Supplemental Corticosteroids in Cirrhotic Hypotensive Patients With Suspicion of Sepsis (SCOTCH;)

Universitaire Ziekenhuizen KU Leuven

Status and phase: Terminated; Phase 3

Conditions: Liver Cirrhosis

Treatments: Drug: Hydrocortisone; Drug: NaCL 0.9%

Study type: Interventional

Funder types: Other

Identifiers

NCT02602210

SCOTCH-SCotCHIS in the UK

Details and patient eligibility

About

The main goal of the study is to investigate the clinical relevance, efficacy and safety of treating hypotensive cirrhotic patients with suspicion of sepsis and on vasopressors with low-dose hydrocortisone in order to reverse hemodynamic instability and organ failure and to decrease mortality.

Full description

Ample evidence suggests that a significant number of patients (52-77%) with chronic liver disease develop adrenal insufficiency in case of concomitant sepsis. This condition impairs hemodynamic integrity and probably worsens often encountered multiorgan failure. Different groups suggested that treating those patients with corticosteroids gives a faster reversal of hemodynamic instability and even lowers mortality compared to historical controls. However, most of the published data are retrospective and comprise small groups of patients. These data raise the possibility that corticosteroids at stress doses may be beneficial in hypotensive cirrhotics admitted to the ICU but as yet this has not been subjected to a large-scale multicentre randomized controlled clinical trial.

The study will be a double-blind, randomized, placebo-controlled, multicenter trial, involving tertiary intensive care units with expertise in management of patients with decompensated cirrhosis. Patients who satisfy inclusion criteria and do not present any of the exclusion criteria at ICU admission will be randomized into two groups:

• Group A: treated with intravenous hydrocortisone in addition to standard therapy (= treatment group)
• Group B: placebo (NaCl 0.9%) treatment in addition to standard treatment (= placebo group)

If, after adequate fluid resuscitation, patients are still on norepinephrine at a dose of at least 0,1 mcg/kg/min for at least 4 hours, the patient can be randomized. Study drug can be started immediately after randomization but no later than 24 h after initiation of norepinephrine. Patients will receive an intravenous bolus of 50 ml of normal saline (placebo) or an intravenous bolus of 50 ml of normal saline containing 100 mg of hydrocortisone (double-blind) that will be followed by a continuous intravenous infusion of the study drug (hydrocortisone) or placebo. Treatment with study drug (hydrocortisone or placebo) at initial rate will be maintained until the start of day 4 and gradually discontinued (reduction of infusion rate with 0.5 ml/h/d) when 1) patients do not require vasoactive drugs anymore to maintain MAP(mean arterial pressure) > 60 mmHg or > 65 mmHg if associated with signs of hypoperfusion in spite of ongoing adequate fluid resuscitation or 2) in any case after a 7-day treatment period.

Investigators, treating physicians, nurses and patients will be blinded to the intervention.

Enrollment: 100 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• All patients with known or recently diagnosed cirrhosis who

  1. are admitted to the ICU because of persistent hypotension or
  2. develop persistent hypotension while admitted to the ICU,

secondary to proven or suspected infection, in both cases despite adequate fluid resuscitation and with persistent need for low-dose norepinephrine to maintain a mean arterial blood pressure > 60 mmHg or > 65 mmHg if accompanied by signs of hypoperfusion, are eligible for study entry. The diagnosis of cirrhosis is preferably made by histology or based on imaging and laboratory findings.

Exclusion criteria

• Age < 18 or ≥ 80 years
• Patients receiving any vasopressor medication for more than 24 h prior to administration of study drug. Terlipressin initiated for treatment of hepatorenal syndrome or variceal bleeding is allowed
• Patients with known hypoadrenalism
• Active GI bleeding (unless controlled for >72 hours) or hemorrhagic shock.
• Cardiogenic shock or severe cardiac dysfunction (CI <2 l/min/ m2)
• Active uncontrolled hepatitis B infection
• HIV infection
• Evidence of current malignancy (except hepatocellular carcinoma within transplant criteria or non-melanocytic skin cancer)
• Therapy with any corticosteroid (oral or intravenous) in the last 3 months
• Patients who received etomidate within the past 3 days
• Severe acute alcoholic hepatitis (biopsy proven)
• Chronic hemodialysis
• Severe chronic heart disease (NYHA class III or IV)
• Severe chronic obstructive pulmonary disease (GOLD III or IV)
• Severe psychiatric disorder
• Child-Pugh score C14 -15
• SOFA score > 16 points at inclusion
• Pregnant or breastfeeding women
• Contraindications for systemic steroids
• Refusal to consent
• Patients who cannot provide prior informed consent and when there is documented evidence that the patient has no legal surrogate decision maker and it appears unlikely that the patient will regain consciousness or sufficient ability to provide delayed informed consent

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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100 participants in 2 patient groups, including a placebo group

group A

Active Comparator group

Description:

Group A: treated with intravenous hydrocortisone in addition to standard therapy (= treatment group)

Treatment:

Drug: Hydrocortisone

group B

Placebo Comparator group

Description:

Group B: IV treatment with NaCL 0.9% in addition to standard therapy (= placebo group)

Treatment:

Drug: NaCL 0.9%