SepsisRECORDSNCT04280497
Rapid Recognition of Corticosteroid Resistant or Sensitive Sepsis
A study testing Administration procedures in people with Sepsis, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sepsis
- What is being tested?
- Administration procedures
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,800 participants
- Where
- 1 siteFrance
- Study dates
- 10 Apr 2020to Dec 2025
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient ≥18 years old;
- Admitted to ICU with proven or suspected infection as the main diagnosis;
- 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;
- Patients who have been tested for one or more RECORDS specific biomarkers:
- CIRCI
- Endocan
Show all 21Show fewer
- GILZ
- DUSP-1
- MDW
- lymphopenia
- Transcriptomic SRS2
- Endotype B
- PCR COVID-19
- PCR Influenza
- PCR other respiratory virus
- Cutaneous vasoconstrictor response to glucocorticoids
- 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;
- Patient affiliated to a social security system or to an universal health coverage (Couverture Maladie Universelle (CMU) in France;
- Patient under guardianship or curatorship will be included;
- Patient in case of simple emergency (legal definition) will be included;
- Patients managed with covid 19 and having biological samples available.
Who cannot join
- Pregnancy;
- Expected death or withdrawal of life-sustaining treatments within 48 hours;
- Previously enrolled in this study
- Formal indication for corticosteroids according to most recent international guidelines
- Vaccination with live virus within past 6 months
- Hypersensitivity to hydrocortisone or fludrocortisone or (microsined betamethasone dipropionate*) or any of their excipients (spc)
- Women of childbearing potential not using contraception
- Nursing women * For patients included in this stratum, if applicable, do not apply the cream to an infected or ulcerated area
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
Department of medical and surgical Intensive Care Unit, Raymond Poincaré Hospital - APHP
Garches, Hauts-de-Seine, 92380
About this study
Official title: A Multicentre Concealed-Allocation Multi-arms Blinded Randomized Controlled Trial to Identify the Best Sepsis Population for Corticotherapy
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).
Read the 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
- Being tested
- Administration procedures
- Keywords
- Sepsis, Corticosteroid, intensive care unit, CS-resistant Sepsis, CS-sensitive Sepsis
- Medical subject headings
- Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Administration proceduresDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Biomarker CIRCI neg: Corticosteroid arm | Experimental | Hydrocortisone plus fludrocortisone as treatment: hydrocortisone hemisuccinate and 9 alpha fludrocortisone as experimental treatment. Receives: Drug: Administration procedures |
| Biomarker CIRCI neg: Placebo arm | Placebo comparator | Placebo: hydrocortisone placebo and 9 alpha fludrocortisone placebo as placebo treatment. Receives: Drug: Administration procedures |
| Biomarker endocan: Corticosteroid arm | Experimental | Hydrocortisone plus fludrocortisone as treatment: hydrocortisone hemisuccinate and 9 alpha fludrocortisone as experimental treatment. Receives: Drug: Administration procedures |
| Biomarker endocan: Placebo arm | Placebo comparator | Placebo: hydrocortisone placebo and 9 alpha fludrocortisone placebo as placebo treatment. Receives: Drug: Administration procedures |
| Biomarker GILZ: Corticosteroid arm | Experimental | Hydrocortisone plus fludrocortisone as treatment: hydrocortisone hemisuccinate and 9 alpha fludrocortisone as experimental treatment. Receives: Drug: Administration procedures |
| Biomarker GILZ: Placebo arm | Placebo comparator | Placebo: hydrocortisone placebo and 9 alpha fludrocortisone placebo as placebo treatment. Receives: Drug: Administration procedures |
| Biomarker CPD: Corticosteroid arm | Experimental | Hydrocortisone plus fludrocortisone as treatment: hydrocortisone hemisuccinate and 9 alpha fludrocortisone as experimental treatment. Receives: Drug: Administration procedures |
| Biomarker CPD: Placebo arm | Placebo comparator | Placebo: hydrocortisone placebo and 9 alpha fludrocortisone placebo as placebo treatment. Receives: Drug: Administration procedures |
| Biomarker Transcriptomic SRS: Corticosteroid arm | Experimental | Hydrocortisone plus fludrocortisone as treatment: hydrocortisone hemisuccinate and 9 alpha fludrocortisone as experimental treatment. Receives: Drug: Administration procedures |
| Biomarker Transcriptomic SRS: Placebo arm | Placebo comparator | Placebo: hydrocortisone placebo and 9 alpha fludrocortisone placebo as placebo treatment. Receives: Drug: Administration procedures |
| Biomarker Endotype B: Corticosteroid arm | Experimental | Hydrocortisone plus fludrocortisone as treatment: hydrocortisone hemisuccinate and 9 alpha fludrocortisone as experimental treatment. Receives: Drug: Administration procedures |
| Biomarker Endotype B: Placebo arm | Placebo comparator | Placebo: hydrocortisone placebo and 9 alpha fludrocortisone placebo as placebo treatment. Receives: Drug: Administration procedures |
What is being measured
The primary outcome is the main question the study is designed to answer.
