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IRIS
Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie.
Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial
Heerspink H. J. L.;Parving H. -H.;Andress D. L.;Bakris G.;Correa-Rotter R.;Hou F. -F.;Kitzman D. W.;Kohan D.;Makino H.;McMurray J. J. V.;Melnick J. Z.;Miller M. G.;Pergola P. E.;Perkovic V.;Tobe S.;Yi T.;Wigderson M.;de Zeeuw D.;Elbert A.;Vallejos A.;Alvarisqueta A.;Maffei L.;Juncos L.;de Arteaga J.;Greloni G.;Farias E.;Zucchini A.;Vogel D.;Cusumano A.;Santos J.;Fraenkel M.;Gallagher M.;Davis T.;Acharya S.;Cooke D.;Suranyi M.;Roger S.;Toussaint N.;Pollock C.;Chan D.;Stranks S.;MacIsaac R.;Endre Z.;Schmidt A.;Prager R.;Mayer G.;Warling X.;Jadoul M.;Hougardy J.;Vercammen C.;Van Vlem B.;Gillard P.;Costa e Forti A.;Borges J. L.;Santos Canani L.;Eliaschewitz F.;Leite S.;Fraige Filho F.;Paschoalin R.;Moura Neto J. A.;Deboni L.;de Lourdes Noronha I.;Cercato C.;Prompt C. A.;Zanella M.;Rassi N.;D'Avila D.;Milagres R.;Felicio J.;Pecoits Filho R.;Riella M. C.;Salles J.;Keitel E.;Draibe S.;Amodeo C.;Youmbissi J.;Roy L.;Cournoyer S.;Jolly S.;Pichette V.;Nesrallah G.;Bajaj H. S.;Khandwala H.;Aronson R.;Goluch R.;Tam P.;Rabbat C.;Bailey G.;Chow S.;Castillo A.;Danin Vargas A.;Gonzalez F.;Munoz R.;Gutierrez V.;Godoy G.;Zhao H.;Liu Z.;Zhao M.;Guo X.;Su B.;Fu S.;Xu Y.;Yang J.;Shi B.;Xiao G.;Shi W.;Hao C.;Xing C.;Hou F.;Luo Q.;Li Y.;Ji L.;Zuo L.;Wang S.;Ni Z.;Ding G.;Chen N.;Zhao J.;Jia W.;Yu S.;Weng J.;Xu G.;Fu P.;Sun S.;Liu B.;Ding X.;Rychlik I.;Oplustilova A.;Bartaskova D.;Honova V.;Chmelickova H.;Petr M.;Bucek P.;Tesar V.;Zahumensky E.;Povlsen J.;Egstrup K.;Oczachowska-Kulik A.;Rossing P.;Lahtela J.;Strand J.;Kantola I.;Petit C.;Combe C.;Zaoui P.;Esnault V.;Urena Torres P.;Halimi J. -M.;Dussol B.;Bieler T.;Budde K.;Dellanna F.;Segiet T.;Kosch C.;Schmidt-Guertler H.;Schenkenberger I.;Vielhauer V.;Pistrosch F.;Alscher M.;Hasslacher C.;Hugo C.;Muehlfeld A.;Wanner C.;Passadakis P.;Apostolou T.;Tentolouris N.;Stefanidis I.;Mavromatidis K.;Liakopoulos V.;Goumenos D.;Siamopoulos K.;Yeung V.;Ozaki R.;Fung S.;Tan K.;Tang S.;Lui S. L.;Cheung S. F.;Sreenan S.;Eustace J.;O'Shea D.;Lavin P.;Stack A.;Yagil Y.;Wainstein J.;Knobler H.;Cohen J.;Kenis I.;Daoud D.;Bar-Dayan Y.;Frajewicki V.;Adawi F.;Gesualdo L.;Santoro D.;Marino F.;Galfre A.;Brunati C.;Ruggenenti P.;Rombola G.;Pugliese G.;Ravera M.;Malberti F.;Pontoriero G.;Rampino T.;De Cosmo S.;Esposito C.;Nappi F.;Abaterusso C.;Conte G.;Panichi V.;Lauro