High-Volume Plasma Exchange Versus Standard Medical Treatment in Patients With Acute Liver Failure

High-Volume Plasma Exchange Versus Standard Medical Treatment in Patients With Acute Liver Failure-A Prospective Randomized Pilot Trial

The study will be conducted on patients admitted to Department of Hepatology from Jan 2016 to Jan 2018 at Institute of Liver & Biliary Sciences, New Delhi. Study group will comprise of patients with acute liver failure (ALF) who have no option for liver transplant (due to any reason) or have contraindications for liver transplant or have no prospective living donor and will be assessed for enrollment in the trial.

Study Overview

• Status: Completed
• Conditions: Acute Liver Failure
• Intervention / Treatment: Biological: Plasma Exchange; Other: Management of cerebral edema/intracranial hypertension:; Other: Transfer to Intensive Care Unit; Drug: Prophylactic Antibiotics; Other: Intubation of trachea; Other: Administration of mannitol or 3% saline for severe elevation of Intra Cranial Pressure; Other: Volume Replacement; Other: Pressor Support; Drug: N-acetyl-L-cysteine; Other: Correction of metabolic parameters; Dietary supplement: Correction of nutrition

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• India
  • Delhi
    • New Delhi, Delhi, India, 110070
      • Institute of liver and Biliary Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with acute liver failure defined as : Patients with jaundice which is complicated by encephalopathy and coagulopathy within 4 weeks of the onset of jaundice and without underlying chronic liver disease.

Exclusion Criteria:

• Age <12 or > 75 years
• Hepato-Cellular Carcinoma
• Active untreated Sepsis/DIC
• Any evidence of active bleed secondary to coagulopathy
• Hemodynamic instability requiring high dose of Vasopressors
• Coma of non-hepatic origin.
• Pregnancy
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Standard medical therapy with Plasma Exchange; Plasma Exchange will be performed for consecutive days. Standard medical therapy included as per requirement,management of cerebral edema/intracranial hypertension: transfer to ICU,prophylactic antibiotics, intubation of trachea (as required),administration of mannitol or 3% saline for severe elevation of Intra Cranial Pressure,volume replacement and pressor support (norepinephrine, vasopressin) as needed, NAC, correction of metabolic parameters and nutrition.	Biological: Plasma Exchange; Other: Management of cerebral edema/intracranial hypertension: Other: Transfer to Intensive Care Unit; Drug: Prophylactic Antibiotics; Other: Intubation of trachea; Other: Administration of mannitol or 3% saline for severe elevation of Intra Cranial Pressure; Other: Volume Replacement; Other: Pressor Support; Drug: N-acetyl-L-cysteine; Other: Correction of metabolic parameters; Dietary supplement: Correction of nutrition
Active Comparator: Standard medical therapy alone; Standard medical therapy included as per requirement,management of cerebral edema/intracranial hypertension: transfer to ICU,prophylactic antibiotics, intubation of trachea (as required),administration of mannitol or 3% saline for severe elevation of Intra Cranial Pressure,volume replacement and pressor support (norepinephrine, vasopressin) as needed, NAC, correction of metabolic parameters and nutrition.	Other: Management of cerebral edema/intracranial hypertension: Other: Transfer to Intensive Care Unit; Drug: Prophylactic Antibiotics; Other: Intubation of trachea; Other: Administration of mannitol or 3% saline for severe elevation of Intra Cranial Pressure; Other: Volume Replacement; Other: Pressor Support; Drug: N-acetyl-L-cysteine; Other: Correction of metabolic parameters; Dietary supplement: Correction of nutrition

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Survival in both groups.	21 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Intensive Care Unit stay in both groups.		21 days
Improvement in SIRS (Systemic Inflammatory Response Syndrome) score.		48 hours
Improvement in SIRS (Systemic Inflammatory Response Syndrome) score.		day 5
Improvement in SIRS (Systemic Inflammatory Response Syndrome) score.		day 7
Improvement in SOFA (Sequential Organ Failure Assessment) score.		48 hours
Improvement in SOFA (Sequential Organ Failure Assessment) score.		day 5
Improvement in SOFA (Sequential Organ Failure Assessment) score.		day 7
Improvement in APACHE II (Acute Physiology and Chronic Health Evaluation) score.		48 hours
Improvement in APACHE II (Acute Physiology and Chronic Health Evaluation) score.		Day 5
Improvement in APACHE II (Acute Physiology and Chronic Health Evaluation) score.		Day 7
Effect on systemic haemodynamics in both groups.	Effect is defined as resolution of SIRS (Systemic Inflammatory Response Syndrome).	24 hours
Effect on systemic haemodynamics in both groups.	Effect is defined as resolution of SIRS (Systemic Inflammatory Response Syndrome).	48 hours
Pro inflammatory cytokines profile in both groups.		1 hour
Serum Endotoxin levels in both groups.		1 hour

Collaborators and Investigators

• Sponsor: Institute of Liver and Biliary Sciences, India
• Investigators: Principal Investigator: Dr Rakhi Maiwall, DM, Institute of liver and Biliary Sciences

Publications and helpful links

General Publications

• Maiwall R, Bajpai M, Singh A, Agarwal T, Kumar G, Bharadwaj A, Nautiyal N, Tevethia H, Jagdish RK, Vijayaraghavan R, Choudhury A, Mathur RP, Hidam A, Pati NT, Sharma MK, Kumar A, Sarin SK. Standard-Volume Plasma Exchange Improves Outcomes in Patients With Acute Liver Failure: A Randomized Controlled Trial. Clin Gastroenterol Hepatol. 2022 Apr;20(4):e831-e854. doi: 10.1016/j.cgh.2021.01.036. Epub 2021 Jan 29.

Study record dates

Study Major Dates

• Study Start (Actual): December 30, 2016
• Primary Completion (Actual): October 8, 2018
• Study Completion (Actual): October 18, 2018

Study Registration Dates

• First Submitted: February 29, 2016
• First Submitted That Met QC Criteria: March 22, 2016
• First Posted (Estimate): March 24, 2016

Study Record Updates

• Last Update Posted (Actual): November 20, 2019
• Last Update Submitted That Met QC Criteria: November 18, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Liver Failure; Hepatic Insufficiency; Liver Failure, Acute; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Protective Agents; Natriuretic Agents; Diuretics, Osmotic; Diuretics; Respiratory System Agents; Antioxidants; Antidotes; Free Radical Scavengers; Expectorants; Mannitol; Anti-Bacterial Agents; Acetylcysteine; N-monoacetylcystine
• Other Study ID Numbers: ILBS-ALF-03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No