HYDROCORTISONE for Cardiac arrest|Post-resuscitation shock

Inclusion criteria

• {"criterion_text":"- Adult patients (≥18y)\n- Cardiac arrest (in-hospital or out-of-hospital) with sustained ROSC (> 30 minutes) admitted to the ICU\n- Post-resuscitation shock defined as arterial hypotension (SAP < 90 mmHg or MAP < 65 mmHg) unresponsive to adequate fluid loading, which occurred within the first 24 hours after ROSC and requiring norepinephrine tartrate/epinephrine continuous infusion at a dose greater or equal to 0.2μg/kg/min for at least 3 hours\n- A maximal delay between the start of norepinephrine infusion and randomization of 9 hours;\n- Informed written consent of a legally authorized close relative, or emergency procedure"}

Exclusion criteria

• {"criterion_text":"- Evidence for a traumatic or a neurological cause of cardiac arrest\n- inclusion in another randomized trial involving a drug that could interact with either interventional drug\n- Hypersensitivity to argipressin and to its excipients\n- Hypersensitivity to hydrocortisone and to its excipients\n- Legal protection (i.e. incompetence to provide consent, guardianship, curator or incarceration)\n- No affiliation with the French health care system\n- In-ICU cardiac arrest\n- Shock due to uncontrolled haemorrhage\n- Previously known adrenal insufficiency\n- Limitation of life-sustaining therapies\n- Ongoing treatment by any steroids, at a daily dose greater or equal to 7.5mg/d equivalent prednisone for at least 3 weeks\n- Ongoing extra-corporeal circulatory assistance\n- Gastrointestinal bleeding in the past 6 weeks\n- Pregnant or breastfeeding women"}

Primary endpoints

• {"endpoint_text":"- the good neurological outcome at day-30. This will be evaluated using the Glasgow Outcome Scale (GOS, addendum 18.5.1) dichotomized as follow: good neurological outcome for categories 4 and 5 and poor neurological outcome or death for categories 3, 2 and 1. The GOS will be obtained at day-30 from an in-hospital visit if the patient is still hospitalized or from telephone contact with patients, relatives or general practitioners.","definition_or_measurement_approach":"Evaluated using the Glasgow Outcome Scale (GOS) dichotomized: good neurological outcome = GOS categories 4 and 5; poor neurological outcome or death = GOS categories 3, 2, 1. GOS obtained at day-30 from in-hospital visit if hospitalized or by telephone contact with patient, relatives or general practitioners."}

