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

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ClinicalTrials.gov Identifier: NCT02602210
Recruitment Status : Unknown
Verified October 2017 by Universitaire Ziekenhuizen Leuven.
Recruitment status was:  Recruiting
First Posted : November 11, 2015
Last Update Posted : October 1, 2018
Sponsor:
Information provided by (Responsible Party):
Universitaire Ziekenhuizen Leuven

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.

Condition or disease Intervention/treatment Phase
Liver Cirrhosis Drug: Hydrocortisone Drug: NaCL 0.9% Phase 3

Detailed 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 356 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Supplemental Corticosteroids in Cirrhotic Hypotensive Patients With Suspicion of Sepsis
Study Start Date : January 2015
Estimated Primary Completion Date : May 2019


Arm Intervention/treatment
Active Comparator: group A
Group A: treated with intravenous hydrocortisone in addition to standard therapy (= treatment group)
Drug: Hydrocortisone
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.
Other Name: solucortef

Placebo Comparator: group B
Group B: IV treatment with NaCL 0.9% in addition to standard therapy (= placebo group)
Drug: NaCL 0.9%
IV bolus of 50 ml NaCL 0.9%; followed by continuous IV infusion of NaCL 0.9%
Other Name: sodium chloride




Primary Outcome Measures :
  1. Patient survival at 28 days analysed from the day of randomisation [ Time Frame: 28days ]
    survival status


Secondary Outcome Measures :
  1. patient survival at 90 days analysed from the day of randomization [ Time Frame: 90 days ]
    survival status

  2. ICU and hospital mortality [ Time Frame: from the date of randomisation until ICU discharge or hospital mortality, whichever came first, up to day 90 ]
    mortality

  3. reversal of shock [ Time Frame: up to day 90 ]
    time in days from start of placebo or active medication to resolution of shock as defined as cessation of continuous vasopressor medication (for > 24 hours)

  4. reversal of organ failures [ Time Frame: up to 90 days ]
    measured with SOFA-score and CLIF (Chronic Liver Failure Consortium)-SOFA score

  5. vasopressor doses [ Time Frame: up to 90 days ]
    administration of vasopressor

  6. vasopressor-free days [ Time Frame: up to 90 days ]
    days without vasopression

  7. mechanical ventilation-free days [ Time Frame: up to 90 days ]
    days without mechanical ventilation

  8. need for and duration of renal replacement therapy [ Time Frame: up to 90 days ]
    days of renal replacement therapy

  9. ICU and hospital length-of-stay [ Time Frame: up to 90 days ]
    days of ICU stay , days of hospital stay

  10. acquirement of new infections [ Time Frame: up to 90 days ]
    bacterial and/or fungal: defined according to CDC (Centers for Diseases Control) criteria (pneumonia, bacteremia, spontaneous bacterial peritonitis, catheter-related bloodstream infections, skin infections and others)

  11. shock relapse [ Time Frame: during tapering period until 3 days after end of study drug ]
    defined as hypotension recurrence during the tapering period or within 3 days of total discontinuation of study drug

  12. clinically important bleeding [ Time Frame: up to 90 days ]
    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 nasogastric aspirate will not be considered active GI bleeding.

  13. glycemic control [ Time Frame: during ICU stay, up to 10 days ]
    measured as units of insulin required to attain glycemic levels between 80 - 140 mg/dl

  14. episode of hyper- (> 180 mg/dl) or hypoglycemia (< 60 mg/dl) [ Time Frame: during study treatment period, up to 10 days ]
    number of episodes of hypo- hyperglycemia

  15. new shock episode [ Time Frame: during study treatment period, up to 13 days ]
    hypotension recurrence with need for vasopressor therapy after 3 days of total discontinuation of study drug

  16. impact of coagulopathy [ Time Frame: during ICU stay up to 10 days ]
    assessed by disseminated intravascular coagulopathy (DIC)-score

  17. incidence of ICU-acquired weakness [ Time Frame: during ICU stay, up to 90 days ]
    occurrence of IC acquired weakness



