Point-of-Care Echocardiography to Assess Impact of Dynamic Cardiac Function, Renal and Cardiac Biomarkers in Cirrhosis With Refractory Ascites

Acute Kidney Injury Clinical Trial

Official title:

Point-of-Care Echocardiography to Assess Impact of Dynamic Cardiac Function, Renal and Cardiac Biomarkers in Cirrhosis With Refractory Ascites

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05700708
• Other study ID #: NK-2020-2141
• Status: Recruiting
• Start date: November 15, 2022
• Est. completion date: July 15, 2024

Study information

• Verified date: September 2023
• Source: Postgraduate Institute of Medical Education and Research
• Contact: Madhumita Premkumar
• Phone: 01722754777
• Email: drmadhumitap[@]gmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Point-of-care echocardiography (POC-Echo) is used to determine left ventricular systolic and diastolic dysfunction (LVDD), inferior vena cava (IVC) dynamics and volume status in cirrhosis and Acute-on-chronic liver failure ACLF accurately.

We will assess IVC dynamics, LV systolic function [LV ejection fraction (EF) & cardiac output (CO)], and diastolic dysfunction (E/e', e' and E/A ratio) and urinary biomarkers (cystatin C and NGAL) in patients with cirrhosis and Refractory Ascites.

Description:

The decrease in systemic vascular resistance (SVR) and redistribution of blood volume with reduced intravascular volume compartment and third space fluid losses. Systemic vasodilatation is compensated by an increase in cardiac output (CO) in the initial stages of compensated cirrhosis. However, as the stage of liver cirrhosis progresses to decompensation, more prominent arterial vasodilatation and reduced SVR leads to a fall in CO. Thus, the cardiac homeostat is reset in a cirrhotic hyperdynamic circulation, wherein an increased heart rate, and therefore, increased cardiac output will no longer be able to compensate for the reduced mean arterial pressure (MAP), and decreased blood volumes in central venous territories.18 Consequent activation of vasoconstrictor systems including renin-angiotensin-aldosterone, vasopressin and the sympathetic nervous system comes into play to maintain the intravascular blood volume and pressure. These compensatory pathways cause an increase in sodium and water retention resulting in refractory ascites and hepatorenal syndrome (HRS). In critically ill patients with cirrhosis, the limited cardiac reserve is further stressed, CCM and heart failure may be diagnosed for the first time when the patient develops sepsis or septic shock.

Point-of-care echocardiography (POC-Echo) is used to determine left ventricular systolic and diastolic dysfunction (LVDD), inferior vena cava (IVC) dynamics and volume status in cirrhosis accurately. We will assess IVC dynamics, LV systolic function [LV ejection fraction (EF) & cardiac output (CO)], and diastolic dysfunction (E/e', e' and E/A ratio) in patients with cirrhosis ACLF and refractory ascites

Definition of CCM is as per updated CCMC criteria of 2020.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: July 15, 2024
• Est. primary completion date: November 15, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Cirrhosis of any Etiology

• Patient with Refractory Ascites

Exclusion Criteria:

• Hepatocellular carcinoma

• Patients with active variceal bleeding

• HIV or severe immunocompromised state

• Chronic kidney disease (CKD) on renal replacement therapy (RRT),

• Previous transjugular intra hepatic portosystemic shunt (TIPS)

• Porto-pulmonary hypertension,

• Coronary artery disease

• Congenital or valvular heart disease

• Prosthetic cardiac valves

Related Conditions & MeSH terms

• Acute Kidney Injury
• Acute-On-Chronic Liver Failure
• Ascites
• Cirrhosis, Liver
• End Stage Liver Disease
• Fibrosis
• Liver Cirrhosis
• Liver Failure
• Refractory Ascites

Intervention

Diagnostic Test:
• Echocardiographic assessment
POC-Echocardiography to assess dynamic changes in cardiac output to assess therapeutic responses with albumin, midodrine, diuretics and domiciliary albumin

Locations

Country	Name	City	State
India	PGIMER	Chandigarh	Delhi

Sponsors (1)

Lead Sponsor	Collaborator
Postgraduate Institute of Medical Education and Research

Country where clinical trial is conducted

India, 

References & Publications (5)

Adebayo D, Neong SF, Wong F. Refractory Ascites in Liver Cirrhosis. Am J Gastroenterol. 2019 Jan;114(1):40-47. doi: 10.1038/s41395-018-0185-6. — View Citation

Cardenas A, Arroyo V. Refractory ascites. Dig Dis. 2005;23(1):30-8. doi: 10.1159/000084723. — View Citation

