A Bayesian reanalysis of the Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial
Authors: Zampieri Fernando G. , da Costa Bruno R. , Vaara Suvi T. , Lamontagne François , Rochwerg Bram , Nichol Alistair D. , McGuinness Shay , McAuley Danny F. , Ostermann Marlies , Wald Ron , Bagshaw Sean M. ,   STARRT-AKI Investigators, Bagshaw Sean M. , Wald Ron , Adhikari Neill K. J. , Bellomo Rinaldo , Dreyfuss Didier , Du Bin , Gallagher Martin P. , Gaudry Stéphane , Lamontagne François , Joannidis Michael , Liu Kathleen D. , McAuley Daniel F. , McGuinness Shay P. , Nichol Alistair D. , Ostermann Marlies , Palevsky Paul M. , Qiu Haibo , Pettilä Ville , Schneider Antoine G. , Smith Orla M. , Vaara Suvi , Weir Matthew , Bellomo Rinaldo , Eastwood Glenn M. , Peck Leah , Young Helen , Kruger Peter , Laurie Gordon , Saylor Emma , Meyer Jason , Venz Ellen , Wetzig Krista , French Craig , McGain Forbes , Mulder John , Fennessy Gerard , Koottayi Sathyajith , Bates Samantha , Towns Miriam , Morgan Rebecca , Tippett Anna , Udy Andrew , Mason Chris , Licari Elisa , Gantner Dashiell , McClure Jason , Nichol Alistair , McCracken Phoebe , Board Jasmin , Martin Emma , Vallance Shirley , Young Meredith , Vladic Chelsey , McGloughlin Steve , Gattas David , Buhr Heidi , Coles Jennifer , Hutch Debra , Wun James , Cole Louise , Whitehead Christina , Lowrey Julie , Masters Kristy , Gresham Rebecca , Campbell Victoria , Gutierrez David , Brailsford Jane , Forbes Loretta , Murray Lauren , Maguire Teena , NiChonghaile Martina , Orford Neil , Bone Allison , Elderkin Tania , Salerno Tania , Chimunda Tim , Fletcher Jason , Broadfield Emma , Porwal Sanjay , Knott Cameron , Boschert Catherine , Smith Julie , Richardson Angus , Hill Dianne , Duke Graeme , Oziemski Peter , Cegarra Santiago , Chan Peter , Welsh Deborah , Hunter Stephanie , Roodenburg Owen , Dyett John , Kokotsis Nicos , Moser Max , Yang Yang , Padayachee Laven , Vetro Joseph , Gangopadhyay Himangsu , Kaufman Melissa , Ghosh Angaj , Said Simone , Patel Alpesh , Bihari Shailesh , Matheson Elisha , Jin Xia , Shrestha Tapaswi , Schwartz Kate , Gallagher Martin P. , Cross Rosalba , Cheung Winston , Wong Helen , Kol Mark , Shah Asim , Wang Amanda Y. , Endre Zoltan , Bradford Celia , Janin Pierre , Finfer Simon , Diel Naomi , Gatward Jonathan , Hammond Naomi , Delaney Anthony , Bass Frances , Yarad Elizabeth , Buscher Hergen , Reynolds Claire , Baker Nerilee , Joannidis Michael , Bellmann Romuald , Peer Andreas , Hasslacher Julia , Koglberger Paul , Klein Sebastian , Zotter Klemens , Brandtner Anna , Finkenstedt Armin , Ditlbacher Adelheid , Hartig Frank , Fries Dietmar , Bachler Mirjam , Schenk Bettina , Wagner Martin , Eller Philipp , Staudinger Thomas , Tiller Esther , Schellongowski Peter , Bojic Andja , Hoste Eric A. , Bracke Stephanie , De Crop Luc , Vermeiren Daisy , Thome Fernando , Chiella Bianca , Fendt Lucia , Antunes Veronica , Lafrance Jean-Philippe , Lamontagne François , D’Aragon Frédérick , St-Arnaud Charles , Mayette Michael , Carbonnaeu Élaine , Marchand Joannie , Masse Marie-Hélène , Ladouceur Marilène , Turgeon Alexis F. , Lauzier François , Bellemare David , Francoeur Charles Langis , LeBlanc Guillaume , Guilbault Gabrielle , Grenier Stéphanie , Cloutier Eve , Boivin Annick , Delisle-Thibault Charles , Giannakouros Panagiota , Costerousse Olivier , Cailhier Jean-François , Carrier