Rapid Recognition of Corticosteroid Resistant or Sensitive Sepsis

NCT ID: NCT04280497

Last Updated: 2025-10-01

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 1800 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-04-10
• Study Completion Date: 2025-12-31

Brief 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).

Detailed Description

The potential benefits of a lower dose ( ≤ 400 mg of hydrocortisone or equivalent per day), and a longer duration at full dose ( ≥ three days) of treatment, have been investigated in numerous randomized controlled trials over the past three decades. In the past two years, guidelines for clinical practices about corticosteroids use in sepsis have been released. All but one of the guidelines, recommended against the use of corticosteroids in sepsis, except in patients with septic shock and poorly responsive to fluid replacement and vasopressor therapy. Some guidelines suggested that corticosteroids should be given as a continuous infusion rather than intermittent boluses.

Corticosteroids survival benefit is not affected by age, gender, disease severity, type of infection, source of infection, or type of pathogens. There is currently no diagnostic test for CS sensitivity/resistance in sepsis. The scientific community is competing to identify markers delineating between patients who draw survival benefit from corticosteroids (CS-sensitive sepsis) and those who may be harmed (CS-resistant sepsis). In sepsis, the deregulated response may result in systemic inflammation and organs damage, or immune paresis and secondary infections. Obviously, patients with systemic inflammation may benefit from CS whereas those with immune paresis may deteriorate. The study team had have looked for an interaction between survival in response to corticosteroids and the presence of CIRCI according to the ACTH test results (cortisol increment of less than 9µg/dL). The benefits from corticosteroids were more important in patients with CIRCI in the Ger-Inf-05 trial but not in the APROCCHS trial. Thus, current sepsis guidelines suggest that the ACTH test may not reliably guide the use of corticosteroids. Indeed, this test provides information neither on corticosteroids bioactivity nor on patient's immune status, when this information should precede any corticotherapy. Recent studies suggested that a transcriptomic signature based on 100 genes may identify a subset of paediatric sepsis that had increased risk of death when exposed to corticosteroids. Another study found transcriptomic based sepsis response signatures (SRS) associated with immune paresis (SRS1) or with systemic inflammation (SRS 2). In this study, patients with a SRS 2 transcriptomic signature had significantly higher mortality when treated with hydrocortisone. Thus, we have started exploring the mechanisms of sensitivity/resistance to corticosteroids in sepsis, namely by investigating endocan, as a surrogate of patient's inflammatory status, and GILZ expression as a marker of corticosteroids bioactivity.

This is a new multicentre concealed-allocation multi-arms, parallel-group, adaptive blinded randomized controlled trial. The overall objective of the trial is to determine whether different signatures of immune status and/or corticosteroids biological activity influence the responses to hydrocortisone plus fludrocortisone of adults with sepsis. To remain pragmatic, this trial has broad eligibility criteria and includes all patients admitted to the ICU with a primary diagnosis of sepsis. Patients will be randomly assigned to hydrocortisone plus fludrocortisone or placebo for 7 days, targeting 1800 patients with full follow-up up to 6 months.

Conditions

Sepsis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Biomarker CIRCI neg: Corticosteroid arm

Hydrocortisone plus fludrocortisone as treatment: hydrocortisone hemisuccinate and 9 alpha fludrocortisone as experimental treatment.

Group Type: EXPERIMENTAL

Administration procedures

Intervention Type: DRUG

Hydrocortisone hemisuccinate / hydrocortisone placebo will be given as 50 mg intravenous bolus every 6 hours;

9 alpha fludrocortisone / 9 alpha fludrocortisone placebo will be given as a 50 μg tablet via a nasogastric tube once per day in the morning.

Study drugs will be started immediately after randomization (day 0 of the study), until discharge from ICU for a maximal duration of 7 days. Study drugs will be stopped without tapering off.

Biomarker CIRCI neg: Placebo arm

Placebo: hydrocortisone placebo and 9 alpha fludrocortisone placebo as placebo treatment.

