Rapid Recognition of Corticosteroid Resistant or Sensitive Sepsis

Summary

Main objective and primary endpoint: To compare the effect hydrocortisone plus fludrocortisone vs. placebo on a composite of death or persistent organ dysfunction - defined as continued dependency on mechanical ventilation, new renal replacement therapy, or vasopressors - assessed at 90 days on intensive care unit (ICU) adults and having different biological profiles for immune responses and corticosteroids bioactivity. Secondary objectives and endpoints: * Mortality and health-related quality of life at 6 months; * Daily organ function (SOFA score days 1, 2, 3, 4, 7, 10, 14, 28, and 90); * Daily secondary infections (up to 90 days) * Daily blood and urinary levels of glucose, sodium and potassium (up to 28 day) * Daily gastroduodenal bleeding (up to 28 day) * Daily cognitive function and muscles' strength (days 1 to 28, 90 and 180 days).

Timeline

Start

2020-04-10

Primary completion

2025-12

Completion

2025-12

Publications

• Background Annane D, Pastores SM, Rochwerg B, Arlt W, Balk RA, Beishuizen A, Briegel J, Carcillo J, Christ-Crain M, Cooper MS, Marik PE, Umberto Meduri G, Olsen KM, Rodgers S, Russell JA, Van den Berghe G. Guidelines for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in critically ill patients (Part I): Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM) 2017. Intensive Care Med. 2017 Dec;43(12):1751-1763. doi: 10.1007/s00134-017-4919-5. Epub 2017 Sep 21.
• Background Lamontagne F, Rochwerg B, Lytvyn L, Guyatt GH, Moller MH, Annane D, Kho ME, Adhikari NKJ, Machado F, Vandvik PO, Dodek P, Leboeuf R, Briel M, Hashmi M, Camsooksai J, Shankar-Hari M, Baraki MK, Fugate K, Chua S, Marti C, Cohen D, Botton E, Agoritsas T, Siemieniuk RAC. Corticosteroid therapy for sepsis: a clinical practice guideline. BMJ. 2018 Aug 10;362:k3284. doi: 10.1136/bmj.k3284. No abstract available.
• Background Rochwerg B, Oczkowski SJ, Siemieniuk RAC, Agoritsas T, Belley-Cote E, D'Aragon F, Duan E, English S, Gossack-Keenan K, Alghuroba M, Szczeklik W, Menon K, Alhazzani W, Sevransky J, Vandvik PO, Annane D, Guyatt G. Corticosteroids in Sepsis: An Updated Systematic Review and Meta-Analysis. Crit Care Med. 2018 Sep;46(9):1411-1420. doi: 10.1097/CCM.0000000000003262.
• Background Nishida O, Ogura H, Egi M, Fujishima S, Hayashi Y, Iba T, Imaizumi H, Inoue S, Kakihana Y, Kotani J, Kushimoto S, Masuda Y, Matsuda N, Matsushima A, Nakada TA, Nakagawa S, Nunomiya S, Sadahiro T, Shime N, Yatabe T, Hara Y, Hayashida K, Kondo Y, Sumi Y, Yasuda H, Aoyama K, Azuhata T, Doi K, Doi M, Fujimura N, Fuke R, Fukuda T, Goto K, Hasegawa R, Hashimoto S, Hatakeyama J, Hayakawa M, Hifumi T, Higashibeppu N, Hirai K, Hirose T, Ide K, Kaizuka Y, Kan'o T, Kawasaki T, Kuroda H, Matsuda A, Matsumoto S, Nagae M, Onodera M, Ohnuma T, Oshima K, Saito N, Sakamoto S, Sakuraya M, Sasano M, Sato N, Sawamura A, Shimizu K, Shirai K, Takei T, Takeuchi M, Takimoto K, Taniguchi T, Tatsumi H, Tsuruta R, Yama N, Yamakawa K, Yamashita C, Yamashita K, Yoshida T, Tanaka H, Oda S. The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016). Acute Med Surg. 2018 Feb 5;5(1):3-89. doi: 10.1002/ams2.322. eCollection 2018 Jan.