D.;Capasso G.;Russo D.;Anzai J.;Naka M.;Ato K.;Tsujimoto T.;Nimura T.;Nakashima E.;Takeda T.;Fujii S.;Kobayashi K.;Iwaoka H.;Nagayama K.;Harada H.;Maeda H.;Kishimoto R.;Iitsuka T.;Itabashi N.;Furuya R.;Maeda Y.;Yamada D.;Sasaki N.;Sasaki H.;Ueda S.;Kashihara N.;Watanabe S.;Nakamura T.;Kanai H.;Makita Y.;Ono K.;Iehara N.;Goto D.;Kosuge K.;Tsuchida K.;Sato T.;Sekikawa T.;Okamoto H.;Tanaka T.;Ikeda N.;Tadika T.;Mukasa K.;Osonoi T.;Hirano F.;Nishimura M.;Yambe Y.;Tanaka Y.;Ujihara M.;Sakai T.;Imura M.;Umayahara Y.;Makino S.;Nakazawa J.;Yamaguchi Y.;Kashine S.;Miyaoka H.;Suzuki K.;Inoue T.;Nagai S.;Sato N.;Yamamoto M.;Taya N.;Fujita A.;Matsutani A.;Shibagaki Y.;Sato Y.;Yamauchi A.;Tsutsui M.;Ishiko T.;Kaneko S.;Azuma N.;Matsuda H.;Hashiguchi Y.;Onishi Y.;Tokui M.;Matsuhisa M.;Kiyosue A.;Shinoda J.;Ishikawa K.;Ahmad G.;Vijayasingham S.;Aziz N. A.;Hussein Z.;Fung Y. K.;Hassan W. H. H. W.;Wong H. S.;Goh B. L.;Ali N. M.;Merican N. S. Y. A.;Vaithilingam I.;Nik Ahmad N. N. F.;Adam N.;Sukor N.;Vengadasalam V. P. P.;Abdul Kadir K.;Mohamed M.;Renoirte Lopez K.;Leguizamo-Dimas A.;Chew Wong A.;Chevaile-Ramos J.;Gonzalez Gonzalez J.;Rico Hernandez R.;Nino-Cruz J.;Sauque Reyna L.;Gonzalez-Galvez G.;Madero Rovalo M.;Bochicchio-Ricardelli T.;Aldrete J.;Carranza-Madrigal J.;Vogt L.;Smak Gregoor P.;Barendregt J. N. M.;Luik P.;Gansevoort R.;Laverman G.;Pilmore H.;Lunt H.;Baker J.;Miller S.;Rabindranath K.;Zapata-Rincon L.;Vargas-Gonzales R.;Calderon Ticona J.;Dextre Espinoza A.;Burga Nunez J.;Zea-Nunez C. A.;Herrada Orue B.;Medina-Santander B.;Delgado-Butron C.;Farfan-Aspilcueta J.;Mazur S.;Necki M.;Wruk M.;Klodawska K.;Popenda G.;Skokowska E.;Arciszewska M.;Wiecek A.;Ciechanowski K.;Nowicki M.;Birne R.;Cabrita A.;Ramos A.;Antunes Ferreira M. A.;Matta Fontanet E.;Alcantara-Gonzalez A. A.;Comulada-Rivera A.;Galindo Ramos E.;Cangiano J.;Quesada-Suarez L.;Calderon Ortiz R.;Vazquez-Tanus J.;Burgos-Calderon R.;Rosado C.;Hancu N.;Pintilei E.;Mistodie C.;Bako G.;Ionutiu L.;Petrica L.;Timar R.;Tuta L.;Duma L.;Tutescu A.;Ivanova S.;Essaian A.;Zrazhevskiy K.;Tomilina N.;Smolyarchuk E.;Kuzin A.;Lantseva O.;Karpova I.;Shamkhalova M.;Liberanskaya N.;Yavdosyuk A.;Shvarts Y.;Bardymova T.;Blagoveshchenskaya O.;Solovev O.;Rechkova E.;Pikalova N.;Pavlova M.;Kolmakova E.;Sayfutdinov R.;Villevalde S.;Koziolova N.;Martynenko V.;Marasaev V.;Maksudova A.;Sigitova O.;Mordovin V.;Klimontov V.;Samoylova Y.;Karonova T.;Yeoh L. Y.;Teo B. W.;Foo M. W. Y.;Liew A.;Tkac I.;Oroszova A.;Fekete