Cirrhotic patients under vasopressors admitted to the ICU because of persisting hypotension and with suspected infection.
Conditions
Interventions
Trade Name: Hydrocortison VUAB 100 mg, powder for solution for injection
Pharmaceutical Form: Concentrate and solvent for solution for injection/infusion
INN or Proposed INN: solu-cortef
Other descrip
Sponsors
University Hospitals Leuven
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: All patients with known or recently diagnosed cirrhosis who a) are admitted to the ICU because of persistent hypotension or b) develop persistent hypotension while admitted to the ICU, in both cases despite adequate fluid resuscitation and with need for low-dose norepinephrine, are eligible for study entry. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 280 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 76
Exclusion criteria
Exclusion criteria: •Age 72 hours) or hemorrhagic shock. •Cardiogenic shock or severe cardiac dysfunction (CI 12 points at inclusion •Pregnant or breastfeeding women •Contraindications for systemic steroids •Refusal to consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine whether low doses of hydrocortisone improves the 28-day mortality when added to the standard management of cirrhotic patients with vasopressor dependent shock.;Secondary Objective: •Determine whether therapy with hydrocortisone: -improve ICU, hospital and 90-day mortality -shorten time to resolution of shock and reversal of organ failure -shorten ICU and hospital LOS -reduce new organ failure -is associated with shock relapse -is associated with development of new infection episodes or development of infections -is associated with development of adverse events related to gastrointestinal bleeding -is associated with severe hyperglycemia -is associated with the development of critical illness polyneuropathy •Estimate the incidence of adrenal failure according to the proposed definition. •Identify and characterize those who benefit most from corticosteroid •Evaluate diagnostic and prognostic value of the Synacthentest in the selection of patients for treatment with steroids. •Establish diagnostic criteria and propose a definition for cirrhosis related corticosteroid insufficiency •Elucidate pathophysiology of adrenal insufficiency in cirrhotics ;Primary end point(s): Patient survival at 28 days analysed from the day of randomisation (28-day mortality);Timepoint(s) of evaluation of this end point: Day 28 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •patient survival at 90 days analysed from the day of randomization •ICU and hospital mortality •reversal of shock: time in days from start of placebo or active medication to resolution of shock as defined as cessation of continuous vasopressor medication (for > 4 hours) •reversal of organ failures: measured with SOFA-score and CLIF-SOFA score •vasopressor doses •vasopressor-free days •mechanical ventilation-free days •renal replacement-free days •ICU and hospital length-of-stay •acquirement of new infections (bacterial and/or fungal): defined according to CDC criteria (pneumonia, bacteremia, spontaneous bacterial peritonitis, catheter-related bloodstream infections, skin infections and others) •shock relapse defined as hypotension recurrence during the tapering period or within 3 days of total discontinuation of study drug •clinically important bleeding defined as new melena, new haematemesis or unexplained fall in haemoglobin > 2g/dl (not related to volume expansion). The presence of ‘coffee ground’ aspirate from NG aspirate will not be considered active GI bleeding. •glycemic control: measured as units of insulin required to attain glycemic levels between 100 – 140 mg/dl •episode of hyper- (> 180 mg/dl) or hypoglycemia (< 60 mg/dl) ;Timepoint(s) of evaluation of this end point: day 90 | — |
Countries
Czech Republic
Contacts
Public ContactSecretary general internal medicine
University Hospitals Leuven
Outcome results
None listed