Izzy M, VanWagner LB, Lin G, Altieri M, Findlay JY, Oh JK, Watt KD, Lee SS; Cirrhotic Cardiomyopathy Consortium. Redefining Cirrhotic Cardiomyopathy for the Modern Era. Hepatology. 2020 Jan;71(1):334-345. doi: 10.1002/hep.30875. Epub 2019 Oct 11. Erratum — View Citation

Larrue H, Vinel JP, Bureau C. Management of Severe and Refractory Ascites. Clin Liver Dis. 2021 May;25(2):431-440. doi: 10.1016/j.cld.2021.01.010. Epub 2021 Mar 11. — View Citation

Salerno F, Guevara M, Bernardi M, Moreau R, Wong F, Angeli P, Garcia-Tsao G, Lee SS. Refractory ascites: pathogenesis, definition and therapy of a severe complication in patients with cirrhosis. Liver Int. 2010 Aug;30(7):937-47. doi: 10.1111/j.1478-3231.2010.02272.x. Epub 2010 May 21. Erratum In: Liver Int. 2010 Sep;30(8):1244. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cardiac output measurement by echocardiography after albumin	Echocardiographic assessment of cardiac output in L/min will be recorded at least 3 time points, day 0, day 1 and day 2.; The cardiac output at 3 days after enrollment and albumin therapy will also be documented. The Doppler velocity time integral (VTI) method in estimating stroke volume and cardiac output correlates well with results of concurrent thermodilution cardiac output determinations in patients without significant left-sided valvular regurgitation.; Cardiac output(CO), Stroke volume (SV), Heart rate (HR); CO = [SV * HR]/ 1000	Day 0
Primary	Cardiac output measurement by echocardiography after albumin	Echocardiographic assessment of cardiac output in L/min will be recorded at least 3 time points, day 0, day 1 and day 2.; The cardiac output at 3 days after enrollment and albumin therapy will also be documented. The Doppler velocity time integral (VTI) method in estimating stroke volume and cardiac output correlates well with results of concurrent thermodilution cardiac output determinations in patients without significant left-sided valvular regurgitation.; Cardiac output(CO), Stroke volume (SV), Heart rate (HR); CO = [SV * HR]/ 1000	Day 1
Primary	Cardiac output measurement by echocardiography after albumin	Echocardiographic assessment of cardiac output in L/min will be recorded at least 3 time points, day 0, day 1 and day 2.; The cardiac output at 3 days after enrollment and albumin therapy will also be documented. The Doppler velocity time integral (VTI) method in estimating stroke volume and cardiac output correlates well with results of concurrent thermodilution cardiac output determinations in patients without significant left-sided valvular regurgitation.; Cardiac output(CO), Stroke volume (SV), Heart rate (HR); CO = [SV * HR]/ 1000	Day 2
Primary	Cardiac output measurement by echocardiography after albumin	Echocardiographic assessment of cardiac output in L/min will be recorded at least 3 time points, day 0, day 1 and day 2.; The cardiac output at 3 days after enrollment and albumin therapy will also be documented. The Doppler velocity time integral (VTI) method in estimating stroke volume and cardiac output correlates well with results of concurrent thermodilution cardiac output determinations in patients without significant left-sided valvular regurgitation.; Cardiac output(CO), Stroke volume (SV), Heart rate (HR); CO = [SV * HR]/ 1000	Day 3
Secondary	Change in Cystatin C and Neutrophil gelatinase associated lipocalin (NGAL) level		day 0
Secondary	Change in NT Pro brain natriuretic peptide (BNP) level		day 0
Secondary	Change in plasma renin activity level		day 0
Secondary	Change in Galectin-3 level		day 0
Secondary	IVC size and collapsibility changes after 20% albumin	IVC maximum and Minimum diameter and collapsibility index determined by percentage change in IVC diameter will be recorded.	Day 0
Secondary	IVC size and collapsibility changes after 20% albumin	IVC maximum and Minimum diameter and collapsibility index determined by percentage change in IVC diameter will be recorded.	Day 2
Secondary	Lung Ultrasound score change after 20% Albumin		Day 1
Secondary	IVC size and collapsibility changes after 20% albumin	IVC maximum and Minimum diameter and collapsibility index determined by percentage change in IVC diameter will be recorded.	Day 1
Secondary	Lung Ultrasound score change after 20% Albumin		Day 0
Secondary	Lung Ultrasound score change after 20% Albumin		Day 2