Group Type: PLACEBO_COMPARATOR

Administration procedures

Intervention Type: DRUG

Hydrocortisone hemisuccinate / hydrocortisone placebo will be given as 50 mg intravenous bolus every 6 hours;

9 alpha fludrocortisone / 9 alpha fludrocortisone placebo will be given as a 50 μg tablet via a nasogastric tube once per day in the morning.

Study drugs will be started immediately after randomization (day 0 of the study), until discharge from ICU for a maximal duration of 7 days. Study drugs will be stopped without tapering off.

Biomarker endocan: Corticosteroid arm

Hydrocortisone plus fludrocortisone as treatment: hydrocortisone hemisuccinate and 9 alpha fludrocortisone as experimental treatment.

Group Type: EXPERIMENTAL

Administration procedures

Intervention Type: DRUG

Hydrocortisone hemisuccinate / hydrocortisone placebo will be given as 50 mg intravenous bolus every 6 hours;

9 alpha fludrocortisone / 9 alpha fludrocortisone placebo will be given as a 50 μg tablet via a nasogastric tube once per day in the morning.

Study drugs will be started immediately after randomization (day 0 of the study), until discharge from ICU for a maximal duration of 7 days. Study drugs will be stopped without tapering off.

Biomarker endocan: Placebo arm

Placebo: hydrocortisone placebo and 9 alpha fludrocortisone placebo as placebo treatment.

Group Type: PLACEBO_COMPARATOR

Administration procedures

Intervention Type: DRUG

Hydrocortisone hemisuccinate / hydrocortisone placebo will be given as 50 mg intravenous bolus every 6 hours;

9 alpha fludrocortisone / 9 alpha fludrocortisone placebo will be given as a 50 μg tablet via a nasogastric tube once per day in the morning.

Study drugs will be started immediately after randomization (day 0 of the study), until discharge from ICU for a maximal duration of 7 days. Study drugs will be stopped without tapering off.

Biomarker GILZ: Corticosteroid arm

Hydrocortisone plus fludrocortisone as treatment: hydrocortisone hemisuccinate and 9 alpha fludrocortisone as experimental treatment.

Group Type: EXPERIMENTAL

Administration procedures

Intervention Type: DRUG

Hydrocortisone hemisuccinate / hydrocortisone placebo will be given as 50 mg intravenous bolus every 6 hours;

9 alpha fludrocortisone / 9 alpha fludrocortisone placebo will be given as a 50 μg tablet via a nasogastric tube once per day in the morning.

Study drugs will be started immediately after randomization (day 0 of the study), until discharge from ICU for a maximal duration of 7 days. Study drugs will be stopped without tapering off.

Biomarker GILZ: Placebo arm

Placebo: hydrocortisone placebo and 9 alpha fludrocortisone placebo as placebo treatment.

Group Type: PLACEBO_COMPARATOR

Administration procedures

Intervention Type: DRUG

Hydrocortisone hemisuccinate / hydrocortisone placebo will be given as 50 mg intravenous bolus every 6 hours;

9 alpha fludrocortisone / 9 alpha fludrocortisone placebo will be given as a 50 μg tablet via a nasogastric tube once per day in the morning.

Study drugs will be started immediately after randomization (day 0 of the study), until discharge from ICU for a maximal duration of 7 days. Study drugs will be stopped without tapering off.

Biomarker CPD: Corticosteroid arm

Hydrocortisone plus fludrocortisone as treatment: hydrocortisone hemisuccinate and 9 alpha fludrocortisone as experimental treatment.

Group Type: EXPERIMENTAL

Administration procedures

Intervention Type: DRUG

Hydrocortisone hemisuccinate / hydrocortisone placebo will be given as 50 mg intravenous bolus every 6 hours;

9 alpha fludrocortisone / 9 alpha fludrocortisone placebo will be given as a 50 μg tablet via a nasogastric tube once per day in the morning.

