumAtRisk":"52" } ] } } ] } }, "MoreInfoModule":{ "CertainAgreement":{ "AgreementPISponsorEmployee":"No", "AgreementRestrictiveAgreement":"No" }, "PointOfContact":{ "PointOfContactTitle":"Dr. Antonella Castagna", "PointOfContactOrganization":"Ospedale San Raffaele", "PointOfContactEMail":"castagna.antonella1@hsr.it", "PointOfContactPhone":"00390226437934" } } }, "DerivedSection":{ "MiscInfoModule":{ "VersionHolder":"April 22, 2020" }, "InterventionBrowseModule":{ "InterventionMeshList":{ "InterventionMesh":[ { "InterventionMeshId":"D000019438", "InterventionMeshTerm":"Ritonavir" },{ "InterventionMeshId":"D000069446", "InterventionMeshTerm":"Atazanavir Sulfate" } ] }, "InterventionAncestorList":{ "InterventionAncestor":[ { "InterventionAncestorId":"D000017320", "InterventionAncestorTerm":"HIV Protease Inhibitors" },{ "InterventionAncestorId":"D000011480", "InterventionAncestorTerm":"Protease Inhibitors" },{ "InterventionAncestorId":"D000004791", "InterventionAncestorTerm":"Enzyme Inhibitors" },{ "InterventionAncestorId":"D000045504", "InterventionAncestorTerm":"Molecular Mechanisms of Pharmacological Action" },{ "InterventionAncestorId":"D000019380", "InterventionAncestorTerm":"Anti-HIV Agents" },{ "InterventionAncestorId":"D000044966", "InterventionAncestorTerm":"Anti-Retroviral Agents" },{ "InterventionAncestorId":"D000000998", "InterventionAncestorTerm":"Antiviral Agents" },{ "InterventionAncestorId":"D000000890", "InterventionAncestorTerm":"Anti-Infective Agents" },{ "InterventionAncestorId":"D000065692", "InterventionAncestorTerm":"Cytochrome P-450 CYP3A Inhibitors" },{ "InterventionAncestorId":"D000065607", "InterventionAncestorTerm":"Cytochrome P-450 Enzyme Inhibitors" } ] }, "InterventionBrowseLeafList":{ "InterventionBrowseLeaf":[ { "InterventionBrowseLeafId":"M19978", "InterventionBrowseLeafName":"Ritonavir", "InterventionBrowseLeafAsFound":"Ritonavir", "InterventionBrowseLeafRelevance":"high" },{ "InterventionBrowseLeafId":"M415", "InterventionBrowseLeafName":"Atazanavir Sulfate", "InterventionBrowseLeafAsFound":"Atazanavir", "InterventionBrowseLeafRelevance":"high" },{ "InterventionBrowseLeafId":"M12926", "InterventionBrowseLeafName":"Protease Inhibitors", "InterventionBrowseLeafRelevance":"low" },{ "InterventionBrowseLeafId":"M18192", "InterventionBrowseLeafName":"HIV Protease Inhibitors", "InterventionBrowseLeafRelevance":"low" },{ "InterventionBrowseLeafId":"M19934", "InterventionBrowseLeafName":"Anti-HIV Agents", "InterventionBrowseLeafRelevance":"low" },{ "InterventionBrowseLeafId":"M24015", "InterventionBrowseLeafName":"Anti-Retroviral Agents", "InterventionBrowseLeafRelevance":"low" },{ "InterventionBrowseLeafId":"M2895", "InterventionBrowseLeafName":"Antiviral Agents", "InterventionBrowseLeafRelevance":"low" },{ "InterventionBrowseLeafId":"M2795", "InterventionBrowseLeafName":"Anti-Infective Agents", "InterventionBrowseLeafRelevance":"low" },{ "InterventionBrowseLeafId":"M29151", "InterventionBrowseLeafName":"Cytochrome P-450 CYP3A Inhibitors", "InterventionBrowseLeafRelevance":"low" },{ "InterventionBrowseLeafId":"M29124", "InterventionBrowseLeafName":"Cytochrome P-450 Enzyme Inhibitors", "InterventionBrowseLeafRelevance":"low" } ] }, "InterventionBrowseBranchList":{ "InterventionBrowseBranch":[ { "InterventionBrowseBranchAbbrev":"Infe", "InterventionBrowseBranchName":"Anti-Infective Agents" },{ "InterventionBrowseBranchAbbrev":"All", "InterventionBrowseBranchName":"All Drugs and Chemicals" } ] } }, "ConditionBrowseModule":{ "ConditionBrowseLeafList":{ "ConditionBrowseLeaf":[ { "ConditionBrowseLeafId":"M8866", "ConditionBrowseLeafName":"Infection", "ConditionBrowseLeafRelevance":"low" },{ "ConditionBrowseLeafId":"M4951", "ConditionBrowseLeafName":"Communicable Diseases", "ConditionBrowseLeafRelevance":"low" },{ "ConditionBrowseLeafId":"M16833", "ConditionBrowseLeafName":"HIV Infections", "ConditionBrowseLeafRelevance":"low" },{ "ConditionBrowseLeafId":"M2103", "ConditionBrowseLeafName":"Acquired Immunodeficiency Syndrome", "ConditionBrowseLeafRelevance":"low" } ] }, "ConditionBrowseBranchList":{ "ConditionBrowseBranch":[ { "ConditionBrowseBranchAbbrev":"BC01", "ConditionBrowseBranchName":"Bacterial and Fungal Diseases" },{ "ConditionBrowseBranchAbbrev":"All", "ConditionBrowseBranchName":"All Conditions" },{ "ConditionBrowseBranchAbbrev":"BC02", "ConditionBrowseBranchName":"Viral Diseases" },{ "ConditionBrowseBranchAbbrev":"BC20", "ConditionBrowseBranchName":"Immune System Diseases" } ] } } } } } }