• Background Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, Kumar A, Sevransky JE, Sprung CL, Nunnally ME, Rochwerg B, Rubenfeld GD, Angus DC, Annane D, Beale RJ, Bellinghan GJ, Bernard GR, Chiche JD, Coopersmith C, De Backer DP, French CJ, Fujishima S, Gerlach H, Hidalgo JL, Hollenberg SM, Jones AE, Karnad DR, Kleinpell RM, Koh Y, Lisboa TC, Machado FR, Marini JJ, Marshall JC, Mazuski JE, McIntyre LA, McLean AS, Mehta S, Moreno RP, Myburgh J, Navalesi P, Nishida O, Osborn TM, Perner A, Plunkett CM, Ranieri M, Schorr CA, Seckel MA, Seymour CW, Shieh L, Shukri KA, Simpson SQ, Singer M, Thompson BT, Townsend SR, Van der Poll T, Vincent JL, Wiersinga WJ, Zimmerman JL, Dellinger RP. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-377. doi: 10.1007/s00134-017-4683-6. Epub 2017 Jan 18.
• Background Tavare A, O'Flynn N. Recognition, diagnosis, and early management of sepsis: NICE guideline. Br J Gen Pract. 2017 Apr;67(657):185-186. doi: 10.3399/bjgp17X690401. No abstract available.
• Background van der Poll T, van de Veerdonk FL, Scicluna BP, Netea MG. The immunopathology of sepsis and potential therapeutic targets. Nat Rev Immunol. 2017 Jul;17(7):407-420. doi: 10.1038/nri.2017.36. Epub 2017 Apr 24.
• Background Wong HR, Cvijanovich NZ, Anas N, Allen GL, Thomas NJ, Bigham MT, Weiss SL, Fitzgerald J, Checchia PA, Meyer K, Shanley TP, Quasney M, Hall M, Gedeit R, Freishtat RJ, Nowak J, Shekhar RS, Gertz S, Dawson E, Howard K, Harmon K, Beckman E, Frank E, Lindsell CJ. Developing a clinically feasible personalized medicine approach to pediatric septic shock. Am J Respir Crit Care Med. 2015 Feb 1;191(3):309-15. doi: 10.1164/rccm.201410-1864OC.
• Background Antcliffe DB, Burnham KL, Al-Beidh F, Santhakumaran S, Brett SJ, Hinds CJ, Ashby D, Knight JC, Gordon AC. Transcriptomic Signatures in Sepsis and a Differential Response to Steroids. From the VANISH Randomized Trial. Am J Respir Crit Care Med. 2019 Apr 15;199(8):980-986. doi: 10.1164/rccm.201807-1419OC.
• Background Annane D, Pastores SM, Arlt W, Balk RA, Beishuizen A, Briegel J, Carcillo J, Christ-Crain M, Cooper MS, Marik PE, Meduri GU, Olsen KM, Rochwerg B, Rodgers SC, Russell JA, Van den Berghe G. Critical illness-related corticosteroid insufficiency (CIRCI): a narrative review from a Multispecialty Task Force of the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM). Intensive Care Med. 2017 Dec;43(12):1781-1792. doi: 10.1007/s00134-017-4914-x. Epub 2017 Sep 21.
• Background Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287.
• Background ARDS Definition Task Force; Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L, Slutsky AS. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012 Jun 20;307(23):2526-33. doi: 10.1001/jama.2012.5669.
• Fleuriet J, Heming N, Meziani F, Reignier J, Declerq PL, Mercier E, Muller G, Colin G, Monnet X, Robine A, Siami S, Uhel F, Quenot JP, Plantefeve G, Badie J, Schneider F, Cerf C, Troche G, Monchi M, Mira JP, Francois B, Chevret S, Annane D; RECORDS consortium; CRICS TRIGGERSEP network. Rapid rEcognition of COrticosteRoiD resistant or sensitive Sepsis (RECORDS): study protocol for a multicentre, placebo-controlled, biomarker-guided, adaptive Bayesian design basket trial. BMJ Open. 2023 Mar 10;13(3):e066496. doi: 10.1136/bmjopen-2022-066496.

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Indications