National Collaborative Centre for Hepatic Regenerative Medicine (NC-CHRM): Evaluating Mesenchymal Stem-Cell (MSC) Therapy in Non-viral Acute on Chronic Liver Failure (ACLF) Patients - Phase-III Trial

NCT07075315 | Not Yet Recruiting Phase 3

• 1 other identifier: ILBS-ACLF-73
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 3

Brief Summary

Liver disease deaths are rising, but transplants remain scarce in India. With over 100,000 needed annually and only \~2,500 performed, non-transplant options are urgently needed. Regenerative therapy, especially mesenchymal stem cells (MSCs), shows promise but lacks validation, particularly for non-viral ACLF. The proposed NC-CHRM aims to develop and validate MSC-based therapy to promote native liver regeneration and offer a safe, effective, transplant-free treatment.

Conditions

Acute-On-Chronic Liver Failure

Keywords

Acute on chronic Liver Failure; ACLF; Mesenchymal Stem Cell; NC-CHRM

Outcome Measures

Primary Outcomes (1)

• 90-day transplant-free survival

  Day 90

Secondary Outcomes (5)

• 28-day and 6-month transplant free survival

  28-day and 6-month

• Cumulative incidence of acute kidney injury (AKI), sepsis and extrahepatic-extrarenal organ dysfunctions day 28, day 60 and day 90.

  Day 28, day 60 and day 90

• Proportion of patients achieving resolution of ACLF (complete and partial) at day 90.

  Day 90

• Improvement in liver severity indices model for End-stage liver disease (MELD) score by 4 points and improvement in APASL ACLF Research Consortium (AARC) grade by 1 from baseline at 28 days, day 60 and day 90.

  28 days, day 60 and day 90

• Proportion of patients completing treatment without major adverse effects

  5 year

Study Arms (2)

Umbilical cord Mesenchymal stem cell (ucMSC) and standard medical treatment (SMT)

EXPERIMENTAL

Patient randomize for MSC therapy together with standard medical treatment, ucMSC 1 million/kg will be given once a week for 4 week . 250 ml normal saline will be infused 30 minutes prior to ucMSCs infusion. The fresh ucMSCs will then be infused through IV canula peripherally over 30 minutes followed by a further 250 ml normal saline over 20-30 minutes. A baseline early warning score (EWS) will be undertaken with continuous monitoring of pulse and with blood pressure checks every 5 minutes during the cell infusion and then every 15 minutes during the subsequent 2-hour observation period, then every hour for the remaining 10-hour observation period (minimum total of 12 hours observation) after cell infusion. All patients will receive the standard medical treatment (SMT).

Drug: Umbilical cord Mesenchymal stem cell; Other: Standard Medical Treatment

Steroid and Standard medical treatment

ACTIVE COMPARATOR

Patients in steroid group will be given prednisolone 40 mg once daily for 7 days as inpatients. After that Lille score will be calculated on day 7. Responders (Lille score \< 0.45) will be continued on steroids for a total of 4 weeks, followed by 2 weeks of tapering before stopping the therapy. In patients who were nonresponsive to steroids (Lille score \> 0.45) at day 7, steroids will be stopped at day 7 and will receive only SMT. Patients will be managed as per requirement with nutrition, lactulose, intravenous albumin, fluids, blood transfusion or antibiotics as required. Patients with hepatorenal syndrome will be treated with intravenous terlipressin or noradrenaline. Renal replacement therapy will be done for standard indications in patients with severe volume overload, metabolic acidosis, or hyperkalemia unresponsive to goal-directed SMT as described above. Mechanical ventilation and routine intensive care management will be done in patients with multiorgan failure.

Drug: Steroid; Other: Standard Medical Treatment

Interventions

Umbilical cord Mesenchymal stem cell DRUG

ucMSC 1 million/kg will be given once a week for 4 week . 250 ml normal saline will be infused 30 minutes prior to ucMSCs infusion. The fresh ucMSCs will then be infused through IV canula peripherally over 30 minutes followed by a further 250 ml normal saline over 20-30 minutes.

Umbilical cord Mesenchymal stem cell (ucMSC) and standard medical treatment (SMT)

Steroid DRUG

Prednisolone 40 mg once daily for 7 days as inpatients. After that Lille score will be calculated on day 7. Responders (Lille score \< 0.45) will be continued on steroids for a total of 4 weeks, followed by 2 weeks oftapering before stopping the therapy. In patients who were non responsive to steroids (Lille score \> 0.45) at day 7, steroids will be stopped at day 7 and will receive only SMT.

Steroid and Standard medical treatment

Standard Medical Treatment OTHER

All patients will receive the standard medical treatment.

Steroid and Standard medical treatment; Umbilical cord Mesenchymal stem cell (ucMSC) and standard medical treatment (SMT)

Eligibility Criteria

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

You may qualify if:

• ACLF patients with Model for End-Stage Liver Disease (MELD) score \>18 or APASL ACLF Research Consortium (AARC) grade 2 or more with (no or single extrahepatic organ dysfunction or failure having no option of liver transplant.

You may not qualify if:

• Age \<18 or \>65 yrs
• Patients with active sepsis
• Patients with Hepatic Venous Outflow Tract Obstruction(HVOTO) or Extrahepatic Portal Vein Obstruction (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 severe Acute Respiratory Distress Syndrome (ARDS) with Pa02/Fi02 \<150
• Patients with retroviral infections
• Autoimmune hepatitis
• Viral etiology of liver disease
• Co-existent Hepatitis B, Hepatitis C, HIV
• Chronic kidney disease
• Multiorgan failure or Disseminated Intravascular Coagulation
• Pregnancy or active breastfeeding
• Known severe cardiopulmonary diseases (structural or valvular heart disease, coronary artery disease, coronary pulmonary disease, chronic kidney disease)

Sponsors & Collaborators

• Institute of Liver and Biliary Sciences, India: lead
• Indian Council of Medical Research: collaborator

Study Sites (3)

Postgraduate Institute of Medical Education and Research (PGIMER)

Chandigarh, 160012, India

Location

All India Institutes of Medical Sciences (AIIMS)

New Delhi, 110029, India

Location

Institute of Liver & Biliary Sciences

New Delhi, 110070, India

Location

MeSH Terms

Conditions

Acute-On-Chronic Liver Failure

Interventions

Steroids

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Dr. Shiv Kumar Sarin, DM

  Institute of Liver & Biliary Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dr. Anupam Kumar, PhD

CONTACT

01146300000; dr.anupamkumar.ilbs@gmail.com

Fagun Sharma, M.Sc

CONTACT

01146300000; fagun.30sharma@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2025
• First Posted: July 20, 2025
• Study Start (Estimated): January 1, 2028
• Primary Completion (Estimated): December 1, 2031
• Study Completion (Estimated): December 1, 2031
• Last Updated: August 17, 2025

Record last verified: 2025-08

Locations

IN (3)