Liver CirrhosisPhase 3SCOTCH;NCT02602210
Supplemental Corticosteroids in Cirrhotic Hypotensive Patients With Suspicion of Sepsis
A Phase 3 study testing Hydrocortisone and NaCL 0.9% in people with Liver Cirrhosis, run by Universitaire Ziekenhuizen KU Leuven at 10 sites in 7 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Liver Cirrhosis
- What is being tested?
- Hydrocortisone and NaCL 0.9%
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 10 sitesin 7 countries
- Study dates
- Jan 2015to 31 Dec 2020
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 21Show fewer
- 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 locations and contacts
10 sites in 7 countries.
10 sites in 7 countries
Spain3 sites
Hospital Clinic Barcelona
Barcelona
Hospital General Universitario Gregorio Maranon
Madrid
Hospital Universitario Ramón y Cajal
Madrid
United Kingdom2 sites
King's College Hospital
London
Derriford Hospital
Plymouth
About this study
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.
Read the 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.
- Conditions
- Liver Cirrhosis
- Being tested
- Hydrocortisone, NaCL 0.9%
- Keywords
- cirrhosis, liver, corticosteroids, hypotension, sepsis, cortisol
- Medical subject headings
- Liver Cirrhosis, Fibrosis, Hypotension, Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HydrocortisoneDrug
Also called solucortef
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.
NaCL 0.9%Drug
Also called sodium chloride
IV bolus of 50 ml NaCL 0.9%; followed by continuous IV infusion of NaCL 0.9%
| Study group | Role | What they receive |
|---|---|---|
| group A | Active comparator | Group A: treated with intravenous hydrocortisone in addition to standard therapy (= treatment group) Receives: Drug: Hydrocortisone |
| group B | Placebo comparator | Group B: IV treatment with NaCL 0.9% in addition to standard therapy (= placebo group) Receives: Drug: NaCL 0.9% |
What is being measured
The primary outcome is the main question the study is designed to answer.
Patient survival at 28 days analysed from the day of randomisation
survival status
Measured: 28days
Secondary outcomes (17)
patient survival at 90 days analysed from the day of randomization
survival status
Measured: 90 days
ICU and hospital mortality
mortality
Measured: from the date of randomisation until ICU discharge or hospital mortality, whichever came first, up to day 90
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 > 24 hours)
Measured: up to day 90
reversal of organ failures
measured with SOFA-score and CLIF (Chronic Liver Failure Consortium)-SOFA score
Measured: up to 90 days
vasopressor doses
administration of vasopressor
Measured: up to 90 days
vasopressor-free days
days without vasopression
Measured: up to 90 days
mechanical ventilation-free days
days without mechanical ventilation
Measured: up to 90 days
need for and duration of renal replacement therapy
days of renal replacement therapy
Measured: up to 90 days
ICU and hospital length-of-stay
days of ICU stay , days of hospital stay
Measured: up to 90 days
acquirement of new infections
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)
Measured: up to 90 days
shock relapse
defined as hypotension recurrence during the tapering period or within 3 days of total discontinuation of study drug
Measured: during tapering period until 3 days after end 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 nasogastric aspirate will not be considered active GI bleeding.
Measured: up to 90 days
glycemic control
measured as units of insulin required to attain glycemic levels between 80 - 140 mg/dl
Measured: during ICU stay, up to 10 days
episode of hyper- (> 180 mg/dl) or hypoglycemia (< 60 mg/dl)
number of episodes of hypo- hyperglycemia
Measured: during study treatment period, up to 10 days
new shock episode
hypotension recurrence with need for vasopressor therapy after 3 days of total discontinuation of study drug
Measured: during study treatment period, up to 13 days
impact of coagulopathy
assessed by disseminated intravascular coagulopathy (DIC)-score
Measured: during ICU stay up to 10 days
incidence of ICU-acquired weakness
occurrence of IC acquired weakness
Measured: during ICU stay, up to 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Nov 2015 (estimated)
- Study startJan 2015
- Primary completion31 Dec 2020
- Study completion31 Dec 2020
Why it stopped: low inclusion rate
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Liver CirrhosisStudies of the same condition, open and under way.