François-Martin , Ghamraoui Ali , Lebrasseur Martine , Benettaib Fatna , Salamé Maya , Boumahni Dounia , Sia Ying Tung , Naud Jean-François , Roy Isabelle , Stelfox Henry T. , Ruddell Stacey , Manns Braden J. , Duggan Shelley , Carney Dominic , Barchard Jennifer , Whitlock Richard P. , Belley-Cote Emilie , Savija Nevena , Sabev Alexandra , Campbell Troy , Creary Thais , Devereaux Kelson , Brodutch Shira , Rigatto Claudio , Paunovic Bojan , Mooney Owen , Glybina Anna , Harasemiw Oksana , Di Nella Michelle , Harmon John , Mehta Navdeep , Lakatos Louis , Haslam Nicole , Lellouche Francois , Simon Mathieu , Tung Ying , Lizotte Patricia , Bourchard Pierre-Alexandre , Rochwerg Bram , Karachi Tim , Millen Tina , Muscedere John , Maslove David , Gordon Boyd J. , Sibley Stephanie , Drover John , Hunt Miranda , Georgescu Ilinca , Wax Randy , Lenga Ilan , Sridhar Kavita , Steele Andrew , Fusco Kelly , Ghate Taneera , Tolibas Michael , Robinson Holly , Weir Matthew A. , Taneja Ravi , Ball Ian M. , Garg Amit , Campbell Eileen , Ovsenek Athena , Bagshaw Sean M. , van Diepen Sean , Baig Nadia , Magder Sheldon , Yao Han , Alam Ahsan , Campisi Josie , MacIntyre Erika , Rokosh Ella , Scherr Kimberly , Lapinsky Stephen , Mehta Sangeeta , Shah Sumesh , Niven Daniel J. , Stelfox Henry T. , Ruddell Stacey , Russell Michael , Jim Kym , Brown Gillian , Oxtoby Kerry , Hall Adam , Benoit Luc , Sokolowski Colleen , Prasad Bhanu , Rao Jag , Giebel Shelley , Kutsogiannis Demetrios J. , Thompson Patricia , Thompson Tayne , Cirone Robert , Kavikondala Kanthi , Soth Mark , Clarke France , Takaoka Alyson , Wald Ron , Mazer David , Burns Karen , Friedrich Jan , Klein David , Sandhu Gyan , Santos Marlene , Khalid Imrana , Hodder Jennifer , Dodek Peter , Ayas Najib , Alcuaz Victoria , Suen Gabriel , Rewa Oleksa , Singh Gurmeet , Norris Sean , Gibson Neil , Arias Castro , Shami Aysha , Pelletier Celine , Adhikari Neill K. J. , Zahirieh Alireza , Amaral Andre , Marinoff Nicole , Kaur Navjot , Perez Adic , Wang Jane , Haljan Gregory , Condin Christopher , McIntyre Lauralyn , Gomes Brigette , Porteous Rebecca , Watpool Irene , Hiremath Swapnil , Clark Edward , Herridge Margaret S. , Backhouse Felicity , Elizabeth Wilcox M. , Walczak Karolina , Ki Vincent , Sharman Asheer , Romano Martin , Bagshaw Sean M. , Noel Gibney R. T. , Romanovsky Adam S. , Rewa Oleksa , McCoshen Lorena , Baig Nadia , Wood Gordon , Ovakim Daniel , Auld Fiona , Carney Gayle , Duan Meili , Ji Xiaojun , Guo Dongchen , Qi Zhili , Lin Jin , Zhang Meng , Dong Lei , Liu Jingfeng , Liu Pei , Zhi Deyuan , Bai Guoqiang , Qiu Yu , Yang Ziqi , Bai Jing , Liu Zhuang , Zhuang Haizhou , Wang Haiman , Li Jian , Zhao Mengya , Zhou Xiao , Shi Xianqing , Ye Baning , Liu Manli , Wu Jing , Fu Yongjian , Long Dali , Pan Yu , Wang Jinlong , Mei Huaxian , Zhang Songsong , Wen Mingxiang , Yang Enyu , Mu Sijie , Li Jianquan , Hu Tingting , Qin Bingyu , Li Min , Wang Cunzhen , Dong Xin , Wang Kaiwu , Wang Haibo , Yang Jianxu , Du Bin , Wang Chuanyao , Wang Dongxin , Li Nan , Yu Zhui , Xu Song , Yao Lan , Hou Guo , Liu Zhou , Lu Liping , Lian Yingtao , Wang Chunting , Zhang Jichen , Ding Ruiqi , Qi Guoqing , Wang Qizhi , Wang Peng , Meng Zhaoli , Chen Man , Hu Xiaobo , He Xiandi , Zhao Shibing , Hang Lele , Li Rui , Qin Suhui , Lu Kun , Dun Shijuan , Liu Cheng , Zhou Qi , Chen Zhenzhen , Mei Jing , Zhang Minwei , Xu Hao , Lin