J.;Rosenberger J.;Obetkova I.;Fulopova A.;Kolesarova E.;Raslova K.;Smolko P.;Oksa A.;Distiller L.;Trokis J.;Adams L.;Makan H.;Ramlachan P.;Mitha E.;Coetzee K.;Punt Z.;Bhorat Q.;Naiker P.;Ellis G.;Van Zyl L.;Lee K. W.;Kim M. S.;Yoo S. -J.;Yoon K. H.;Cho Y. -W.;Park T. -S.;Kim S. Y.;Choi M. -G.;Oh T. K.;Lee K. -W.;Shon H. S.;Suh S. H.;Kim B. -J.;Doo-Man K.;Yi J. H.;Lee S. A.;Cho H. C.;Kim S. -G.;Cha D. -R.;Seo J. A.;Choi K. M.;Woo J. -T.;Ahn K. J.;Lee J. H.;Kim I. -J.;Lee M. -K.;Jang H. C.;Park K. -S.;Kim B. S.;Mok J. O.;Shin M.;Yoon S. A.;Nam-Goong I. -S.;Chung C. H.;Yu T. Y.;Lee H. W.;Soto Gonzalez A.;Almirall J.;Egido J.;Calero Gonzalez F.;Fernandez Fresnedo G.;Valera Cortes I.;Praga Terente M.;Garcia Mendez I.;Navarro Gonzalez J.;Herrero Calvo J.;Cigarran Guldris S.;Prieto Velasco M.;Minguela Pesquera J. I.;Galan A.;Pascual J.;Marques Vidas M.;Martins Munoz J.;Rodriguez-Perez J.;Castro-Alonso C.;Bonet Sol J.;Seron D.;Fernandez Giraldez E.;Arrieta Lezama J.;Montero N.;Hernandez-Jaras J.;Santamaria Olmo R.;Molas Coten J. R.;Hellberg O.;Fellstrom B.;Bock A.;Pei D.;Lin C. -L.;Tien K. -J.;Chen C. -C.;Huang C. -N.;Jiang J. -Y.;Wu D. -A.;Chu C. -H.;Tseng S. -T.;Chen J. -F.;Bau C. -T.;Sheu W.;Wu M. -S.;Sari R.;Sezer S.;Yildiz A.;Satman I.;Kalender B.;Mankovskyy B.;Fushtey I.;Stanislavchuk M.;Kolenyk M.;Dudar I.;Zolotaikina V.;Abrahamovych O.;Kostynenko T.;Petrosyan O.;Kuskalo P.;Galushchak O.;Legun O.;Topchii I.;Martynyuk L.;Stryzhak V.;Panina S.;Tkach S.;Korpachev V.;Maxwell P.;Gnudi L.;Kon S. P.;Tindall H.;Kalra P.;Mark P.;Patel D.;El-Shahawy M.;Bai L.;Nica R.;Lien Y. -H.;Menefee J.;Busch R.;Miller A.;Ahmed A.;Arif A.;Lee J.;Desai S.;Bansal S.;Bentsianov M.;Belledonne M.;Jere C.;Gaona R.;Greenwood G.;Brusco O.;Boiskin M.;Belo D.;Minasian R.;Atray N.;Lawrence M.;Taliercio J.;Pergola P.;Scott D.;Alvarez G.;Marder B.;Powell T.;Bakdash W.;Stoica G.;McFadden C.;Rendell M.;Wise J.;Jones A.;Jardula M.;Madu I. -J.;Varghese F.;Tulloch B.;Ahmed Z.;Hames M.;Nazeer I.;Shahid N.;John R.;Montero M.;Fitz-Patrick D.;Phillips L.;Guasch A.;Christofides E.;Gundroo A.;Amin M.;Bowman-Stroud C.;Link M.;Mulloy L.;Nammour M.;Lalwani T.;Hanson L.;Whaley-Connell A.;Herman L.;Chatha R.;Osama S.;Liss K.;Kayali Z.;Bhargava A.;Israel E.;Peguero-Rivera A.;Fang M.;Slover J.;Barengolts E.;Flores J.;Muoneke R.;Savin V.;Awua-Larbi S.;Levine A.;Newman G.;Golestaneh L.;Bohm G.;Reisin E.;Cruz L.;Weiss R.;Zieve F.;Horwitz E.;Chuang P.;Mersey J.;Manley J.;Graf R.;Bedros F.;Joshi S.;Frias