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

Sponsor

Institute of Liver and Biliary Sciences, India (Other)

Overall Status

Completed

CT.gov ID

NCT02718079

Collaborator

(none)

Enrollment

Location

Arms

21.6

Actual Duration (Months)

1.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Liver Failure	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	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Dec 30, 2016

Actual Primary Completion Date :

Oct 8, 2018

Actual Study Completion Date :

Oct 18, 2018

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Survival in both groups. [21 days]

Secondary Outcome Measures

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. [24 hours]
Effect is defined as resolution of SIRS (Systemic Inflammatory Response Syndrome).
Effect on systemic haemodynamics in both groups. [48 hours]
Effect is defined as resolution of SIRS (Systemic Inflammatory Response Syndrome).
Pro inflammatory cytokines profile in both groups. [1 hour]
Serum Endotoxin levels in both groups. [1 hour]

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.