Jincan , Shi Qindong , Fu Lijuan , Zeng Qinjing , Ma Hongye , Yan Jinqi , Gao Lan , Liu Hongjuan , Zhang Lei , Li Hao , He Xiaona , Fan Jingqun , Guo Litao , Liu Yu , Wang Xue , Sun Jingjing , Liu Zhongmin , Yang Juan , Ding Lili , Sheng Lulu , Liu Xingang , Yan Jie , Wang Quihui , Wang Yifeng , Zhao Dan , Zhao Shuangping , Hu Chenghuan , Li Jing , Deng Fuxing , Qui Haibo , Yang Yi , Mo Min , Pan Chun , Wu Changde , Huang Yingzi , Huang Lili , Liu Airan , Pettilä Ville , Vaara Suvi T. , Korhonen Anna-Maija , Törnblom Sanna , Sutinen Sari , Pettilä Leena , Heinonen Jonna , Lappi Eliria , Suhonen Taria , Karlsson Sari , Hoppu Sanna , Jalkanen Ville , Kuitunen Anne , Levoranta Markus , Långsjö Jaakko , Ristimäki Sanna , Malila Kaisa , Wootten Anna , Varila Simo , Järvisalo Mikko J. , Inkinen Outi , Kentala Satu , Leivo Keijo , Haltia Paivi , Dreyfuss Didier , Ricard Jean-Damien , Messika Jonathan , Tiagarajah Abirami , Emery Malo , Dechanet Aline , Gernez Coralie , Roux Damien , Martin-Lefevre Laurent , Fiancette Maud , Vinatier Isabelle , Lacherade Jean Claude , Colin Gwenhaël , Lebert Christine , Azais Marie-Ange , Yehia Aihem , Pouplet Caroline , Lagarrigue Matthieu Henry- , Seguin Amélie , Crosby Laura , Maizel Julien , Titeca-Beauport Dimitri , Combes Alain , Nieszkowska Ania , Masi Paul , Demoule Alexandre , Mayaux Julien , Dres Martin , Morawiec Elise , Decalvele Maxens , Demiri Suela , Faure Morgane , Marios Clémence , Mallet Maxime , Ordon Marie Amélie , Morizot Laura , Cantien Marie , Pousset François , Gaudry Stéphane , Poirson Florent , Cohen Yves , Argaud Laurent , Cour Martin , Bitker Laurent , Simon Marie , Hernu Romain , Baudry Thomas , De La Salle Sylvie , Robine Adrien , Sedillot Nicholas , Tchenio Xavier , Bouisse Camille , Roux Sylvie , Barbar Saber Davide , Trusson Rémi , Tamion Fabienne , Grangé Steven , Carpentier Dorothée , Chevrel Guillaume , Ensenyat-Martin Luis , Marque 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Fadel Fouad , Cleophax Cedric , Dufour Nicolas , Grant Caroline , Thuong Marie , Reignier Jean , Canet Emmanuel , Nicolet Laurent , Boulain Thierry , Nay Mai-Anh , Benzekri Dalila , Barbier François , Bretagnol Anne , Kamel Toufik , Mathonnet Armelle , Muller Grégoire , Skarzynski Marie , Rossi Julie , Pradet Amandine , Dos Santos Sandra , Guery Aurore , Muller Lucie , Felix Luis , Bohé Julien , Thiéry Guillaume , Aissaoui Nadia , Vimpere Damien , Commeureuc Morgane , Diehl Jean-Luc , Guerot Emmanuel , Liangos Orfeas , Wittig Monika , Zarbock Alexander , Küllmar Mira , van Waegeningh Thomas , Rosenow Nadine , Nichol Alistair D. , Brickell Kathy , Doran Peter , Murray Patrick T. , Landoni Giovanni , Lembo Rosalba , Zangrillo Alberto , Monti Giacomo , Tozzi Margherita , Marzaroli Matteo , Lombardi Gaetano , Paternoster Gianluca , Vitiello Michelangelo , McGuinness Shay , Parke Rachael , Butler Magdalena , Gilder Eileen , Cowdrey Keri-Anne , Wallace Samantha , Hallion Jane , Woolett Melissa , Neal Philippa , Duffy Karina , Long Stephanie , McArthur Colin , Simmonds Catherine , Chen Yan , McConnochie Rachael , Newby Lynette , Knight David , Henderson Seton , Mehrtens Jan , Morgan Stacey , Morris Anna , Vander Hayden Kymbalee , Burke Tara , Bailey Matthew , Freebairn Ross , Chadwick Lesley , Park Penelope , Rolls Christine , Thomas Liz , Buehner Ulrike , Williams Erin , Albrett Jonathan , Kirkham