Study drugs will be started immediately after randomization (day 0 of the study), until discharge from ICU for a maximal duration of 7 days. Study drugs will be stopped without tapering off.

Biomarker CPD: Placebo arm

Placebo: hydrocortisone placebo and 9 alpha fludrocortisone placebo as placebo treatment.

Group Type: PLACEBO_COMPARATOR

Administration procedures

Intervention Type: DRUG

Hydrocortisone hemisuccinate / hydrocortisone placebo will be given as 50 mg intravenous bolus every 6 hours;

9 alpha fludrocortisone / 9 alpha fludrocortisone placebo will be given as a 50 μg tablet via a nasogastric tube once per day in the morning.

Study drugs will be started immediately after randomization (day 0 of the study), until discharge from ICU for a maximal duration of 7 days. Study drugs will be stopped without tapering off.

Biomarker Transcriptomic SRS: Corticosteroid arm

Hydrocortisone plus fludrocortisone as treatment: hydrocortisone hemisuccinate and 9 alpha fludrocortisone as experimental treatment.

Group Type: EXPERIMENTAL

Administration procedures

Intervention Type: DRUG

Hydrocortisone hemisuccinate / hydrocortisone placebo will be given as 50 mg intravenous bolus every 6 hours;

9 alpha fludrocortisone / 9 alpha fludrocortisone placebo will be given as a 50 μg tablet via a nasogastric tube once per day in the morning.

Study drugs will be started immediately after randomization (day 0 of the study), until discharge from ICU for a maximal duration of 7 days. Study drugs will be stopped without tapering off.

Biomarker Transcriptomic SRS: Placebo arm

Placebo: hydrocortisone placebo and 9 alpha fludrocortisone placebo as placebo treatment.

Group Type: PLACEBO_COMPARATOR

Administration procedures

Intervention Type: DRUG

Hydrocortisone hemisuccinate / hydrocortisone placebo will be given as 50 mg intravenous bolus every 6 hours;

9 alpha fludrocortisone / 9 alpha fludrocortisone placebo will be given as a 50 μg tablet via a nasogastric tube once per day in the morning.

Study drugs will be started immediately after randomization (day 0 of the study), until discharge from ICU for a maximal duration of 7 days. Study drugs will be stopped without tapering off.

Biomarker Endotype B: Corticosteroid arm

Hydrocortisone plus fludrocortisone as treatment: hydrocortisone hemisuccinate and 9 alpha fludrocortisone as experimental treatment.

Group Type: EXPERIMENTAL

Administration procedures

Intervention Type: DRUG

Hydrocortisone hemisuccinate / hydrocortisone placebo will be given as 50 mg intravenous bolus every 6 hours;

9 alpha fludrocortisone / 9 alpha fludrocortisone placebo will be given as a 50 μg tablet via a nasogastric tube once per day in the morning.

Study drugs will be started immediately after randomization (day 0 of the study), until discharge from ICU for a maximal duration of 7 days. Study drugs will be stopped without tapering off.

Biomarker Endotype B: Placebo arm

Placebo: hydrocortisone placebo and 9 alpha fludrocortisone placebo as placebo treatment.

Group Type: PLACEBO_COMPARATOR

Administration procedures

Intervention Type: DRUG

Hydrocortisone hemisuccinate / hydrocortisone placebo will be given as 50 mg intravenous bolus every 6 hours;

9 alpha fludrocortisone / 9 alpha fludrocortisone placebo will be given as a 50 μg tablet via a nasogastric tube once per day in the morning.

Study drugs will be started immediately after randomization (day 0 of the study), until discharge from ICU for a maximal duration of 7 days. Study drugs will be stopped without tapering off.

Interventions

Administration procedures

Hydrocortisone hemisuccinate / hydrocortisone placebo will be given as 50 mg intravenous bolus every 6 hours;

9 alpha fludrocortisone / 9 alpha fludrocortisone placebo will be given as a 50 μg tablet via a nasogastric tube once per day in the morning.

