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

Cirrhosis, Liver Clinical Trial

Official title:

To Compare 20% Albumin vs. Balanced Salt Solution as Resuscitation Fluid and Identify Fluid Responsiveness Criteria in Critically Ill Patients With Cirrhosis With Sepsis Induced Hypotension; a Prospective Randomized Controlled Trial.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05441878
• Other study ID #: IEC/11/2019/1496
• Status: Recruiting
• Phase: Phase 4
• Start date: August 15, 2020
• Est. completion date: December 2023

Study information

• Verified date: June 2022
• Source: Postgraduate Institute of Medical Education and Research
• Contact: Madhumita Premkumar, DM
• Phone: 01722756344
• Email: drmadhumitap[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 .

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: December 2023
• Est. primary completion date: October 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Acute-On-Chronic Liver Failure
• Cirrhosis, Liver
• End Stage Liver Disease
• Fibrosis
• Hypotension
• Hypovolemia
• Liver Cirrhosis
• Liver Failure
• Shock
• Shock Hypovolemic
• Shock, Septic

Intervention

Drug:
• 20% albumin
Albumin arm for resuscitation fluid
• Balanced salt solution
Only Balanced salt solution will be used.

Locations

Country	Name	City	State
India	Postgraduate Institute of Medical Education and Research	Chandigarh

Sponsors (1)

Lead Sponsor	Collaborator
Postgraduate Institute of Medical Education and Research

Country where clinical trial is conducted

India, 

References & Publications (7)

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. — View Citation

Borzio M, Salerno F, Piantoni L, Cazzaniga M, Angeli P, Bissoli F, Boccia S, Colloredo-Mels G, Corigliano P, Fornaciari G, Marenco G, Pistarà 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. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

Navasa M, Fernández J, Rodés J. Bacterial infections in liver cirrhosis. Ital J Gastroenterol Hepatol. 1999 Oct;31(7):616-25. Review. — View Citation

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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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.
Primary	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
Primary	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
Primary	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.
Primary	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
Primary	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	Urinary marker of AKI (NGal)		At enrolment
Secondary	Change in urinary markers of AKI (NGal)		At 24 hours.
Secondary	Change in urinary markers of AKI(NGal)		At 48 hours.
Secondary	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	To compare the vasopressor requirement in patients with cirrhosis and sepsis induced hypotension	At enrolment
Secondary	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	To compare the vasopressor requirement in patients with cirrhosis and sepsis induced hypotension	At 24 hours