Plasma Exchange in Acute on Chronic Liver Failure

NCT ID: NCT04051437

Last Updated: 2019-08-09

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 130 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-08-15
• Study Completion Date: 2020-03-31

Brief Summary

Acute on chronic liver failure (ACLF) is a distinct syndrome in patients with chronic liver disease with rapid clinical deterioration and has high short term mortality within one month.Despite aggressive clinical care, only half of the patients could survive an episode of ACLF. The investigators hypothesized that the early treatment with therapeutic plasma exchange with plasma and albumin in ACLF patients might improve overall survival in carefully selected patients by removing cytokines, chemokines and toxic substances.

Detailed Description

Acute on chronic liver failure (ACLF) lacks a consensus definition and definitive management approaches. The various management strategies include treatment of acute insult, support of multiple organ systems and disease-specific medications such as antivirals for hepatitis B, steroids for alcoholic hepatitis, and autoimmune hepatitis. Despite aggressive clinical care, only half of the patients could survive an episode of ACLF. ACLF is a dynamic condition and has specific time-related disease course. Majority of patients of the patients attain their final grade of ACLF between 3 rd and 7th day and makes it an ideal time to assess the prognosis. Recently, liver transplantation option also explored in patients not responding to standard medical care and appeared promising. Early liver transplantation is considered if the baseline model for end-stage liver disease (MELD) score > 28, Asia pacific association for the study of the liver (APASL) ACLF Research Consortium (AARC) score of > 10, advanced hepatic encephalopathy in the absence of organ failures or overt sepsis. However, liver transplantation is feasible only in 25% cases and approximately 67% waitlist mortality. Treating ACLF patients early in the disease course, i.e., window period, may prevent multiorgan dysfunction and improve outcomes. Therefore, these alternative modalities can act as bridging to liver transplantation and hasten the spontaneous liver regeneration and hence, transplant-free recovery in some patients.

Plasma exchange has been shown to reduce cytokines, inflammatory mediators, and damage-associated molecular patterns. The early experience of therapeutic plasma exchange in patients with hepatitis B ACLF shows a survival benefit compared to standard of care. Changes in albumin quantity and quality are noted in patients with cirrhosis. An increase in oxidized albumin, ischemia-modified albumin, and albumin dimerization is observed ACLF patients and changes are more pronounced compared to cirrhotic patients. These changes are well correlated with short and long term mortality.

Hence the investigators hypothesized that the early treatment with therapeutic plasma exchange with plasma and albumin in ACLF patients improves overall survival in carefully selected patients.

Conditions

Cirrhosis, Liver; Acute-On-Chronic Liver Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Plasma exchange

The consented patients will receive standard medical management with sessions of single volume plasma exchange with fresh frozen plasma and 5% human albumin.Plasma exchange session will be done on an alternate day to a maximum of 5 procedures.

Group Type: EXPERIMENTAL

Plasma exchange

Intervention Type: PROCEDURE

During each plasma exchange session 3-4lt (1.2-1.3 times of plasma volume) of plasma will be exchanged with fresh frozen plasma and 5% albumin. Plasma exchange session will be done on an alternate day to a maximum of 5 procedures. PLEX will be discontinued if the patients Shows sustained clinical improvement, Receive liver transplantation, Refuses further PLEX session No improvement in clinical condition Intolerant to PLEX procedure

Standard medical treatment

The consented patients will receive standard medical treatment which includes adequate nutrition (35-45 Kcal/Kg with 1.5gm/Kg protein) diuretics, anti HE measures, appropriate antibiotics for infections, entecavir 0.5 mg once daily for hepatitis B, and steroids for autoimmune hepatitis.

Group Type: ACTIVE_COMPARATOR

Standard medical treatment

Intervention Type: DRUG

The consented patients will receive standard medical treatment which includes adequate nutrition (35-45 Kcal/Kg with 1.5gm/Kg protein) diuretics, anti HE measures, appropriate antibiotics for infections,tablet entecavir 0.5 mg once daily for hepatitis B, and steroids for autoimmune hepatitis.

Interventions

Plasma exchange

During each plasma exchange session 3-4lt (1.2-1.3 times of plasma volume) of plasma will be exchanged with fresh frozen plasma and 5% albumin. Plasma exchange session will be done on an alternate day to a maximum of 5 procedures. PLEX will be discontinued if the patients Shows sustained clinical improvement, Receive liver transplantation, Refuses further PLEX session No improvement in clinical condition Intolerant to PLEX procedure

Intervention Type: PROCEDURE

Standard medical treatment

The consented patients will receive standard medical treatment which includes adequate nutrition (35-45 Kcal/Kg with 1.5gm/Kg protein) diuretics, anti HE measures, appropriate antibiotics for infections,tablet entecavir 0.5 mg once daily for hepatitis B, and steroids for autoimmune hepatitis.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients diagnosed with ACLF as per APASL criteria with AARC score of ≥8

Exclusion Criteria

1. Uncontrolled sepsis

2. Septic shock requiring inotropes despite fluid resuscitation

3. Active or recent bleeding (unless controlled for >48 hours).

4. Severe thrombocytopenia (≤20×10^9/L)

5. Acute kidney injury with Creatinine > 2 or the need of RRT

6. Respiratory failure (Severe ARDS)

7. Chronic kidney disease

8. Hepatocellular carcinoma outside Milan criteria (1 nodule ≤5 cm or 3 nodules ≤3 cm)

9. HIV infection

10. Pregnancy

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Asian Institute of Gastroenterology, India

OTHER

Sponsor Role: lead

Responsible Party

Dr. Pramod Kumar

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Central Contacts

Pramod Kumar, MD

Role: CONTACT

dapramod@gmail.com

+91-9814933544

Other Identifiers

AIG/IEC34/07.2019-08

Identifier Type: -

Identifier Source: org_study_id