To Evaluate the Safety and Efficacy of Preemptive Administration of Continuous Renal Replacement Therapy in Patients With Acute Liver Failure With Cerebral Edema

NCT04991259 | Unknown

• 1 other identifier: ILBS-ALF-05
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

In this prospective randomized controlled trial, investigator aim to evaluate the impact of early initiation of CRRT on outcomes in patients with acute liver failure with cerebral edema and hyperammonemia in improving cerebral edema and clinical outcomes. Investigator also aim to evaluate the effects of early initiation of CRRT on systemic hemodynamics (cardiac output and systemic vascular resistive index, extravascular lung water and lung permeability index), endothelial function and coagulation, microcirculation (as assessed by lactate clearance and central venous oxygen saturation), mitochondrial function. Patients with ALF who meet the inclusion and exclusion criteria. Group 1: CRRT initiation within the first 12 hours Group 2: CRRT would be initiated i) In patients with worsening hyperammonemia despite two sessions of plasma-exchange ii) Patients meeting renal indications (hyperkalemia, volume overload, oliguria or metabolic acidosis etc)

Conditions

Acute Liver Failure

Outcome Measures

Primary Outcomes (1)

• Transplant free survival

  Day 21

Secondary Outcomes (21)

• Improvement in cerebral edema and hepatic encephalopathy

  Day 5

• Improvement in cerebral edema and hepatic encephalopathy

  Day 14

• Duration of mechanical ventilation in both groups

  28 days

• Duration of ICU stay in both groups

  28 days

• Impact on arterial lactate

  6 hours

Study Arms (2)

Preemptive CRRT

EXPERIMENTAL

In patients randomized to early CRRT, CRRT would be initiated within 12 hours of randomization.

Procedure: Continuous Renal Replacement Therapy (CRRT)

Standard Medical Treatment

ACTIVE COMPARATOR

In patients randomized to SMT group, CRRT would be initiated as per the existing standard protocol. 1. in patients with worsening hyperammonemia despite two sessions of plasma-exchange 2. patients meeting renal indications (hyperkalemia, volume overload, oliguria or metabolic acidosis etc).

Procedure: Continuous Renal Replacement Therapy (CRRT); Other: Standard Medical Treatment

Interventions

Continuous Renal Replacement Therapy (CRRT) PROCEDURE

Continuous renal replacement therapy will be administered as continuous venovenous hemodiafiltration (CVVHDF) using Prisma and Prismaflex (Gambro) devices, with blood flows ranging from 150-180 mL/hr and target effluent rates of 20 - 25 mL/kg/hr. Anticoagulation was not used during dialysis. CRRT would be continued until resolution of cerebral edema and in decrease in ammonia levels below 150 ug/dl or in those who develop adverse effects of therapy.

Preemptive CRRT; Standard Medical Treatment

Standard Medical Treatment OTHER

In the L- ICU, patients will be managed by a multidisciplinary team. Intubation and ventilation will be undertaken for standard indications in addition to the development of grade 3 encephalopathy or evidence of cerebral edema on CT-scan. Fluid management will be done with crystalloids, with the use of colloids (5% albumin) in patients with severe hypoalbuminemia (serum albumin less than 2.5gm/dl). Norepinephrine will be the primary vasopressor used to target a mean arterial pressure of 65-70 mm of Hg. with adjunctive use of intravenous low dose hydrocortisone and vasopressin in patients not responsive to initial therapy.

Standard Medical Treatment

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- Patients with acute liver failure defined patients with jaundice which is complicated by encephalopathy and coagulopathy within 4 weeks of the onset of jaundice and without underlying chronic liver disease with documented cerebral edema on CT-scan and arterial ammonia \>150 ug/dL.

You may not qualify if:

• Age \<18 or \> 70 years
• Hepatocellular Carcinoma
• Active untreated Sepsis/DIC
• Hemodynamic instability requiring high dose of vasopressors
• Post-resection and malignancy related liver failure
• Coma of non-hepatic origin
• Patients with post renal obstructive AKI, AKI suspected due to glomerulonephritis, interstitial nephritis or vasculitis based on clinical history and urine analysis
• Patients already meeting emergency criteria for immediate initiation of dialysis at the time of randomization (serum potassium\>6 meq/lt, metabolic acidosis ph\<7.12, acute pulmonary edema, severe volume overload with hypoxemia non-responsive to diuretic treatment)
• Patients transferred from other hospitals who have already been on hemodialysis before their arrival in the intensive care unit
• Extremely moribund patients with an expected life expectancy of less than 24 hours
• Pregnancy related liver failure
• Patients with significant renal dysfunction meeting absolute criteria for initiation of dialysis
• Comorbidities associated with poor outcome (Extrahepatic neoplasia, severe cardiopulmonary disease defined by a New York Heart Association score \>3, or oxygen/steroid-dependent chronic obstructive pulmonary disease)
• Patients being taken up for liver transplant
• Refusal to participate in the study.

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

Liver Failure, Acute

Interventions

Continuous Renal Replacement Therapy

Condition Hierarchy (Ancestors)

Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Renal Replacement Therapy; Therapeutics; Extracorporeal Circulation; Surgical Procedures, Operative

Central Study Contacts

Dr Rakhi Maiwall, DM

CONTACT

01146300000; rakhi_2011@yahoo.co.in

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 25, 2021
• First Posted: August 5, 2021
• Study Start: August 10, 2021
• Primary Completion: June 30, 2023
• Study Completion: June 30, 2023
• Last Updated: August 17, 2021

Record last verified: 2021-06

Locations

IN (1)