Supplemental Corticosteroids in Cirrhotic Hypotensive Patients With Suspicion of Sepsis

NCT02602210 | Terminated Phase 3 DMC

• 1 other identifier: SCOTCH-SCotCHIS in the UK
• Study Type: interventional
• Target: 100
• Locations: 7 countries
• Sites: 10

Brief Summary

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.

Conditions

Liver Cirrhosis

Keywords

cirrhosis; liver; corticosteroids; hypotension; sepsis; cortisol

Outcome Measures

Primary Outcomes (1)

• Patient survival at 28 days analysed from the day of randomisation

  survival status

  28days

Secondary Outcomes (17)

• patient survival at 90 days analysed from the day of randomization

  90 days

• ICU and hospital mortality

  from the date of randomisation until ICU discharge or hospital mortality, whichever came first, up to day 90

• reversal of shock

  up to day 90

• reversal of organ failures

  up to 90 days

• vasopressor doses

  up to 90 days

Study Arms (2)

group A

ACTIVE COMPARATOR

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

Drug: Hydrocortisone

group B

PLACEBO COMPARATOR

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

Drug: NaCL 0.9%

Interventions

Hydrocortisone DRUG

IV bolus of 100 mg hydrocortisone in 50ml NaCl 0.9% (sodium chloride); followed by continuous IV infusion of 200 mg hydrocortisone in 50 ml NaCl 0.9% at a rate of 2 ml/h until the start of day 4.Reduction of infusion rate with 0.5 ml/h/day.

Also known as: solucortef

group A

NaCL 0.9% DRUG

IV bolus of 50 ml NaCL 0.9%; followed by continuous IV infusion of NaCL 0.9%

Also known as: sodium chloride

group B

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients with known or recently diagnosed cirrhosis who
• are admitted to the ICU because of persistent hypotension or
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead

Study Sites (10)

Universitaire Ziekenhuizen Leuven

Leuven, Vlaams Brabant, 3000, Belgium

Location

Institute for Clinical and Experimental Medicine

Prague, Czechia

Location

Rigshospitalet, University of Copenhagen

Copenhagen, Denmark

Location

University Medical Center Hamburg-Eppendorf

Hamburg, Germany

Location

San Giovanni Battista Hospital

Turin, Italy

Location

Hospital Clinic Barcelona

Barcelona, Spain

Location

Hospital General Universitario Gregorio Maranon

Madrid, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, Spain

Location

King's College Hospital

London, United Kingdom

Location

Derriford Hospital

Plymouth, United Kingdom

Location

Related Publications (1)

• Meersseman P, Hernandez-Tejero M, Diaz JM, Wauters J, Hermans G, Aziz F, Ceunen H, Prado V, Langouche L, Arteaga M, Acevedo J, Lleixa M, Zapatero J, Toapanta D, Arroyo V, Wilmer A, Fernandez J. Low-Dose Hydrocortisone in Cirrhotic Patients With Septic Shock: A Double-Blind Randomised Placebo-Controlled Trial. Liver Int. 2025 Sep;45(9):e70257. doi: 10.1111/liv.70257.

  PMID: 40757786 DERIVED

MeSH Terms

Conditions

Liver Cirrhosis; Fibrosis; Hypotension; Sepsis

Interventions

Hydrocortisone; Sodium Chloride

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Vascular Diseases; Cardiovascular Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Philippe Meersseman, MD

  Universitaire Ziekenhuizen KU Leuven

  PRINCIPAL INVESTIGATOR

• Alexander Wilmer, MD, PhD

  Universitaire Ziekenhuizen KU Leuven

  PRINCIPAL INVESTIGATOR

• Javier Fernandez, MD,PhD

  Hosp Clinic, Barcelona, Spain

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 22, 2015
• First Posted: November 11, 2015
• Study Start: January 1, 2015
• Primary Completion: December 31, 2020
• Study Completion: December 31, 2020
• Last Updated: January 22, 2021

Record last verified: 2021-01

Locations

ES (3); DE (1); DK (1); BE (1); CZ (1); IT (1); GB (2)