3-month mortality
Patient's vital status.
Measured: Daily up to 3 months
Persistent organ dysfunction
Persistent organ dysfunction (defined as continued dependency on mechanical ventilation, renal replacement therapy, or vasopressors) and with SOFA score ≤6 up to 90 days.
Measured: At baseline, 1 month and 3 months
Secondary outcomes (18)
Mortality at 7, 14, 28 day and 6 months
Patient's vital status.
Measured: at 7, 14, 28 day and 6 months
Vasopressor free days
defined as the number of days with permanent hemodynamic stability in the absence of any vasopressor agent, norepinephrine, phenylephrine, epinephrine, dopamine, vasopressine or its analogs, and soever. When a patient will die on vasopressor therapy, the corresponding vasopressor free day will be 0.
Measured: through study completion, an average of 6 month
Mechanical ventilation free days
defined as the number of days with permanent appropriate oxygenation while the patients is extubated and breathing spontaneously, i.e. no need for non invasive ventilation, high flow oxygen or CPAP. Other uses of non-invasive ventilation (e.g., chronic night-time use for chronic obstructive pulmonary disease) are not counted. When a patient will die on mechanical ventilation or will be discharge home on mechanical ventilation, the corresponding mechanical ventilation free day will be 0.
Measured: through study completion, an average of 6 month
Organ dysfunction free days
Organ function (including renal function) will be assessed by the SOFA score (Vincent 1996). Organ dysfunction will be defined by a SOFA score of > 6 (Annane 2018). Organ dysfunction free days are defined by the number of days with os total SOFA score of 6 or less. When a patient will die on vasopressor therapy, the corresponding vasopressor free day will be 0.
Measured: through study completion, an average of 6 month
HRQoL in 6-month survivors assessed by the EuroQol-5D (EQ-5D)
This questionnaire is a standardised measure of health status developed to provide a simple, generic measure of health for clinical and economic appraisal. It is made up for two components; health state description and evaluation. The health status is measured in terms of five dimensions; mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. In evaluation part, the respondents evaluate their overall health status using the visual analogue scale.
Measured: at 1, 28, 90 day and 6 months
Proportion of patients with a decision to withhold and/or withdraw active treatments
Measured: through study completion, an average of 6 month
ICU and hospital length of stay
Measured: through study completion, an average of 6 month
Rate of re-admission to the ICU during the 180 days after randomization
Measured: through study completion, an average of 6 month
Safety endpoints: proportion of patients affected by any serious adverse events
Serious adverse events associated with corticosteroids, among the following: hospital-acquired infections, hyperglycemia, hypernatremia, neurological disorders (coma, stroke or muscle weakness, as defined below) during the 90 days after randomization.
Measured: up to 90 days
Coma
Coma will be defined as a Glasgow coma score < 8
Measured: up to 90 days
Neurologic sequelae
Neurologic sequelae will be assessed according to the score on the Muscular Disability Rating Scale (MDRS), with a score of 1 indicating no deficit, 2 minor deficit with no functional disability, 3 distal motor deficit, 4 mild-to-moderate proximal motor deficit, and 5 severe proximal motor deficit.
Measured: up to 90 days
Proportion of patients affected by hospital-acquired infections
Proportion of patients affected by hospital-acquired infections (CTINILS. Définition des infections associées aux soins. 2007, (document in french)).
Measured: up to 90 days
Number of episodes of hyperglycemia
Number of episodes of hyperglycemia (blood glucose levels >150mg/dl) during ICU stay (or up to day 90, whichever occurs first)
Measured: daily during ICU stay or up to 90 days
Number of episodes of hypernatremia
Number of episodes of hypernatremia (serum sodium > 145 mmol/L) during ICU stay (or up to day 90, whichever occurs first)
Measured: daily during ICU stay or up to day 90
Glasgow coma scale at ICU and hospital discharge
Glasgow coma scale at ICU and hospital discharge
Measured: at ICU discharge and hospital discharge
Number of patients with an episode of stroke
Number of patients with an episode of stroke (medical diagnosis as registered in the medical file) during ICU stay (or up to day 90, whichever occurs first)
Measured: daily during ICU stay or up to day 90
Gastroduodenal bleeding
Gastroduodenal bleeding requiring transfusion or hemostatic treatment during ICU stay (or up to day 90, whichever occurs first)
Measured: daily during ICU stay or up to day 90
Adult cognitive function score
Neurological cognitive dysfunction defined as by low score on the PROMIS (Adult cognitive function score).
