Echocardiography-guided Cirrhosis and Liver Failure-Intensive Care Protocol Sepsis

NCT07286643 | Recruiting DMC

• 1 other identifier: PGI/IEC/02/2024-3008
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 1

Brief Summary

• Point-of-care echocardiography is used to guide septic shock resuscitation in patients with severe sepsis in the intensive care unit (ICU), but without systematic evidence for efficacy in critically patients with Cirrhosis and Severe Sepsis.
• Due to portal hypertension, these patients have a hyperdynamic circulation, increased capillary permeability, splanchnic arteriolar vasodilation, reduced effective circulating blood volume and may have latent cirrhotic cardiomyopathy (CCM).
• Hence assessment of volume status and cardiac reserve using conventional central venous pressure (CVP) or mean arterial pressure (MAP) remains difficult. Novelty:
• In two recent trials, the role of 5% albumin vs PlasmalyteTM (FRISC study)(1) and 20% albumin vs. PlasmalyteTM (ALPS study) (2) were reported as the primary resuscitation fluid. Neither trial showed a clear long term survival benefit of albumin over balanced salt solution (BSS). In fact, the ALPS trial reported that there was increased risk of pulmonary edema with use of 20% albumin as fluid resuscitation.
• A major limitation of such trial data is that the focus is on choice of fluid rather than looking at hemodynamic goals of resuscitation, resulting in protocolized overzealous fluid administration.
• This may result in albumin-related pulmonary edema, and precipitation of overt heart failure in patients with silent CCM.
• POC-Echo-based fluid resuscitation can prevent pulmonary edema and consequently respiratory failure, while ensuring renal and tissue perfusion.
• It is unclear if choice of fluid or appropriate targets of resuscitation drive the survival benefit in the intensive care management of cirrhosis with severe sepsis. Objectives:
• The investigators will conduct an ICU based randomised controlled feasibility trial comparing two measures of resuscitation: Echocardiography (ECHO) Guided septic shock resuscitation vs. a modified Goal-Directed Fluid Therapy (GDT) as recommended by sepsis guidelines which use protocol fluids.
• The study will validate the role of POC-Echo parameters as volume assessment tools (cardiac index, systemic vascular resistance index) to determine endpoints of fluid resuscitation and need for vasopressors.
• Lastly, the study aims to determine the presence of CCM in this population, and its impact on clinical outcomes. Methods POC-ECHO will be done within 1 hours of admission to the liver ICU and at 24h, 48 h and 72 hours in patients with cirrhosis with systolic blood pressure of \<90 mmHg or a mean arterial pressure \<65 mmHg. Resuscitation target is maintenance of MAP ≥65 mmHg with use of fluids and/or vasopressors. Clinical, cardiac biomarkers, and survival data based on resuscitation fluids will be prospectively collected. CCM will be defined as per CCM Consortium (2020) criteria. Expected outcome. The key questions to be answered in the resuscitation of critically ill patients with cirrhosis and sepsis induced hypotension are:
• What should be best method of ensuring adequate fluid resuscitation i.e. fluid resuscitation protocol?
• Which measurable clinical parameter can be used to determine adequacy of fluid resuscitation, and as a predictor of mortality outcomes at 7 and 28 days?
• Whether early fluid resuscitation translates into better clinical outcome in decreasing duration of hospital and intensive care unit (ICU) stay, prevention of AKI and prevention of secondary sepsis?

Conditions

Cirrhosis, Liver; Cirrhotic Cardiomyopathy; Septic Shock

Keywords

echocardiography; cardiac output monitoring; hemodynamics; fluid resuscitation.; POCUS

Outcome Measures

Primary Outcomes (1)

• Reduction in volume of resuscitation fluid to attain reversal of shock in POCUS vs Conventional goal-directed therapy at 24 h

  Dose of balanced salt solution (BSS) and 5% albumin in either arm

  Time of randomization to 24 hours

Secondary Outcomes (13)

• Assessment of all-cause mortality

  From time of randomization up to Day 7

• Attainment of MAP> 65mmHg

  from time of randomization up to time point of reversal of shock

• Assessment of all-cause mortality

  From date of randomization until Day 28

• Total dose of vasopressor usage in either arm.

  From date of randomization until 24 hours

• Total dose of vasopressor usage in either arm.

  From date of randomization until Day 7

Study Arms (2)

ECHO arm

EXPERIMENTAL

Other Names: Point of Care- Echo-cardiogram,POCUS Description: • The patients in septic shock with MAP\< 65mmHg, with IVC diameter \<18mm and IVCCI≥40% in spontaneously breathing patients, would be regarded as fluid depleted state and will be given a fluid challenge with 250-500 ml of balanced salt solution. Those who increment cardiac index by 15% will be continued on fluid boluses with BSS and 5% albumin will be started as ongoing resuscitation within 1 h, which is a standard fluid of choice in patients with cirrhosis soon after the bolus BSS is infused. Fluids will be administered as per periodic POCUS with cardiac US targets, IVC, IJV indices, delta Velocity time integral, and maintenance of MAP\>65 mmHg. In the Intervention arm (ECHO) arm, we propose a dynamic Cardiac ultrasound target-based fluid resuscitation strategy.

