Clinical trial NCT05700708: Point-of-Care Echocardiography to Assess Impact of Dynamic Cardiac Function, Renal and Cardiac Biomarkers in Cirrhosis With Refractory Ascites
Official title: Point-of-Care Echocardiography to Assess Impact of Dynamic Cardiac Function, Renal and Cardiac Biomarkers in Cirrhosis With Refractory Ascites
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Cirrhosis, Liver
Acute-On-Chronic Liver Failure
Refractory Ascites
Ascites
Acute Kidney Injury
Keywords: Ascites
Cirrhotic Cardiomyopathy
Acute kidney injury
Lead sponsor: PGIMER
Sponsor class: UNKNOWN
First posted: 2023-01-26
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Cirrhosis of any etiology, aged between 18-65 years, with Refractory Ascites definition as per International Ascites club.

1. Diuretic-resistant ascites
2. Diuretic-intractable ascites

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Cardiac output measurement by echocardiography after albumin
timeFrame: Day 0
measure: Cardiac output measurement by echocardiography after albumin
timeFrame: Day 1
measure: Cardiac output measurement by echocardiography after albumin
timeFrame: Day 2
measure: Cardiac output measurement by echocardiography after albumin
timeFrame: Day 3
Secondary outcomes:
measure: Change in Cystatin C and Neutrophil gelatinase associated lipocalin (NGAL) level
timeFrame: day 0
measure: Change in NT Pro brain natriuretic peptide (BNP) level
timeFrame: day 0
measure: Change in plasma renin activity level
timeFrame: day 0
measure: Change in Galectin-3 level
timeFrame: day 0
measure: IVC size and collapsibility changes after 20% albumin
timeFrame: Day 0
measure: IVC size and collapsibility changes after 20% albumin
timeFrame: Day 2
measure: Lung Ultrasound score change after 20% Albumin
timeFrame: Day 1
measure: IVC size and collapsibility changes after 20% albumin
timeFrame: Day 1
measure: Lung Ultrasound score change after 20% Albumin
timeFrame: Day 0
measure: Lung Ultrasound score change after 20% Albumin
timeFrame: Day 2
Other outcomes:
Locations:
city: Chandigarh
country: India
facility: PGIMER
state: Delhi
Study officials:
References:
citation: 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.
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.
citation: Cardenas A, Arroyo V. Refractory ascites. Dig Dis. 2005;23(1):30-8. doi: 10.1159/000084723.
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.
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.