To Assess the Efficacy of High-Volume Plasma Exchange and GCSF Versus GCSF Alone in Patients of Acute on Chronic Liver Failure (ACLF).

To Assess the Efficacy of High-Volume Plasma Exchange and GCSF Versus GCSF Alone in Patients of Acute on Chronic Liver Failure (ACLF)-A Randomized Controlled Trial.

Study design-Open label randomized controlled trial

Study period-2 years

Study population-All patients of ACLF admitted to ILBS for a period of two years from Feb 2017 to Dec 2018

All the patients of ACLF will receive standard medical therapy and will be randomized within 48 hours of admission into three groups after screening for exclusion and inclusion criteria.(1:2:2) Group A-Standard Medical Therapy only Group B-Standard Medical therapy + Plasma exchange + GCSF Group C-Standard Medical Therapy + GCSF

Study Overview

• Status: Withdrawn
• Conditions: Acute-On-Chronic Liver Failure
• Intervention / Treatment: Drug: Standard Medical Therapy; Biological: Plasma Exchange; Biological: GCSF

• Study Type: Interventional
• 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: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

- All consecutive patients in age group of 18-70 years with acute on chronic liver failure as defined by APASL criteria shall be included in the study.Only those patients who wish to be enrolled in the trial shall be included in the study.

Exclusion Criteria:

1. Steroid eligible patients with severe alcoholic hepatitis
2. Cirrhosis of liver with previous history of decompensation
3. Patients with severe cardiopulmonary disease
4. Pregnancy
5. Human Immmunodeficiency Virus infection
6. Hepatocellular carcinoma or extrahepatic malignancy
7. Chronic renal insufficiency on treatment with haemodialysis
8. Uncontrolled bleed or patients in disseminated intravascular coagulopathy
9. Patient with expected survival of less than 48 hours
10. Patients with moderate-severe acute respiratory distress syndrome
11. Hemodynamic instability with noradrenaline requirement of more than >0.5ug/kg/min or requirement of dual vasopressors
12. Patients with leukemoid reaction or total leucocyte count > 40,000/mm3
13. Patients diagnosed with Hemophagocytic Lymphohistiocytosis
14. Patients with known hypersensitivity to Granulocyte colony stimulating factor

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard Medical Therapy; The patients in group A will be given standard medical therapy only as per requirement. Lactulose, bowel wash, albumin, terlipressin, antibiotics and anti-virals in hepatitis B reactivation will be continued and recorded.	Drug: Standard Medical Therapy; The patients in group A will be given standard medical therapy only as per requirement. Lactulose, bowel wash, albumin, terlipressin, antibiotics and anti-virals in hepatitis B reactivation will be continued and recorded.
Experimental: Standard Medical Therapy + Plasma exchange + GCSF; The patients in group B shall be given GCSF in a dose of 5 ug/kg/day on day 1,2,3,4,5 followed by every 3rd day till day 28 along with alternate day high volume plasma exchange sessions till a maximum of ten sessions.	Drug: Standard Medical Therapy; The patients in group A will be given standard medical therapy only as per requirement. Lactulose, bowel wash, albumin, terlipressin, antibiotics and anti-virals in hepatitis B reactivation will be continued and recorded.; Biological: Plasma Exchange; High volume plasma exchange sessions till a maximum of ten sessions.; Biological: GCSF; The GCSF in a dose of 5 ug/kg/day on day 1,2,3,4,5 followed by every 3rd day till day 28
Experimental: Standard Medical Therapy + GCSF; The patients in this will be given standard medical therapy only as per requirement. Lactulose, bowel wash, albumin, terlipressin, antibiotics and anti-virals in hepatitis B reactivation will be continued and recorded. The GCSF in a dose of 5 ug/kg/day on day 1,2,3,4,5 followed by every 3rd day till day 28	Drug: Standard Medical Therapy; The patients in group A will be given standard medical therapy only as per requirement. Lactulose, bowel wash, albumin, terlipressin, antibiotics and anti-virals in hepatitis B reactivation will be continued and recorded.; Biological: GCSF; The GCSF in a dose of 5 ug/kg/day on day 1,2,3,4,5 followed by every 3rd day till day 28

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Transplant free survival	28 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Improvement in biochemical parameter which is defined as > 20% reduction from baseline in both groups	Day 14
Improvement in biochemical parameter which is defined as > 20% reduction from baseline in both groups	Day 28
Improvement in clinical parameters which is defined as > 20% reduction from baseline in both groups	Day 14
Improvement in clinical parameters which is defined as > 20% reduction from baseline in both groups	Day 28
Improvement in APACHEII (by 2 points )	2 years
Improvement in MELD (by 2 points )	2 years
Improvement in SIRS by 2 points	2 years
Improvement in SOFA (by 2 points )	2 years
Incidence of new onset sepsis and SIRS in both groups.	Day 28
Side effects of therapy in both groups	2 years

Collaborators and Investigators

• Sponsor: Institute of Liver and Biliary Sciences, India

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2017
• Primary Completion (Anticipated): April 25, 2019
• Study Completion (Anticipated): April 25, 2019

Study Registration Dates

• First Submitted: April 20, 2017
• First Submitted That Met QC Criteria: May 19, 2017
• First Posted (Actual): May 22, 2017

Study Record Updates

• Last Update Posted (Actual): December 3, 2018
• Last Update Submitted That Met QC Criteria: November 30, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Liver Failure, Acute; End Stage Liver Disease; Liver Failure; Hepatic Insufficiency; Acute-On-Chronic Liver Failure
• Other Study ID Numbers: ILBS-ACLF-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No