Study drugs will be started immediately after randomization (day 0 of the study), until discharge from ICU for a maximal duration of 7 days. Study drugs will be stopped without tapering off.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Patient ≥18 years old;

2. Admitted to ICU with proven or suspected infection as the main diagnosis;

3. Community acquired pneumonia related sepsis or vasopressors dependency (norepinephrine, epinephrine, vasopressin, dopamine, phenylephrine) or septic shock (vasopressor to maintain mean blood pressure of at least 65 mmHg and lactate levels above 2 mmol/l) or acute respiratory distress syndrome (ARDS: a- acute onset, i.e. within one week of an apparent clinical insult and with progression of respiratory syndrome, b- bilateral opacities on chest imaging not explained by other pulmonary pathologies, e.g. pleural effusion, atelectasis, nodules etc, c- no evidence for heart failure or volume overload, d- PaO2/FiO2 ≤ 300 mm Hg, - PEEP ≥ 5 cm H2O;

4. Patients who have been tested for one or more RECORDS specific biomarkers:

1. CIRCI

2. Endocan

3. GILZ

4. DUSP-1

5. MDW

6. lymphopenia

7. Transcriptomic SRS2

8. Endotype B

9. PCR COVID-19

10. PCR Influenza

11. PCR other respiratory virus

12. Cutaneous vasoconstrictor response to glucocorticoids

5. Patient who has signed an informed and written consent whevener he/she is able of consent, if not, if not ascent from his/her representant whenever he/she is present at time of screening for inclusion;

6. Patient affiliated to a social security system or to an universal health coverage (Couverture Maladie Universelle (CMU) in France;

7. Patient under guardianship or curatorship will be included;

8. Patient in case of simple emergency (legal definition) will be included;

9. Patients managed with covid 19 and having biological samples available.

Exclusion Criteria

1. Pregnancy;

2. Expected death or withdrawal of life-sustaining treatments within 48 hours;

3. Previously enrolled in this study

4. Formal indication for corticosteroids according to most recent international guidelines

5. Vaccination with live virus within past 6 months

6. Hypersensitivity to hydrocortisone or fludrocortisone or (microsined betamethasone dipropionate*) or any of their excipients (spc)

7. Women of childbearing potential not using contraception

8. Nursing women * For patients included in this stratum, if applicable, do not apply the cream to an infected or ulcerated area

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institut National de la Santé Et de la Recherche Médicale, France

OTHER_GOV

Sponsor Role: collaborator

Versailles Saint-Quentin-en-Yvelines University

OTHER

Sponsor Role: collaborator

Université Paris-Saclay

OTHER

Sponsor Role: collaborator

Paris 12 Val de Marne University

OTHER

Sponsor Role: collaborator

Commissariat A L'energie Atomique

OTHER_GOV

Sponsor Role: collaborator

Beckman Coulter, Inc.

INDUSTRY

Sponsor Role: collaborator

Lumedix

UNKNOWN

Sponsor Role: collaborator

Elice

UNKNOWN

Sponsor Role: collaborator

Biothelis

UNKNOWN

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Djillali ANNANE, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Department of medical and surgical Intensive Care Unit, - Raymond Poincaré Hospital - APHP

Locations

Department of medical and surgical Intensive Care Unit, Raymond Poincaré Hospital - APHP

Garches, Hauts-de-Seine, France

Site Status: RECRUITING

Countries

France

Central Contacts

Djillali ANNANE, MD, PhD

Role: CONTACT

djillali.annane@aphp.fr

+33 1 47 10 77 87

References

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.

Reference Type: BACKGROUND

PMID: 28940011 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 30097460 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 29979221 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 29445505 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 28101605 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 28360070 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 28436424 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25489881 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 30365341 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 28940017 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 26903338 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 22797452 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 36898751 (View on PubMed)

Other Identifiers

2020-000296-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

APHP191110

Identifier Type: -

Identifier Source: org_study_id