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02602210


Contacts
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Contact: Philippe Meersseman, MD +32 16341335 philippe.meersseman@uzleuven.be
Contact: Alexander Wilmer, MD, PhD +32 16 344275 alexander.wilmer@uzleuven.be

Locations
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Belgium
Universitaire Ziekenhuizen Leuven Recruiting
Leuven, Vlaams Brabant, Belgium, 3000
Contact: Philippe Meersseman    +3216341335    philippe.meersseman@uzleuven.be   
Contact: Alexander Wilmer       alexander.wilmer@uzleuven.be   
Sub-Investigator: Philippe Meersseman         
Principal Investigator: Alexander Wilmer         
Czechia
Institute for Clinical and Experimental Medicine Recruiting
Prague, Czechia
Contact: Jan Sperl       jan.sperl@ikem.cz   
Principal Investigator: Jan Sperl         
Sub-Investigator: Sona Frankova         
Sub-Investigator: Eva Kieslichova         
Denmark
Rigshospitalet, University of Copenhagen Not yet recruiting
Copenhagen, Denmark
Contact: Fin S Larsen       fin.stolze.larsen@rh.regionh.dk   
Principal Investigator: Fin S Larsen         
Germany
University Medical Center Hamburg-Eppendorf Not yet recruiting
Hamburg, Germany
Contact: Valentin Fuhrmann       v.fuhrmann@uke.de   
Principal Investigator: Valentin Fuhrmann         
Sub-Investigator: Thomas Horvatits         
Sub-Investigator: Daniel Benten         
Italy
San Giovanni Battista Hospital Not yet recruiting
Turin, Italy
Contact: Antonio Ottobrelli       aottobrelli@cittadellasalute.to.it   
Principal Investigator: Antonio Ottobrelli         
Sub-Investigator: Davide Stradella         
Spain
Hospital Clinic Barcelona Recruiting
Barcelona, Spain
Contact: Javier Fernandez       JFDEZ@clinic.ub.es   
Contact: Rita Garcia       RIGARCIA@clinic.ub.es   
Principal Investigator: Javier Fernandez         
Hospital General Universitario Gregorio Maranon Recruiting
Madrid, Spain
Contact: Rafael Banares       rbanares@telefonica.net   
Principal Investigator: Rafael Banares         
Hospital Universitario Ramón y Cajal Recruiting
Madrid, Spain
Contact: Agustin Albillos       agustin.albillos@uah.es   
Principal Investigator: Agustin Albillos         
United Kingdom
King's College Hospital Not yet recruiting
London, United Kingdom
Contact: William Bernal       william.bernal@nhs.net   
Principal Investigator: William Bernal         
Derriford Hospital Recruiting
Plymouth, United Kingdom
Contact: Juan Acevedo, PI       jacevedo@nhs.net   
Contact: Victoria Yates, Nat. Coordin       victoriayates@nhs.net   
Sponsors and Collaborators
Universitaire Ziekenhuizen Leuven
Investigators
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Principal Investigator: Philippe Meersseman, MD Universitaire Ziekenhuizen Leuven
Principal Investigator: Alexander Wilmer, MD, PhD Universitaire Ziekenhuizen Leuven
Principal Investigator: Javier Fernandez, MD,PhD Hosp Clinic, Barcelona, Spain
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Responsible Party: Universitaire Ziekenhuizen Leuven
ClinicalTrials.gov Identifier: NCT02602210    
Other Study ID Numbers: SCOTCH-SCotCHIS in the UK
First Posted: November 11, 2015    Key Record Dates
Last Update Posted: October 1, 2018
Last Verified: October 2017
Keywords provided by Universitaire Ziekenhuizen Leuven:
cirrhosis
liver
corticosteroids
hypotension
sepsis
cortisol
Additional relevant MeSH terms:
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Sepsis
Liver Cirrhosis
Fibrosis
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Liver Diseases
Digestive System Diseases
Hydrocortisone
Hydrocortisone hemisuccinate
Anti-Inflammatory Agents