20% Albumin vs. Balanced Salt Solution as Resuscitation Fluid in Cirrhosis With Sepsis Induced Hypotension

NCT05441878 | Unknown Phase 4 DMC

• 1 other identifier: IEC/11/2019/1496
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with cirrhosis patients have a high incidence of sepsis which can trigger decompensation and may result in prolonged hospital stay and increased mortality. About 30%-50% admissions of patients with cirrhosis have sepsis at presentation and about 15% patients admitted to hospital develop sepsis during the hospital stay . After infection develops, the patient may develop acute kidney injury (AKI), shock, encephalopathy or disseminated intravascular coagulation (DIC) further decreasing the chances of survival. In fact, sepsis in patients with cirrhosis is associated with 15% in-hospital mortality, approximately double that of patients without sepsis. So, sepsis is directly responsible for 30-50% of deaths in cirrhosis . Therefore, it is critical to manage sepsis early and appropriately in cirrhosis to reduce the complications and mortality. Early administration of fluids, source control and empirical antibiotics along with vasopressors if refractory shock are essential components of treatment in all patients with sepsis. Currently, the most accepted strategy for early sepsis management is a combination of early goal directed therapy (EGDT) and physiological parameters, such as urine output, lactate clearance, and administration of antibiotics, within 1 hour of presentation . The use of central venous pressure assessment is fallacious for gauging adequacy of fluid resuscitation in cirrhosis, and the difficulty of performing echocardiographic assessments in the setting of ascites and cirrhotic cardiomyopathy is also well described .

Conditions

Cirrhosis, Liver; Acute-On-Chronic Liver Failure; Shock, Septic; Shock Hypovolemic

Outcome Measures

Primary Outcomes (9)

• To compare the efficacy of 20% Albumin vs Plasmalyte in the first 3 -6 hours of volume resuscitation in cirrhosis with sepsis induced hypotension and assess IVC dynamics.

  To compare the IVC dynamics in patients with cirrhosis and sepsis induced hypotension

  At enrolment

• To compare the efficacy of 20% Albumin vs Plasmalyte in the first 3 -6 hours of volume resuscitation in cirrhosis with sepsis induced hypotension and assess IVC dynamics.

  To compare the IVC dynamics in patients with cirrhosis and sepsis induced hypotension

  At 6 hours

• To compare the efficacy of 20% Albumin vs Plasmalyte in the first 3 -6 hours of volume resuscitation in cirrhosis with sepsis induced hypotension and assess IVC dynamics.

  To compare the IVC dynamics in patients with cirrhosis and sepsis induced hypotension

  At 24 hours

• To compare the efficacy of 20% Albumin vs Plasmalyte in the first 3 -6 hours of volume resuscitation in cirrhosis with sepsis induced hypotension and assess IVC dynamics.

  To compare the IVC dynamics in patients with cirrhosis and sepsis induced hypotension

  At 48 hours.

• To compare the efficacy of 20% Albumin vs Plasmalyte in the first 3 -6 hours of volume resuscitation in cirrhosis with sepsis induced hypotension and assess dynamic changes in cardiac output, stroke volume and E/e' echocardiographic parameters.

  To compare the cardiac output in patients with cirrhosis and sepsis induced hypotension

  At enrolment

• To compare the efficacy of 20% Albumin vs Plasmalyte in the first 3 -6 hours of volume resuscitation in cirrhosis with sepsis induced hypotension and assess dynamic changes in cardiac output, stroke volume and E/e' echocardiographic parameters.

  To compare the cardiac output in patients with cirrhosis and sepsis induced hypotension

  At 24 hours

• To compare the efficacy of 20% Albumin vs Plasmalyte in the first 3 -6 hours of volume resuscitation in cirrhosis with sepsis induced hypotension and assess dynamic changes in cardiac output, stroke volume and E/e' echocardiographic parameters.

  To compare the cardiac output in patients with cirrhosis and sepsis induced hypotension

  At 48 hours.

• To compare the efficacy of 20% Albumin vs Plasmalyte in the first 3 -6 hours of volume resuscitation in cirrhosis with sepsis induced hypotension and assess new onset of hepatorenal syndrome (HRS) or acute kidney injury (AKI)

  To compare the new onset of hepatorenal syndrome (HRS) or acute kidney injury (AKI)in patients with cirrhosis and sepsis induced hypotension

  At enrolment

• To compare the efficacy of 20% Albumin vs Plasmalyte in the first 3 -6 hours of volume resuscitation in cirrhosis with sepsis induced hypotension and assess new onset of hepatorenal syndrome (HRS) or acute kidney injury (AKI)

  To compare the new onset of hepatorenal syndrome (HRS) or acute kidney injury (AKI)in patients with cirrhosis and sepsis induced hypotension

  At 48 hours.

Secondary Outcomes (5)

• Urinary marker of AKI (NGal)

  At enrolment

• Change in urinary markers of AKI (NGal)

  At 24 hours.

• Change in urinary markers of AKI(NGal)

  At 48 hours.

