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| Name | Class |
|---|---|
| Bristol-Myers Squibb | INDUSTRY |
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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.
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:
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:
During follow-up, at randomization, week 48, week 96 or discontinuation, patients will additionally undergo:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Atazanavir/ritonavir monotherapy | Experimental | Patients will simplify therapy to ATV/RTV 300mg/100mg OD as monotherapy |
|
| Atazanavir/ritonavir triple therapy | No Intervention | Patients will continue the same regimen ATV/RTV 300mg/100mg OD plus 2 NRTIs as backbone |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Atazanavir/ritonavir monotherapy | Drug | Monotherapy Simplification Strategy with Atazanavir/ritonavir 300/100 mg once daily for 96 weeks. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of Patients With Treatment Failure (TF) | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Efficacy and Safety | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Adriano Lazzarin, Professor | Ospedale San Raffaele | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Infectious Diseases Department Fondazione Centro San Raffaele | Milan | Lombardy | 20127 | Italy |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 18195565 | Background | 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. | |
| 18540803 |
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| ID | Title | Description |
|---|---|---|
| FG000 | Atazanavir/Ritonavir Monotherapy | Patients will simplify therapy to ATV/RTV 300mg/100mg OD as monotherapy Atazanavir/ritonavir monotherapy: Monotherapy Simplification Strategy with Atazanavir/ritonavir 300/100 mg once daily for 96 weeks. |
| FG001 | Atazanavir/Ritonavir Triple Therapy | Patients will continue the same regimen ATV/RTV 300mg/100mg OD plus 2 NRTIs as backbone |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Atazanavir/Ritonavir Monotherapy | Patients will simplify therapy to ATV/RTV 300mg/100mg OD as monotherapy Atazanavir/ritonavir monotherapy: Monotherapy Simplification Strategy with Atazanavir/ritonavir 300/100 mg once daily for 96 weeks. |
| BG001 | Atazanavir/Ritonavir Triple Therapy |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Proportion of Patients With Treatment Failure (TF) | 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). | Posted | Number | percentage of patients | Up to week 48 |
|
Up to week 48
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Atazanavir/Ritonavir Monotherapy | Patients will simplify therapy to ATV/RTV 300mg/100mg OD as monotherapy Atazanavir/ritonavir monotherapy: Monotherapy Simplification Strategy with Atazanavir/ritonavir 300/100 mg once daily for 96 weeks. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| acute coronary stenosis | Cardiac disorders | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| acute hepatitis | Hepatobiliary disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Antonella Castagna | Ospedale San Raffaele | 00390226437934 | castagna.antonella1@hsr.it |
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| ID | Term |
|---|---|
| D000069446 | Atazanavir Sulfate |
| ID | Term |
|---|---|
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D009842 | Oligopeptides |
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|
| week 96 |
| 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. |
| 18097218 | Background | 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. |
| 19349870 | Background | 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. |
| 20010070 | Background | 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. |
| 20802297 | Background | 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. |
| 16905786 | Background | 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. |
| 17159658 | Background | 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. |
| 19191590 | Background | 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. |
| 17545707 | Background | 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. |
Patients will continue the same regimen ATV/RTV 300mg/100mg OD plus 2 NRTIs as backbone |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| nadir CD4+ | Lowest CD4+ value among those recorded since the first HIV positive test up to the start of MODAt study | Median | Inter-Quartile Range | cells/mm3 |
|
| Years of antiretroviral treatment | Median | Inter-Quartile Range | years |
|
| HIV-1 RNA <50 copies/ml | 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 | Median | Inter-Quartile Range | months |
|
| HIV-RNA at ARV start | Median | Inter-Quartile Range | copies/mL |
|
| CD4+ | Median | Inter-Quartile Range | cells/mm3 |
|
| HCV coinfection | Number | participants |
|
Patients will simplify therapy to ATV/RTV 300mg/100mg OD as monotherapy Atazanavir/ritonavir monotherapy: Monotherapy Simplification Strategy with Atazanavir/ritonavir 300/100 mg once daily for 96 weeks. |
| OG001 | Atazanavir/Ritonavir Triple Therapy | Patients will continue the same regimen ATV/RTV 300mg/100mg OD plus 2 NRTIs as backbone |
|
|
|
| Secondary | Efficacy and Safety | 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. | Not Posted | week 96 | Participants |
| 2 |
| 51 |
| 1 |
| 51 |
| EG001 | Atazanavir/Ritonavir Triple Therapy | Patients will continue the same regimen ATV/RTV 300mg/100mg OD plus 2 NRTIs as backbone | 0 | 52 | 7 | 52 |
| left basal pneumonia | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| nephrolitiasis | Renal and urinary disorders | Non-systematic Assessment |
|
| cholecystitis due to cholelithiasis | Hepatobiliary disorders | Non-systematic Assessment |
|
| hyperuricemia | Renal and urinary disorders | Non-systematic Assessment |
|
| gross haematuria with proteinuria | Renal and urinary disorders | Non-systematic Assessment |
|
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| D010455 |
| Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |