Acute-On-Chronic Liver FailurePhase 3NC-CHRMNCT07075315
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
A Phase 3 study testing Umbilical cord Mesenchymal stem cell, Steroid and Standard Medical Treatment in people with Acute-On-Chronic Liver Failure, run by Institute of Liver and Biliary Sciences, India at 3 sites in India.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Acute-On-Chronic Liver Failure
- What is being tested?
- Umbilical cord Mesenchymal stem cell, Steroid and Standard Medical Treatment
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 3 sitesIndia
- Study dates
- Jan 2028to Dec 2031
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 16Show fewer
- 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)
- Lack of informed consent
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
India3 sites
Postgraduate Institute of Medical Education and Research (PGIMER)
Chandigarh, 160012
Sunil Taneja, DM
All India Institutes of Medical Sciences (AIIMS)
New Delhi, 110029
Shalimar, DM
Institute of Liver & Biliary Sciences
New Delhi, 110070
Dr. Anupam Kumar, PhD, 01146300000, dr.anupamkumar.ilbs@gmail.com
Fagun Sharma, M.Sc, 01146300000, fagun.30sharma@gmail.com
About this study
Official title: National Collaborative Centre for Hepatic Regenerative Medicine (NC-CHRM): To Study the Safety and Efficacy of Mesenchymal Stem-Cell Therapy in the Management of Non-viral ACLF Patients: Phase-III Clinical Study
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.
Read the detailed description
The incidence of deaths from chronic liver diseases (CLD) and cirrhosis are rapidly increasing globally, including India. Liver transplant is the only curative option. Unfortunately, transplant is often not feasible. There is a need for nearly 100,000 liver transplants every year in India, though, only about 2,500 transplants are being done at present across the country. There is therefore, a huge unmet need of developing non-transplant options for chronic liver disease patients. In this regard emerging science of regenerative therapy holds great promises but therapeutic benefit of these therapies is limited due to lack of clinical validation.
Liver failure is failure of regeneration hence, potentiating native liver repair and regeneration can serve as potential non-transplant approaches. Others and us have shown in experimental studies that mesenchymal stem cells (MSCs) can improve hepatic regeneration. MSC therapy trials in decompensated cirrhosis and viral Acute-on-Chronic Liver Failure (ACLF) in Korea, China and Japan have shown promise but their utility in non-viral ACLF is limited. In the proposed National Collaborative Centre for Hepatic Regenerative Medicine (NC-CHRM) we will use this novel regenerative medicine approaches MSC for management of acute liver failure in non-viral ACLF to develop safe and effective regenerative therapy clinical protocol for transplant free management of liver failure in cirrhosis. Using integrated cellular, molecular and functional analysis we will also establish their mechanism of action and identify biomarker to access therapeutic response.
- Conditions
- Acute-On-Chronic Liver Failure
- Being tested
- Umbilical cord Mesenchymal stem cell, Steroid, Standard Medical Treatment
- Keywords
- Acute on chronic Liver Failure, ACLF, Mesenchymal Stem Cell, NC-CHRM
- Medical subject headings
- Acute-On-Chronic Liver Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Umbilical cord Mesenchymal stem cellDrug
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.
SteroidDrug
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.
Standard Medical TreatmentOther
All patients will receive the standard medical treatment.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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. Receives: Drug: Steroid; Other: Standard Medical Treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
90-day transplant-free survival
Measured: Day 90
Secondary outcomes (5)
28-day and 6-month transplant free survival
Measured: 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.
Measured: Day 28, day 60 and day 90
Proportion of patients achieving resolution of ACLF (complete and partial) at day 90.
Measured: 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.
Measured: 28 days, day 60 and day 90
Proportion of patients completing treatment without major adverse effects
Measured: 5 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jul 2025
- Study startJan 2028 (estimated)
- Primary completionDec 2031 (estimated)
- Study completionDec 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute-On-Chronic Liver FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Institute of Liver and Biliary Sciences, India
- Sponsor type
- University, hospital or other
- Collaborators
- Indian Council of Medical Research
- Responsible party
- Sponsor
- Investigators
- Dr. Shiv Kumar Sarin, DM, Principal investigator, Institute of Liver & Biliary Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07075315
- Sponsor's protocol ID
- ILBS-ACLF-73
- Acronym
- NC-CHRM
- Status last verified
- Aug 2025
- First submitted
- 11 Jul 2025
- Last updated
- 17 Aug 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- National Collaborative Centre for Hepatic Regenerative Medicine (NC-CHRM): To Study the Safety and Efficacy of Mesenchymal Stem-Cell Therapy in the Management of Non-viral ACLF Patients: Phase-III Clinical Study
- ClinicalTrials.gov ID
- NCT07075315
- Acronym / sponsor ID
- NC-CHRM / ILBS-ACLF-73
- Conditions
- Acute-On-Chronic Liver Failure
- Keywords
- Acute on chronic Liver Failure, ACLF, Mesenchymal Stem Cell, NC-CHRM
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Institute of Liver and Biliary Sciences, IndiaUniversity, hospital or other
- Collaborators
- Indian Council of Medical Research
- Study start
- Jan 2028 (estimated)
- Primary completion
- Dec 2031 (estimated)
- Study completion
- Dec 2031 (estimated)
- First posted
- 20 Jul 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The incidence of deaths from chronic liver diseases (CLD) and cirrhosis are rapidly increasing globally, including India. Liver transplant is the only curative option. Unfortunately, transplant is often not feasible. There is a need for nearly 100,000 liver transplants every year in India, though, only about 2,500 transplants are being done at present across the country. There is therefore, a huge unmet need of developing non-transplant options for chronic liver disease patients. In this regard emerging science of regenerative therapy holds great promises but therapeutic benefit of these therapies is limited due to lack of clinical validation.
Liver failure is failure of regeneration hence, potentiating native liver repair and regeneration can serve as potential non-transplant approaches. Others and us have shown in experimental studies that mesenchymal stem cells (MSCs) can improve hepatic regeneration. MSC therapy trials in decompensated cirrhosis and viral Acute-on-Chronic Liver Failure (ACLF) in Korea, China and Japan have shown promise but their utility in non-viral ACLF is limited. In the proposed National Collaborative Centre for Hepatic Regenerative Medicine (NC-CHRM) we will use this novel regenerative medicine approaches MSC for management of acute liver failure in non-viral ACLF to develop safe and effective regenerative therapy clinical protocol for transplant free management of liver failure in cirrhosis. Using integrated cellular, molecular and functional analysis we will also establish their mechanism of action and identify biomarker to access therapeutic response.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Umbilical cord Mesenchymal stem cell (ucMSC) and standard medical treatment (SMT) | Experimental | Drug: Umbilical cord Mesenchymal stem cell, Other: Standard Medical TreatmentPatient 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). |
| Steroid and Standard medical treatment | Active comparator | Drug: Steroid, Other: Standard Medical TreatmentPatients 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (16 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Umbilical cord Mesenchymal stem cellucMSC 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. | Drug | Umbilical cord Mesenchymal stem cell (ucMSC) and standard medical treatment (SMT) |
| SteroidPrednisolone 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. | Drug | Steroid and Standard medical treatment |
| Standard Medical TreatmentAll patients will receive the standard medical treatment. | Other | Steroid and Standard medical treatment, Umbilical cord Mesenchymal stem cell (ucMSC) and standard medical treatment (SMT) |
Primary outcome
90-day transplant-free survival
Time frame: Day 90
5 secondary outcomes
28-day and 6-month transplant free survival
Time frame: 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.
Time frame: Day 28, day 60 and day 90
Proportion of patients achieving resolution of ACLF (complete and partial) at day 90.
Time frame: 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.
Time frame: 28 days, day 60 and day 90
Proportion of patients completing treatment without major adverse effects
Time frame: 5 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2025.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Dr. Shiv Kumar Sarin, DM principal investigator
Institute of Liver & Biliary Sciences
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Umbilical cord Mesenchymal stem cell, Steroid and Standard Medical Treatment in people with Acute-On-Chronic Liver Failure, run by Institute of Liver and Biliary Sciences, India at 3 sites in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 17 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Dr. Anupam Kumar, PhD (01146300000, dr.anupamkumar.ilbs@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
90-day transplant-free survival (time frame: Day 90). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Aug 2025.