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

Study Overview
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Brief Summary
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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.

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

Conditions
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Acute Liver Failure

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Standard medical therapy with Plasma Exchange<br>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<br> <br> Other: Management of cerebral edema/intracranial hypertension:<br> <br> Other: Transfer to Intensive Care Unit<br> <br> Drug: Prophylactic Antibiotics<br> <br> Other: Intubation of trachea<br> <br> Other: Administration of mannitol or 3% saline for severe elevation of Intra Cranial Pressure<br> <br> Other: Volume Replacement<br> <br> Other: Pressor Support<br> <br> Drug: N-acetyl-L-cysteine<br> <br> Other: Correction of metabolic parameters<br> <br> Dietary Supplement: Correction of nutrition<br> <br> |
| Active Comparator: Standard medical therapy alone<br>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:<br> <br> Other: Transfer to Intensive Care Unit<br> <br> Drug: Prophylactic Antibiotics<br> <br> Other: Intubation of trachea<br> <br> Other: Administration of mannitol or 3% saline for severe elevation of Intra Cranial Pressure<br> <br> Other: Volume Replacement<br> <br> Other: Pressor Support<br> <br> Drug: N-acetyl-L-cysteine<br> <br> Other: Correction of metabolic parameters<br> <br> Dietary Supplement: Correction of nutrition<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 |