J.;Assefi A.;O'Shaughnessy A.;Brantley R.;Minga T.;Tietjen D.;Kantor S.;Jamal A.;Guadiz R.;Hershon K.;Bressler P.;Kopyt N.;Cathcart H.;Bloom S.;Reichel R.;Nakhle S.;Dulude E.;Tarkan J.;Baker P.;Zeig S.;Moya Hechevarria J.;Ropero-Cartier A.;De la Calle G.;Doshi A.;Saba F.;Sligh T.;Shaw S.;Kumar J.;Szerlip H.;Bayliss G.;Perlman A.;Sakhrani L.;Gouge S.;Argoud G.;Acosta I.;Elder J.;Joshi S.;Sensenbrenner J.;Vicks S.;Mangoo-Karim R.;Galphin C.;Leon-Forero C.;Gilbert J.;Brown E.;Ijaz A.;Butt S.;Markell M.;Arauz-Pacheco C.;Sloan L.;Alvarado O.;Jabbour S.;Simon E.;Rastogi A.;James S.;Hall K.;Melish J.;Dixon B.;Adolphe A.;Kovesdy C.;Beddhu S.;Solomon R.;Fernando R.;Levin E.;Thakar C.;Robey B.;Goldfarb D.;Fried L.;Maddukuri G.;Thomson S.;Annand A.;Kronfli S.;Kalirao P.;Schmidt R.;Dahl N.;Blumenthal S.;Weinstein D.;Ostergaard O.;Weinstein T.;Ono Y.;Yalcin M.;Karim S.
2019-01-01
Abstract
Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11571/1323346
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simulazione ASN
Il report seguente simula gli indicatori relativi alla propria produzione scientifica in relazione alle soglie ASN 2023-2025 del proprio SC/SSD. Si ricorda che il superamento dei valori soglia (almeno 2 su 3) è requisito necessario ma non sufficiente al conseguimento dell'abilitazione. La simulazione si basa sui dati IRIS e sugli indicatori bibliometrici alla data indicata e non tiene conto di eventuali periodi di congedo obbligatorio, che in sede di domanda ASN danno diritto a incrementi percentuali dei valori. La simulazione può differire dall'esito di un’eventuale domanda ASN sia per errori di catalogazione e/o dati mancanti in IRIS, sia per la variabilità dei dati bibliometrici nel tempo. Si consideri che Anvur calcola i valori degli indicatori all'ultima data utile per la presentazione delle domande.
La presente simulazione è stata realizzata sulla base delle specifiche raccolte sul tavolo ER del Focus Group IRIS coordinato dall’Università di Modena e Reggio Emilia e delle regole riportate nel DM 589/2018 e allegata Tabella A. Cineca, l’Università di Modena e Reggio Emilia e il Focus Group IRIS non si assumono alcuna responsabilità in merito all’uso che il diretto interessato o terzi faranno della simulazione. Si specifica inoltre che la simulazione contiene calcoli effettuati con dati e algoritmi di pubblico dominio e deve quindi essere considerata come un mero ausilio al calcolo svolgibile manualmente o con strumenti equivalenti.
