An Open-label Randomized Controlled Trial Comparing the Role of Therapeutic Plasma-exchange in Ameliorating Secondary Organ Dysfunctions in Patients With ACLF and Develop Biomarkers of Treatment Response

NCT06276907 | Not Yet Recruiting

• 1 other identifier: ILBS-ACLF-16
• Study Type: interventional
• Target: 190
• Locations: 1 country
• Sites: 1

Brief Summary

Rationale: Current understanding of the pathophysiology of ACLF suggests that unresolved injury, poor infection control, and liver regeneration result in persistent systemic inflammation and cytokine storm, which subsequently lead to systemic inflammatory response syndrome (SIRS) resulting in multiple organ failures, septic shock and deaths in ACLF. Nearly 74% of ACLF patients initially diagnosed without SIRS, sepsis, or organ failure developed SIRS by day 7 which increases the onset of secondary organ failure and sepsis with high short-term mortality. The emerging use of plasma exchange has shown some potential benefits in terms of dampening systemic inflammation and improvement of outcomes in some ACLF patients. However, there is currently no randomized controlled trial exploring the potential role in ameliorating secondary organ dysfunctions in patients with ACLF is not known. Hence in the current objective, we want to study the role of plasma exchange in the management of sec. organ failure in ACLF patients in a randomized controlled trial and identify the biomarker to access the treatment response to therapy.

Conditions

Acute on Chronic Liver Failure

Outcome Measures

Primary Outcomes (1)

• The AARC grading is done by AARC score the values of which vary from 5-15 , pts are divided into 3 grades i.e AARC score 5-7- grade 1, 8-10- grade 2, and AARC 11-15 as grade 3. Improvement in 1 grade is associated with 40% improvement in 28-day survival

  the measure is an ordinal variable with 3 categories as above (grade 1, 2 and 3) derived from AARC score from 5-15

  28 days

Secondary Outcomes (5)

• Transplant-free survival at 28-days

  28 days

• The impact of TPE on the progression or resolution of secondary organ failures at day 7, 14 and 28

  day 7, 14 and 28

• the development of infection at day 7 and 14 in patients who had no infection

  day 7 and day 14

• Duration of ICU and hospital stay

  28 days

• The proportion of patients developing adverse events will be compared between the two groups

  7 days

Study Arms (2)

Plasma Exchange

EXPERIMENTAL

On day 1 Response assessment will be done to assess the need for a second session from day 3-7 and subsequently every week till day 28. A minimum of 3 sessions would be considered in the first seven days. The duration of each session would be 3-4 hours. Patients with partial response (not meeting criteria for a complete response after 3 sessions) would be considered for additional sessions as decided by the treating physician until desired complete response, adverse effects, liver transplant, death, or clinical futility. The complete response will be defined as a sustained reduction in bilirubin and international normalized ratio without any clinical worsening requiring discontinuation of therapy. Failure of therapy would be defined as the development of adverse effects, new onset sepsis, or organ failure. In such patients, further sessions would be deferred. Blood access was established with a double-lumen catheter inserted into the patient's femoral or jugular vein.

Biological: Plasma Exchange

Standard Medical Treatment

ACTIVE COMPARATOR

Patients randomized to SMT Group will be given standard medical therapy (SMT) only included as per requirement.

Other: Standard Medical Treatment

Interventions

Plasma Exchange BIOLOGICAL

On day 1 Response assessment will be done to assess the need for a second session from day 3-7 and subsequently every week till day 28. A minimum of 3 sessions would be considered in the first seven days. The duration of each session would be 3-4 hours. Patients with partial response (not meeting criteria for a complete response after 3 sessions) would be considered for additional sessions as decided by the treating physician until desired complete response, adverse effects, liver transplant, death, or clinical futility. The complete response will be defined as a sustained reduction in bilirubin and international normalized ratio without any clinical worsening requiring discontinuation of therapy. Failure of therapy would be defined as the development of adverse effects, new onset sepsis, or organ failure. In such patients, further sessions would be deferred. Blood access was established with a double-lumen catheter inserted into the patient's femoral or jugular vein.

Plasma Exchange

Standard Medical Treatment OTHER

Patients randomized to SMT Group will be given standard medical therapy (SMT) only included as per requirement.

Standard Medical Treatment

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with ACLF with AARC grade 2 or more with or without single secondary organ failure.

You may not qualify if:

• \. Patients with age less than 18 years or more than 65 years
• Patients with HVOTO or EHPVO
• Hepatocellular carcinoma (beyond Milan) or any extrahepatic malignancy
• Active bleed (mucosal or variceal) or severe coagulopathy (platelets \<20,000 or INR\>4)
• Patients with refractory shock requiring norepinephrine \>0.5ug/kg/min
• Patients with retroviral infections
• Pregnancy or active breastfeeding
• Known severe cardiopulmonary diseases (structural or valvular heart disease, coronary artery disease, coronary pulmonary disease, chronic kidney disease)
• Lack of informed consent

Sponsors & Collaborators

• Institute of Liver and Biliary Sciences, India: lead

Study Sites (1)

Institute of Liver & Biliary Sciences

New Delhi, National Capital Territory of Delhi, 110070, India

Location

MeSH Terms

Conditions

Acute-On-Chronic Liver Failure

Interventions

Plasma Exchange

Condition Hierarchy (Ancestors)

Liver Failure, Acute; Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Blood Transfusion; Biological Therapy; Therapeutics; Plasmapheresis; Blood Component Removal; Sorption Detoxification; Extracorporeal Circulation; Surgical Procedures, Operative

Central Study Contacts

Dr Rakhi Maiwall, DM

CONTACT

01146300000; rakhi_2011@yahoo.co.in

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 2, 2024
• First Posted: February 26, 2024
• Study Start: March 1, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: February 26, 2024

Record last verified: 2024-02

Locations

IN (1)