Secondary endpoints

• {"endpoint_text":"- Vital status at day-30 Time to day-30 caused by irreversible cardiovascular failure defined as death in pharmacologically uncontrollable hypotension (mean arterial blood pressure <60 mmHg) despite maximal ICU care, or withdrawal of care based on same, as previously defined (Witten L, Resuscitation 2019)","definition_or_measurement_approach":"Death in pharmacologically uncontrollable hypotension (mean arterial blood pressure <60 mmHg) despite maximal ICU care, or withdrawal of care based on same (definition referenced to Witten L, Resuscitation 2019)."}
• {"endpoint_text":"- Time to day-30 caused by neurological withdrawal of care. Withdrawal of care will be based on expectations of a poor neurological recovery based on most recent guidelines (Sandroni C, ICM 2015).","definition_or_measurement_approach":"Withdrawal of care based on expectation of poor neurological recovery according to guidelines (Sandroni C, ICM 2015)."}
• {"endpoint_text":"- Time to day-30 by comorbid withdrawal of care. Comorbid withdrawal of care or refusal of lifesustaining therapy based on the expectation of a poor quality of life. This may be related to a preexisting or newly discovered terminal illness or other serious medical condition (e.g. dementia or cancer).","definition_or_measurement_approach":"Withdrawal/refusal of life-sustaining therapy due to expectation of poor future quality of life related to preexisting or newly discovered terminal/serious condition (e.g., dementia, cancer)."}
• {"endpoint_text":"- Time to brain death (according to French legislation)","definition_or_measurement_approach":"Brain death determined according to French legislation criteria."}
• {"endpoint_text":"- Time to recurrent cardiac arrest-Proportion of patients dead from a cause not listed above","definition_or_measurement_approach":"Time to recurrent cardiac arrest; includes proportion of deaths from causes not listed in other categories."}
• {"endpoint_text":"- Glasgow outcome score –extended at day-30. This score will be evaluated similarly to the primary endpoint","definition_or_measurement_approach":"Glasgow Outcome Scale - Extended at day-30, evaluated similarly to primary endpoint dichotomisation."}
• {"endpoint_text":"- Neuron-specific enolase (NSE) blood level measured 48 and 72 hours after CA","definition_or_measurement_approach":"Serum neuron-specific enolase measured at 48 and 72 hours after cardiac arrest."}
• {"endpoint_text":"- Number of days between inclusion and day-30 without :catecholamines - norepinephrine - AVP - inotropic support","definition_or_measurement_approach":"Count of days between inclusion and day-30 free from catecholamines (norepinephrine), AVP, and inotropic support."}
• {"endpoint_text":"- Number of patients alive and free of norepinephrine at day-3, -5 and -7 Number of patients alive and free of AVP at day-3, - 5 and -7","definition_or_measurement_approach":"Proportion/count of patients alive and not receiving norepinephrine or AVP at days 3, 5 and 7."}
• {"endpoint_text":"- Proportion of patients with new onset of atrial fibrillation at day-30","definition_or_measurement_approach":"Proportion of patients with new onset atrial fibrillation occurring between inclusion and day-30."}
• {"endpoint_text":"- Left ventricular ejection fraction at day-1, 2, 3 and 7. Left ventricular ejection fraction will be evaluated using echocardiography (either trans-thoracic or trans-esophageal)","definition_or_measurement_approach":"Left ventricular ejection fraction measured by echocardiography (transthoracic or transesophageal) at days 1, 2, 3 and 7."}
• {"endpoint_text":"- Number of mechanical ventilation free days at day- 30","definition_or_measurement_approach":"Number of days free from mechanical ventilation up to day-30."}
• {"endpoint_text":"- Number of renal replacement therapy free days at day-30","definition_or_measurement_approach":"Number of days free from renal replacement therapy up to day-30."}
• {"endpoint_text":"- KDIGO classification at day-7 and day-30. The day- 30 KDIGO classification will be estimated on the creatinine criteria as theurine criteria will be unlikely available. The estimated glomerular filtration rate will becalculated using the MDRD equation.","definition_or_measurement_approach":"Acute kidney injury classification per KDIGO at day-7 and day-30; day-30 KDIGO estimated using creatinine criteria only; estimated GFR calculated using MDRD equation."}
• {"endpoint_text":"- Proportion of patients with acute coronary syndrome defined according to the international guidelines (2015 ESC guidelines) as to know: the detection of an increase and/or a decrease of cardiac troponin and at least one of the following: (1) symptoms of ischemia, (2) new or presumed new significant ST-T wave changes or left bundle branch block on 12-lead ECG; (3) development of pathological Q waves on ECG, (4) imaging evidence of new or presumed new loss of viable myocardium or regional wall mot","definition_or_measurement_approach":"Acute coronary syndrome defined per 2015 ESC guidelines: troponin rise/fall plus at least one of symptoms of ischemia, new significant ECG changes or LBBB, new pathological Q waves, or imaging evidence of new loss of viable myocardium/regional wall motion abnormality."}
• {"endpoint_text":"- Proportion of patients with mesenteric ischemia at day-30, diagnosed on clinical assessment and a computed tomography angiography or endoscopy","definition_or_measurement_approach":"Mesenteric ischemia diagnosed by clinical assessment and confirmed by CT angiography or endoscopy at day-30."}
• {"endpoint_text":"- Proportion of patients with clinically diagnosed digital ischemia at day-30","definition_or_measurement_approach":"Clinically diagnosed digital ischemia assessed by clinical evaluation at day-30."}
• {"endpoint_text":"- Proportion of patients with central diabetes insipidus at argipressin (AVP) weaning. Central diabetes insipidus is defined by a polyuria (> 50mL/kg/24h) associated with an increased plasmatic osmolality (> 300mOsm/L) and a decreased urinary osmolality (< 300mOsm/L)","definition_or_measurement_approach":"Central diabetes insipidus defined as polyuria (>50 mL/kg/24h) with plasma osmolality >300 mOsm/L and urine osmolality <300 mOsm/L at AVP weaning."}
• {"endpoint_text":"- Proportion of patients with gastro-intestinal bleeding at day-30. Gastrointestinal bleeding will be diagnosed as a clinical gastrointestinal bleeding simultaneously with a drop of blood hemoglobin level","definition_or_measurement_approach":"Gastrointestinal bleeding diagnosed clinically with concurrent drop in hemoglobin level by day-30."}
• {"endpoint_text":"- Proportion of patients with hyperglycemia occurrence, defined as the number of episodes of blood glucose level higher than 11mmol/L between inclusion and day- 7","definition_or_measurement_approach":"Hyperglycemia episodes defined as blood glucose >11 mmol/L between inclusion and day-7; proportion of patients with ≥1 episodes."}
• {"endpoint_text":"- ICU and hospital lengths of stay (in days)","definition_or_measurement_approach":"Length of stay in ICU and in hospital measured in days."}

France

Earliest CTIS Part Ii Submission Date

07-10-2024

Latest Decision Or Authorization Date

04-04-2025

Processing Time Days

179

Number Of Sites

17

Number Of Participants

380

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France