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

Not Applicable

Completed

• Conditions: Acute Liver Failure
• Interventions: Biological: Plasma Exchange; 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

• Registration Number: NCT02718079
• Lead Sponsor: Institute of Liver and Biliary Sciences, India

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-02-29
• Study First Submitted QC: 2016-03-22
• Study First Posted: 2016-03-24
• Study Start: 2016-12-30
• Primary Completion: 2018-10-08
• Study Completion: 2018-10-18
• Status Verified: 2019-11
• Last Update Submitted: 2019-11-18
• Last Update Posted: 2019-11-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard medical therapy with Plasma Exchange	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.
Standard medical therapy with Plasma Exchange	Transfer to Intensive Care Unit	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.
Standard medical therapy with Plasma Exchange	Prophylactic Antibiotics	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.
Standard medical therapy with Plasma Exchange	Intubation of trachea	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.
Standard medical therapy with Plasma Exchange	Administration of mannitol or 3% saline for severe elevation of Intra Cranial Pressure	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.
Standard medical therapy with Plasma Exchange	Volume Replacement	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.
Standard medical therapy with Plasma Exchange	Pressor Support	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.
Standard medical therapy with Plasma Exchange	N-acetyl-L-cysteine	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.
Standard medical therapy with Plasma Exchange	Correction of metabolic parameters	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.
Standard medical therapy with Plasma Exchange	Correction of nutrition	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.
Standard medical therapy alone	Transfer to Intensive Care Unit	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.
Standard medical therapy alone	Prophylactic Antibiotics	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.
Standard medical therapy alone	Intubation of trachea	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.
Standard medical therapy alone	Administration of mannitol or 3% saline for severe elevation of Intra Cranial Pressure	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.
Standard medical therapy alone	Volume Replacement	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.
Standard medical therapy alone	Correction of metabolic parameters	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.
Standard medical therapy alone	Correction of nutrition	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.
Standard medical therapy alone	Pressor Support	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.
Standard medical therapy alone	N-acetyl-L-cysteine	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.

Primary Outcome Measures

Name	Time	Method
Survival in both groups.	21 days

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Institute of liver and Biliary Sciences; 🇮🇳 New Delhi, Delhi, India