Efficacy of Early Terlipressin Plus Albumin Therapy in Comparison to Standard Treatment for HRS-AKI in Acute-on-chronic Liver Failure.

NCT04416282 | Completed

• 1 other identifier: ILBS-ACLF-04
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

Acute on chronic liver failure (ACLF) is a distinct entity where, because of severe acute hepatic injury, a rapid loss of liver function develops in a patient with previous chronic liver disease(4). These patients have severe hepatic dysfunction, and outcome is defined by functional hepatic reserve and extent of extra-hepatic organ failures(5). Renal failure is a frequent extra-hepatic organ failure, and its presence is an independent prognostic marker for mortality(12). The pathophysiological basis of renal dysfunction in patients with ACLF is different compared to those with decompensated cirrhosis (DC)(6). Systemic inflammation is the hallmark of ACLF, characterized by a cytokine storm wherein there is an increase in both pro- and anti-inflammatory cytokines, such as interleukin (IL)-6, IL-8, IL-1β, and IL-10, leading to circulatory dysfunction and organ failure(3). These patients therefore have a higher incidence and progression of acute kidney injury (AKI). Diagnosis of HRS-AKI in ACLF currently requires 48 h of volume repletion with albumin and diuretic withdrawal. Therefore waiting for 48 hours to start treatment with terlipressin can be associated with worsening of AKI stage, worsening of ACLF stage and thereby suboptimal treatment response and high mortality despite treatment response. Therefore early initiation of terlipressin as continuous infusion after volume repletion with IV albumin in ACLF-AKI is safe and prevents AKI progression by splanchnic vasoconstriction and improved renal perfusion.

Conditions

Acute-On-Chronic Liver Failure; Hepatorenal Syndrome; Acute Kidney Injury

Outcome Measures

Primary Outcomes (1)

• Acute Kidney Injury reversal by day 7 in both groups

  Day 7

Secondary Outcomes (4)

• Mortality in both groups

  Day 28

• Mortality in both groups

  Day 90

• Progression or resolution of Organ failures

  Day 90

• Adverse Events in both groups

  Day 90

Study Arms (2)

Terlipressin + Albumin

EXPERIMENTAL

Injection terlipressin 2 mg/24 hours infusion + i/v albumin 1g/Kg/day

Drug: Terlipressin; Biological: Albumin

Albumin

ACTIVE COMPARATOR

i/v albumin 1g/Kg/day for next 36 hours f/b inj terlipressin 2mg/24 hours

Biological: Albumin

Interventions

Terlipressin DRUG

Injection terlipressin 2 mg/24 hours infusion

Terlipressin + Albumin

Albumin BIOLOGICAL

i/v albumin 1g/Kg/day

Albumin; Terlipressin + Albumin

Eligibility Criteria

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

You may qualify if:

• Age 18-65 years
• ACLF as per APASL criteria
• AKI at admission as defined by ICA-AKI criteria
• AKI stage 2/3 at 12 hour of admission

You may not qualify if:

• At Admission:
• Age \<18 years
• Patients on renal replacement therapy (RRT)
• Post renal or liver transplantation
• History of CAD, ischemic cardiomyopathy, PVD, ventricular arrhythmia
• Decompensated cirrhosis not fulfilling ACLF criteria
• Cirrhotics with AKI managed as outpatients
• Grade III/IV HE or Shock requiring inotropes or patients on mechanical ventilator at time of randomization
• In-hospital new AKI
• Active urinary sediments - 2+ albumin or above, dysmorphic RBCs
• Known CKD, obstructive uropathy
• Lack of informed consent
• Prior intolerance or S/E to Terlipressin or albumin
• At 12 Hour before randomization:
• Regression of AKI (\>0.3 mg/dl) above baseline after IV albumin (20% 40 gm) + IV Crystalloids 500 ml therapy for 12 hours

Sponsors & Collaborators

• Institute of Liver and Biliary Sciences, India: lead

Study Sites (1)

Institute of Liver & Biliary Sciences

New Delhi, National Capital Territory of Delhi, 110070, India

Location

MeSH Terms

Conditions

Acute-On-Chronic Liver Failure; Hepatorenal Syndrome; Acute Kidney Injury

Interventions

Terlipressin; Albumins

Condition Hierarchy (Ancestors)

Liver Failure, Acute; Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Renal Insufficiency

Intervention Hierarchy (Ancestors)

Lypressin; Vasopressins; Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2020
• First Posted: June 4, 2020
• Study Start: June 22, 2020
• Primary Completion: June 10, 2022
• Study Completion: June 10, 2022
• Last Updated: April 6, 2023

Record last verified: 2023-04

Locations

IN (1)