Simon , Jackson Carolyn , Browne Troy , Goodson Jennifer , Jackson David , Houghton James , Callender Owen , Higson Vicki , Keet Owen , Dominy Clive , Young Paul , Hunt Anna , Judd Harriet , Lawrence Cassie , Olatunji Shaanti , Robertson Yvonne , Latimer-Bell Charlotte , Hendry Deborah , Mckay-Vucago Agnes , Beehre Nina , Lesona Eden , Navarra Leanlove , Robinson Chelsea , Jang Ryan , Junge Andrea , Lambert Bridget , Schneider Antoine G. , Thibault Michel , Eckert Philippe , Kissling Sébastien , Polychronopoulos Erietta , Poli Elettra , Altarelli Marco , Schnorf Madeleine , Mallaird Samia Abed , Heidegger Claudia , Perret Aurelie , Montillier Philippe , Sangla Frederic , Neils Seigenthaller , De Watteville Aude , Phull Mandeep-Kaur , George Aparna , Hussain Nauman , Pogreban Tatiana , Lobaz Steve , Daniels Alison , Cunningham Mishell , Kerr Deborah , Nicholson Alice , Shanmugasundaram Pradeep , Abrams Judith , Manso Katarina , Hambrook Geraldine , McKerrow Elizabeth , Salva Juvy , Foulkes Stephen , Wise Matthew , Morgan Matt , Brooks Jenny , Cole Jade , Davies Tracy Michelle , Hill Helen , Thomas Emma , Vizcaychipi Marcela , Baharlo Behrad , Carungcong Jaime , Costa Patricia , Martins Laura , Kapoor Ritoo , Hazelton Tracy , Moon Angela , Musselwhite Janine , Shelley Ben , McCall Philip , Ostermann Marlies , Arbane Gill , Bociek Aneta , Marotti Martina , Lim Rosario , Campos Sara , Novellas Neus Grau , Cennamo Armando , Slack Andrew , Wyncoll Duncan , Camporota Luigi , Sparkes Simon , Tilley Rosalinde , Rattray Austin , Moreland Gayle , Duffy Jane , McGonigal Elizabeth , Hopkins Philip , Finney Clare , Smith John , Noble Harriet , Watson Hayley , Harris Claire-Louise , Clarey Emma , Corcoran Eleanor , Beck James , Howcroft Clare , Youngs Nora , Wilby Elizabeth , Ogg Bethan , Wolverson Adam , Lee Sandra , Butler Susie , Okubanjo Maryanne , Hindle Julia , Welters Ingeborg , Williams Karen , Johnson Emily , Patrick-Heselton Julie , Shaw David , Waugh Victoria , Stewart Richard , Mwaura Esther , Wren Lynn , Mew Louise , Sutherland Sara-Beth , Adderley Jane , Ruddy Jim , Harkins Margaret , Kaye Callum , Scott Teresa , Mitchell Wendy , Anderson Felicity , Willox Fiona , Jagannathan Vijay , Clark Michele , Purv Sarah , Sharman Andrew , Meredith Megan , Ryan Lucy , Conner Louise , Peters Cecilia , Harvey Dan , Roshdy Ashraf , Collins Amy , Sim Malcolm , Henderson Steven , Chee Nigel , Pitts Sally , Bowman Katie , Dilawershah Maria , Vamplew Luke , Howe Elizabeth , Rogers Paula , Hernandez Clara , Prendergast Clara , Benton Jane , Rosenberg Alex , Forni Lui G. , Grant Alice , Carvelli Paula , Raithatha Ajay , Bird Sarah , Richardson Max , Needham Matthew , Hirst Claire , Ball Jonathan , Leaver Susannah , Howlett Luisa , Delgado Carlos Castro , Farnell-Ward Sarah , Farrah Helen , Gray Geraldine , Joseph Gipsy , Robinson Francesca , Tridente Ascanio , Harrop Clare , Shuker Karen , McLaughlan Derek , Ramsey Judith , Meehan Sharon , Rose Bernd Oliver , Reece-Anthony Rosie , Gurung Babita , Whitehouse Tony , Snelson Catherine , Veenith Tonny , Johnston Andy , Cooper Lauren , Carrera Ron , Ellis Karen , Fellows Emma , Harkett Samanth , Bergin Colin , Spruce Elaine , Despy Liesl , Goundry Stephanie , Dooley Natalie , Mason Tracy , Clark Amy , Dignam Gemma , Ward Geraldine , Attwood Ben , Parsons Penny , Mason Sophie , Margarson Michael , Lord