PROMIS (Patient-Reported Outcomes Measurement Information System): for assessment of fatigue, ability to partake in social activities, physical function, emotional distress, depression, anxiety and cognitive function.
Measured: at 1, 28, 90 day and 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2020
- Study start10 Apr 2020
- Primary completionDec 2025 (estimated)
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for SepsisStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,800 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- Institut National de la Santé Et de la Recherche Médicale, France, Versailles Saint-Quentin-en-Yvelines University, Université Paris-Saclay, Paris 12 Val de Marne University, Commissariat A L'energie Atomique, Beckman Coulter, Inc., Lumedix, Elice, Biothelis
- Responsible party
- Sponsor
- Investigators
- Djillali ANNANE, MD, PhD, Principal investigator, Department of medical and surgical Intensive Care Unit, - Raymond Poincaré Hospital - APHP
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04280497
- Sponsor's protocol ID
- APHP191110
- Other IDs
- 2020-000296-21
- Acronym
- RECORDS
- Status last verified
- Sep 2025
- First submitted
- 17 Feb 2020
- Last updated
- 1 Oct 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 28940011Lamontagne 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.
PubMed 30097460Rochwerg 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.
PubMed 29979221Nishida 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.
PubMed 29445505Rhodes 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.
PubMed 28101605Tavare 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.
PubMed 28360070van 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.
PubMed 28436424Wong 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.
PubMed 25489881Antcliffe 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.
PubMed 30365341Annane 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.
PubMed 28940017Singer 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.
PubMed 26903338ARDS 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.
PubMed 22797452Fleuriet 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.
PubMed 36898751
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicentre Concealed-Allocation Multi-arms Blinded Randomized Controlled Trial to Identify the Best Sepsis Population for Corticotherapy
- ClinicalTrials.gov ID
- NCT04280497
- Acronym / sponsor ID
- RECORDS / APHP191110
- Conditions
- Sepsis
- Keywords
- Sepsis, Corticosteroid, intensive care unit, CS-resistant Sepsis, CS-sensitive Sepsis
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 1,800 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- Institut National de la Santé Et de la Recherche Médicale, France, Versailles Saint-Quentin-en-Yvelines University, Université Paris-Saclay, Paris 12 Val de Marne University, Commissariat A L'energie Atomique, Beckman Coulter, Inc., Lumedix, Elice, Biothelis
- Study start
- 10 Apr 2020 (actual)
- Primary completion
- Dec 2025 (estimated)
- Study completion
- Dec 2025 (estimated)
- First posted
- 21 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 12
| Arm | Type | Receives |
|---|---|---|
| Biomarker CIRCI neg: Corticosteroid arm | Experimental | Drug: Administration proceduresHydrocortisone plus fludrocortisone as treatment: hydrocortisone hemisuccinate and 9 alpha fludrocortisone as experimental treatment. |
| Biomarker CIRCI neg: Placebo arm | Placebo comparator | Drug: Administration proceduresPlacebo: hydrocortisone placebo and 9 alpha fludrocortisone placebo as placebo treatment. |
| Biomarker endocan: Corticosteroid arm | Experimental | Drug: Administration proceduresHydrocortisone plus fludrocortisone as treatment: hydrocortisone hemisuccinate and 9 alpha fludrocortisone as experimental treatment. |
| Biomarker endocan: Placebo arm | Placebo comparator | Drug: Administration proceduresPlacebo: hydrocortisone placebo and 9 alpha fludrocortisone placebo as placebo treatment. |
| Biomarker GILZ: Corticosteroid arm | Experimental | Drug: Administration proceduresHydrocortisone plus fludrocortisone as treatment: hydrocortisone hemisuccinate and 9 alpha fludrocortisone as experimental treatment. |
| Biomarker GILZ: Placebo arm | Placebo comparator | Drug: Administration proceduresPlacebo: hydrocortisone placebo and 9 alpha fludrocortisone placebo as placebo treatment. |
| Biomarker CPD: Corticosteroid arm | Experimental | Drug: Administration proceduresHydrocortisone plus fludrocortisone as treatment: hydrocortisone hemisuccinate and 9 alpha fludrocortisone as experimental treatment. |
| Biomarker CPD: Placebo arm | Placebo comparator | Drug: Administration proceduresPlacebo: hydrocortisone placebo and 9 alpha fludrocortisone placebo as placebo treatment. |
| Biomarker Transcriptomic SRS: Corticosteroid arm | Experimental | Drug: Administration proceduresHydrocortisone plus fludrocortisone as treatment: hydrocortisone hemisuccinate and 9 alpha fludrocortisone as experimental treatment. |
| Biomarker Transcriptomic SRS: Placebo arm | Placebo comparator | Drug: Administration proceduresPlacebo: hydrocortisone placebo and 9 alpha fludrocortisone placebo as placebo treatment. |