- More trials run by Universitaire Ziekenhuizen KU LeuvenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universitaire Ziekenhuizen KU Leuven
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Philippe Meersseman, MD, Principal investigator, Universitaire Ziekenhuizen KU LeuvenAlexander Wilmer, MD, PhD, Principal investigator, Universitaire Ziekenhuizen KU LeuvenJavier Fernandez, MD,PhD, Principal investigator, Hosp Clinic, Barcelona, Spain
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02602210
- Sponsor's protocol ID
- SCOTCH-SCotCHIS in the UK
- Acronym
- SCOTCH;
- Status last verified
- Jan 2021
- First submitted
- 22 Sep 2015
- Last updated
- 22 Jan 2021
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 40757786
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Supplemental Corticosteroids in Cirrhotic Hypotensive Patients With Suspicion of Sepsis
- ClinicalTrials.gov ID
- NCT02602210
- Acronym / sponsor ID
- SCOTCH; / SCOTCH-SCotCHIS in the UK
- Conditions
- Liver Cirrhosis
- Keywords
- cirrhosis, liver, corticosteroids, hypotension, sepsis, cortisol
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: low inclusion rate
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Universitaire Ziekenhuizen KU LeuvenUniversity, hospital or other
- Study start
- Jan 2015
- Primary completion
- 31 Dec 2020 (actual)
- Study completion
- 31 Dec 2020 (actual)
- First posted
- 11 Nov 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| group A | Active comparator | Drug: HydrocortisoneGroup A: treated with intravenous hydrocortisone in addition to standard therapy (= treatment group) |
| group B | Placebo comparator | Drug: NaCL 0.9%Group B: IV treatment with NaCL 0.9% in addition to standard therapy (= placebo group) |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- All patients with known or recently diagnosed cirrhosis who
- 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.
Key exclusion criteria (21 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HydrocortisoneAlso: solucortefIV 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. | Drug | group A |
| NaCL 0.9%Also: sodium chlorideIV bolus of 50 ml NaCL 0.9%; followed by continuous IV infusion of NaCL 0.9% | Drug | group B |
Primary outcome
Patient survival at 28 days analysed from the day of randomisation
Time frame: 28days
survival status
17 secondary outcomes
patient survival at 90 days analysed from the day of randomization
Time frame: 90 days
ICU and hospital mortality
Time frame: from the date of randomisation until ICU discharge or hospital mortality, whichever came first, up to day 90
reversal of shock
Time frame: up to day 90
reversal of organ failures
Time frame: up to 90 days
vasopressor doses
Time frame: up to 90 days
vasopressor-free days
Time frame: up to 90 days
mechanical ventilation-free days
Time frame: up to 90 days
need for and duration of renal replacement therapy
Time frame: up to 90 days
ICU and hospital length-of-stay
Time frame: up to 90 days
acquirement of new infections
Time frame: up to 90 days
shock relapse
Time frame: during tapering period until 3 days after end of study drug
clinically important bleeding
Time frame: up to 90 days
glycemic control
Time frame: during ICU stay, up to 10 days
episode of hyper- (> 180 mg/dl) or hypoglycemia (< 60 mg/dl)
Time frame: during study treatment period, up to 10 days
new shock episode
Time frame: during study treatment period, up to 13 days
impact of coagulopathy
Time frame: during ICU stay up to 10 days
incidence of ICU-acquired weakness
Time frame: during ICU stay, up to 90 days
Results and safety
The study was stopped early (reason given: low inclusion rate). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2021.
- Derived from this study: PubMed 40757786Meersseman 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.
Related trials for Liver Cirrhosis
RecruitingObservational study
Effectiveness and Clinical Outcomes of Long-term Bulevirtide Monotherapy in Patients With HDV-related Compensated Cirrhosis
Hepatitis D
Recruiting
Optimal Treatment Strategy for Spontaneous Bacterial Peritonitis
Spontaneous Bacterial Peritonitis, Paracentesis
RecruitingObservational study
The Value of Spleen Thickness and Spleen Diameter for Gastroesophageal Varices Diagnosis in Compensated Cirrhosis
Liver Cirrhosis, Gastroesophageal Varices
Recruiting
CirrhosisRx CDS System
Cirrhosis, Decision Support Systems, Clinical
RecruitingPhase 3
Trial to Evaluate ALN-CIDEB in Adults With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
Metabolic Dysfunction-Associated Steatotic Liver Disease, MASLD
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Philippe Meersseman, MD principal investigator
Universitaire Ziekenhuizen KU Leuven
Alexander Wilmer, MD, PhD principal investigator
Universitaire Ziekenhuizen KU Leuven
Javier Fernandez, MD,PhD principal investigator
Hosp Clinic, Barcelona, Spain
10 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Hydrocortisone and NaCL 0.9% in people with Liver Cirrhosis, run by Universitaire Ziekenhuizen KU Leuven at 10 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 22 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Spain, United Kingdom, Belgium, Czechia, Denmark and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: low inclusion rate). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Patient survival at 28 days analysed from the day of randomisation (time frame: 28days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02602210, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2021.