• To compare the efficacy of 20% Albumin vs Plasmalyte in the first 3 -6 hours of volume resuscitation in cirrhosis with sepsis induced hypotension., and assess vasopressor requirement

  At enrolment

• To compare the efficacy of 20% Albumin vs Plasmalyte in the first 3 -6 hours of volume resuscitation in cirrhosis with sepsis induced hypotension., and assess vasopressor requirement

  At 24 hours

Study Arms (2)

20% Albumin arm

EXPERIMENTAL

20% Albumin in a dose of 20-40 gm per day as infusion over 12-24 h

Drug: 20% albumin; Drug: Balanced salt solution

Balanced salt solution arm

ACTIVE COMPARATOR

Fluid resuscitation protocol includes use of an immediate 500 ml bolus of crystalloid i.e., balanced salt solution (BSS) or 0.9% normal saline (Rescue phase), followed by 20 ml/kg fluid in the first 6 hours titrated to target MAP of \> 65mmHg.The second phase of fluid resuscitation (Optimization phase) will be performed as per IVC targets, attainment of lactate clearance, and LUS score to prevent overload.

Drug: Balanced salt solution

Interventions

20% albumin DRUG

Albumin arm for resuscitation fluid

20% Albumin arm

Balanced salt solution DRUG

Only Balanced salt solution will be used.

20% Albumin arm; Balanced salt solution arm

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinical/Imaging or Biopsy proven liver cirrhosis of any etiology who consent for enrolment.
• Hypotension (Mean arterial pressure \<65mmHg or Systolic blood pressure \<90mmHg)
• Aged between18-65 yrs

You may not qualify if:

• Already received colloid or more than 2 litres of fluid without baseline echocardiographic assessment.
• Already on vasopressors/inotropes
• Severe pre-existing cardiopulmonary disease
• Acute Respiratory Distress Syndrome (ARDS)
• 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
• Brain death or likely brain death within 24 hours
• Previous adverse reaction to human albumin solution
• Pregnant or lactating women
• Informed consent refused by patient or attendants

Sponsors & Collaborators

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

Study Sites (1)

Postgraduate Institute of Medical Education and Research

Chandigarh, 160012, India

RECRUITING

Related Publications (7)

• Borzio M, Salerno F, Piantoni L, Cazzaniga M, Angeli P, Bissoli F, Boccia S, Colloredo-Mels G, Corigliano P, Fornaciari G, Marenco G, Pistara R, Salvagnini M, Sangiovanni A. Bacterial infection in patients with advanced cirrhosis: a multicentre prospective study. Dig Liver Dis. 2001 Jan-Feb;33(1):41-8. doi: 10.1016/s1590-8658(01)80134-1.

  PMID: 11303974 BACKGROUND

• Navasa M, Fernandez J, Rodes J. Bacterial infections in liver cirrhosis. Ital J Gastroenterol Hepatol. 1999 Oct;31(7):616-25.

  PMID: 10604106 BACKGROUND

• Wong F, Bernardi M, Balk R, Christman B, Moreau R, Garcia-Tsao G, Patch D, Soriano G, Hoefs J, Navasa M; International Ascites Club. Sepsis in cirrhosis: report on the 7th meeting of the International Ascites Club. Gut. 2005 May;54(5):718-25. doi: 10.1136/gut.2004.038679.

  PMID: 15831923 BACKGROUND

• Moreau R, Hadengue A, Soupison T, Kirstetter P, Mamzer MF, Vanjak D, Vauquelin P, Assous M, Sicot C. Septic shock in patients with cirrhosis: hemodynamic and metabolic characteristics and intensive care unit outcome. Crit Care Med. 1992 Jun;20(6):746-50. doi: 10.1097/00003246-199206000-00008.

  PMID: 1597026 BACKGROUND

• ARISE Investigators; ANZICS Clinical Trials Group; Peake SL, Delaney A, Bailey M, Bellomo R, Cameron PA, Cooper DJ, Higgins AM, Holdgate A, Howe BD, Webb SA, Williams P. Goal-directed resuscitation for patients with early septic shock. N Engl J Med. 2014 Oct 16;371(16):1496-506. doi: 10.1056/NEJMoa1404380. Epub 2014 Oct 1.

  PMID: 25272316 BACKGROUND

• Mouncey PR, Osborn TM, Power GS, Harrison DA, Sadique MZ, Grieve RD, Jahan R, Harvey SE, Bell D, Bion JF, Coats TJ, Singer M, Young JD, Rowan KM; ProMISe Trial Investigators. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med. 2015 Apr 2;372(14):1301-11. doi: 10.1056/NEJMoa1500896. Epub 2015 Mar 17.

  PMID: 25776532 BACKGROUND

• Marik PE, Baram M, Vahid B. Does central venous pressure predict fluid responsiveness? A systematic review of the literature and the tale of seven mares. Chest. 2008 Jul;134(1):172-8. doi: 10.1378/chest.07-2331.

  PMID: 18628220 BACKGROUND

MeSH Terms

Conditions

Liver Cirrhosis; Acute-On-Chronic Liver Failure; Shock, Septic; Shock

Interventions

Albumins; Hanks Balanced Salt Solution

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Proteins; Amino Acids, Peptides, and Proteins

Central Study Contacts

Madhumita Premkumar, DM

CONTACT

01722756344; drmadhumitap@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant professor, Department of Hepatology

Study Record Dates

• First Submitted: April 26, 2022
• First Posted: July 1, 2022
• Study Start: August 15, 2020
• Primary Completion: October 1, 2023
• Study Completion: December 1, 2023
• Last Updated: July 1, 2022

Record last verified: 2022-06

Locations

IN (1)