Diagnostic Test: POCUS

Conventional goal directed therapy. (CGDT)

ACTIVE COMPARATOR

Fixed Target Strategy Fluid boluses would be administered until a central venous pressure (CVP) of 8-10 mmHg is achieved. Till the central line is placed, the shock index (heart rate/ systolic blood pressure) will be used instead of the CVP and IVC indices. Thus fluids (500 ml balanced salt solution followed by 5% albumin) will be administered for a shock index ≥1 and till CVP is placed. • When CVP goal is achieved vasopressors will be started to target MAP ≥ 65mmHg. Once MAP target is achieved, ScVO2 ≥70% and lactate clearance \>10% will be targeted. • If ScVO2 is \<70% and lactate clearance is \<10%, noradrenaline will be started and titrated upwards. take it up to a maximum dose. • Second choice of pressor agent will be vasopressin. • Thus. CGDT group targets CVP, MAP, followed by ScVO2 ≥70% and lactate clearance .

Diagnostic Test: Fixed Resuscitation Strategy based on Target MAP

Interventions

POCUS DIAGNOSTIC_TEST

* In the Intervention arm (ECHO) arm, we propose a Cardiac ultrasound target-based fluid resuscitation. This incorporates the fluid assessment based on POCUS and myocardial dysfunction based on cardiac ultrasound (cardiac index, myocardial contractility, stroke volume) and portal hypertension-related systemic vasodilation accentuated by sepsis (systemic vascular resistance index or SVRI). * The POCUS -velocity time integral and stroke volume index will be used to determine fluid responsiveness. * If there is an increment in cardiac index by 15% after giving a fluid bolus (i.e. 250-500 ml of BSS in 15min), we can define 'fluid responsiveness' present. * The achievement of lactate clearance, MAP target \>65mmHg and ScV02 \>70% remains similar as the fixed target strategy. The main resuscitation fluid remains 5% albumin in this arm. Albumin infusion will be titrated based on lung ultrasound.

ECHO arm

Fixed Resuscitation Strategy based on Target MAP DIAGNOSTIC_TEST

• Fluid boluses would be administered until a CVP of 8-10 mmHg is achieved and IVC diameter is between 1.8-2 cm with 20-30% collapsibility. Till the central line is placed, the shock index (heart rate/ systolic blood pressure) will be used instead of the CVP. Thus fluids (500 ml crystalloid followed by 5% albumin) will be administered for a shock index ≥1 and till CVP is placed. * When CVP goal is achieved vasopressors will be started to target MAP ≥ 65mmHg. Once MAP target is achieved, ScVO2 ≥70% and lactate clearance \>10% will be targeted. * If ScVO2 is \<70% and lactate clearance is \<10%, noradrenaline will be started and titrated upwards. take it up to a maximum dose. * Second choice of pressor agent will be vasopressin. * Thus. CGDT group targets CVP, MAP\>65 mmHg, followed by ScVO2 ≥70% and lactate clearance in a step wise way.

Conventional goal directed therapy. (CGDT)

Eligibility Criteria

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

You may qualify if:

• Critically ill patient with cirrhosis of any etiology
• Sepsis-related Hypotension (MAP \<65mmHg or SBP \<90mmHg)
• yrs of age -

You may not qualify if:

• Already on vasopressors/inotropes
• Severe pre-existing cardiopulmonary disease like porto-pulmonary hypertension (PPH), known coronary artery disease, congenital or valvular heart disease, prosthetic cardiac valves, dilated or restrictive cardiomyopathy.
• Poor chest wall window due to left pleural effusion, left pneumothorax, small intercostal spaces that restrict performance of a POCUS.
• Active bleeding like variceal bleed
• Cerebrovascular events
• Chronic renal disease - End Stage Renal Disease (ESRD)/ patient on renal replacement therapy
• Admission to ICU following liver transplantation, burns, cardiac surgery
• Previous transjugular intra hepatic portosystemic shunt (TIPS),
• Hepatocellular carcinoma
• Pregnant or lactating women
• Informed consent refused by patient or attendants
• Active COVID-19 infection

Sponsors & Collaborators

• Post Graduate Institute of Medical Education and Research, Chandigarh: lead

Study Sites (1)

PGIMER Chandigarh

Chandigarh, 160012, India

RECRUITING

MeSH Terms

Conditions

Liver Cirrhosis; Shock, Septic

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Sepsis; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Shock

Central Study Contacts

Dr Madhumita Premkumar, DM

CONTACT

7087003409; drmadhumitap@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: POC ECHO and CGDT Arm
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Additional Professor

Model Details: Randomized Controlled Trial

Study Record Dates

• First Submitted: May 22, 2024
• First Posted: December 16, 2025
• Study Start: January 1, 2026
• Primary Completion (Estimated): August 30, 2028
• Study Completion (Estimated): December 30, 2028
• Last Updated: December 16, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)