Jenny , McGlone Philip , Hodgson Luke E. , Chadbourn Indra , Gomez Raquel , Margalef Jordi , Pretorius Rinus , Hamshere Alexandra , Carter Joseph , Cahill Hazel , Grainger Lia , Howard Kate , Forshaw Greg , Guy Zoe , Kashani Kianoush B. , Albright Robert C. , Amsbaugh Amy , Stoltenberg Anita , Niven Alexander S. , Lynch Matthew , O’Mara AnnMarie , Naeem Syed , Sharif Sairah , Goulart Joyce McKenney , Lynch Matthew , O’Mara AnnMarie , Naeem Syed , Sharif Sairah , Goulart Joyce McKenney , Tolwani Ashita , Lyas Claretha , Latta Laura , Bihorac Azra , Hashemighouchani Haleh , Efron Philip , Ruppert Matthew , Cupka Julie , Kiley Sean , Carson Joshua , White Peggy , Omalay George , Brown Sherry , Velez Laura , Marceron Alina , Neyra Javier A. , Aycinena Juan Carlos , Elias Madona , Ortiz-Soriano Victor M. , Hauschild Caroline , Dorfman Robert 
Published: August 2022

Abstract
Background
Timing of initiation of kidney-replacement therapy (KRT) in critically ill patients remains controversial. The Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial compared two strategies of KRT initiation (accelerated versus standard) in critically ill patients with acute kidney injury and found neutral results for 90-day all-cause mortality. Probabilistic exploration of the trial endpoints may enable greater understanding of the trial findings. We aimed to perform a reanalysis using a Bayesian framework.

Methods
We performed a secondary analysis of all 2927 patients randomized in multi-national STARRT-AKI trial, performed at 168 centers in 15 countries. The primary endpoint, 90-day all-cause mortality, was evaluated using hierarchical Bayesian logistic regression. A spectrum of priors includes optimistic, neutral, and pessimistic priors, along with priors informed from earlier clinical trials. Secondary endpoints (KRT-free days and hospital-free days) were assessed using zero–one inflated beta regression.

Results
The posterior probability of benefit comparing an accelerated versus a standard KRT initiation strategy for the primary endpoint suggested no important difference, regardless of the prior used (absolute difference of 0.13% [95% credible interval [CrI] − 3.30%; 3.40%], − 0.39% [95% CrI − 3.46%; 3.00%], and 0.64% [95% CrI − 2.53%; 3.88%] for neutral, optimistic, and pessimistic priors, respectively). There was a very low probability that the effect size was equal or larger than a consensus-defined minimal clinically important difference. Patients allocated to the accelerated strategy had a lower number of KRT-free days (median absolute difference of − 3.55 days [95% CrI − 6.38; − 0.48]), with a probability that the accelerated strategy was associated with more KRT-free days of 0.008. Hospital-free days were similar between strategies, with the accelerated strategy having a median absolute difference of 0.48 more hospital-free days (95% CrI − 1.87; 2.72) compared with the standard strategy and the probability that the accelerated strategy had more hospital-free days was 0.66.

Conclusions
In a Bayesian reanalysis of the STARRT-AKI trial, we found very low probability that an accelerated strategy has clinically important benefits compared with the standard strategy. Patients receiving the accelerated strategy probably have fewer days alive and KRT-free. These findings do not support the adoption of an accelerated strategy of KRT initiation.