| Biomarker Endotype B: Corticosteroid arm | Experimental | Drug: Administration proceduresHydrocortisone plus fludrocortisone as treatment: hydrocortisone hemisuccinate and 9 alpha fludrocortisone as experimental treatment. |
| Biomarker Endotype B: Placebo arm | Placebo comparator | Drug: Administration proceduresPlacebo: hydrocortisone placebo and 9 alpha fludrocortisone placebo as placebo treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Patient ≥18 years old;
- Admitted to ICU with proven or suspected infection as the main diagnosis;
- 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;
- Patients who have been tested for one or more RECORDS specific biomarkers:
- 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;
Key exclusion criteria (8 listed)
- Pregnancy;
- Expected death or withdrawal of life-sustaining treatments within 48 hours;
- Previously enrolled in this study
- Formal indication for corticosteroids according to most recent international guidelines
- Vaccination with live virus within past 6 months
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Administration proceduresHydrocortisone 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. | Drug | Biomarker CIRCI neg: Corticosteroid arm, Biomarker CIRCI neg: Placebo arm, Biomarker CPD: Corticosteroid arm, Biomarker CPD: Placebo arm, Biomarker Endotype B: Corticosteroid arm, Biomarker Endotype B: Placebo arm, Biomarker GILZ: Corticosteroid arm, Biomarker GILZ: Placebo arm, Biomarker Transcriptomic SRS: Corticosteroid arm, Biomarker Transcriptomic SRS: Placebo arm, Biomarker endocan: Corticosteroid arm, Biomarker endocan: Placebo arm |
Primary outcome
3-month mortality
Time frame: Daily up to 3 months
Patient's vital status.
Persistent organ dysfunction
Time frame: At baseline, 1 month and 3 months
Persistent organ dysfunction (defined as continued dependency on mechanical ventilation, renal replacement therapy, or vasopressors) and with SOFA score ≤6 up to 90 days.
18 secondary outcomes
Mortality at 7, 14, 28 day and 6 months
Time frame: at 7, 14, 28 day and 6 months
Vasopressor free days
Time frame: through study completion, an average of 6 month
Mechanical ventilation free days
Time frame: through study completion, an average of 6 month
Organ dysfunction free days
Time frame: through study completion, an average of 6 month
HRQoL in 6-month survivors assessed by the EuroQol-5D (EQ-5D)
Time frame: at 1, 28, 90 day and 6 months
Proportion of patients with a decision to withhold and/or withdraw active treatments
Time frame: through study completion, an average of 6 month
ICU and hospital length of stay
Time frame: through study completion, an average of 6 month
Rate of re-admission to the ICU during the 180 days after randomization
Time frame: through study completion, an average of 6 month
Safety endpoints: proportion of patients affected by any serious adverse events
Time frame: up to 90 days
Coma
Time frame: up to 90 days
Neurologic sequelae
Time frame: up to 90 days
Proportion of patients affected by hospital-acquired infections
Time frame: up to 90 days
Number of episodes of hyperglycemia
Time frame: daily during ICU stay or up to 90 days
Number of episodes of hypernatremia
Time frame: daily during ICU stay or up to day 90
Glasgow coma scale at ICU and hospital discharge
Time frame: at ICU discharge and hospital discharge
Number of patients with an episode of stroke
Time frame: daily during ICU stay or up to day 90
Gastroduodenal bleeding
Time frame: daily during ICU stay or up to day 90
Adult cognitive function score
Time frame: at 1, 28, 90 day and 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2025.
- Background: PubMed 28940011Annane 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: PubMed 30097460Lamontagne 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: PubMed 29979221Rochwerg 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: PubMed 29445505Nishida 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: PubMed 28101605Rhodes 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: PubMed 28360070Tavare 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: PubMed 28436424van 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: PubMed 25489881Wong 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: PubMed 30365341Antcliffe 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: PubMed 28940017Annane 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: PubMed 26903338Singer 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: PubMed 22797452ARDS 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Djillali ANNANE, MD, PhD principal investigator
Department of medical and surgical Intensive Care Unit, - Raymond Poincaré Hospital - APHP
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Administration procedures in people with Sepsis, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 1 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Djillali ANNANE, MD, PhD (+33 1 47 10 77 87, djillali.annane@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
3-month mortality (time frame: Daily up to 3 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04280497, which also lists 13 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2025.