Mesenchymal Stem Cell Transplantation for Acute-on-chronic Liver Failure

• ClinicalTrials.gov Identifier: NCT03668171
• Recruitment Status: Unknown
• First Posted: September 12, 2018
• Last Update Posted: September 12, 2018
• Sponsor: Xijing Hospital of Digestive Diseases
• Information provided by (Responsible Party): Han Ying, Xijing Hospital of Digestive Diseases

Tracking Information

• First Submitted Date: September 10, 2018
• First Posted Date: September 12, 2018
• Last Update Posted Date: September 12, 2018
• Actual Study Start Date: December 10, 2017
• Estimated Primary Completion Date: December 31, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 10, 2018)

Efficacy: 12 week mortality rate [ Time Frame: 12 weeks ]

mortality rate assessed at week 12

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: September 10, 2018)

Clinical remission rate at week 12 [ Time Frame: 12 weeks ]

Clinical remission define as: significant improvement of symptoms and resolution of hepatoencephalopathy; TBIL decrease to below 5 times of ULN，PTA>40% or INR<1.6

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Mesenchymal Stem Cell Transplantation for Acute-on-chronic Liver Failure
• Official Title: Mesenchymal Stem Cell Transplantation for Acute-on-chronic Liver Failure, a Randomized, Double Blind, Placebo Controlled Trial
• Brief Summary: Mesenchymal stem cells (MSC) has been reported to improved outcomes of acute-on-chronic liver failure(ACLF). More randomization controlled studies are needed to confirm the effect of MSC treatment for ACLF. This study aimed to investigate the efficacy of mesenchymal stem cells in ACLF patients. This study is an double-blind multicenter randomized and placebo-controlled study. Patients with with ACLF will be randomly assigned to receive MSC treatment (experimental) or standard medical treatment (control). Three times of MSC infusion (0.1-1x10E6cells/kg body weight) via peripheral vein will be given to the experimental group (once per week). The primary outcome is 12 week mortality. Secondary outcomes are clinical remission rate and changes of liver function indices and liver function scores.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

Randomization will be blinded to participant, care provider, investigator and outcome assessors.

Primary Purpose: Treatment

• Condition: Acute-On-Chronic Liver Failure

Intervention

Procedure: mesenchymal stem cell transplantation or placebo infusion via peripheral vein

0.1-1x10E6 MSCs/kg body weight will be administered via peripheral vein for 3 times at week 0, 4 and 8 mesenchymal stem cell mesenchymal stem cell infusion produced by Cell products of National Engineering Research Center(short for CPNERC), Tianjin, China For control group, placebo infusions will be given to the participants at the same time points

Study Arms

• Experimental: MSC group
  mesenchymal stem cell transplantation via peripheral vein: 0.1-1x10E6 MSCs/kg body weight administered via peripheral vein at week 0, 1, 2 weeks
  Intervention: Procedure: mesenchymal stem cell transplantation or placebo infusion via peripheral vein
• Placebo Comparator: control
  placebo infusions (placebo infusion differs from the experimental infusion in only that placebo has no mesenchymal stem cells) will be administered via peripheral vein at week 0, 1, 2
  Intervention: Procedure: mesenchymal stem cell transplantation or placebo infusion via peripheral vein

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: September 10, 2018): 200
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2020
• Estimated Primary Completion Date: December 31, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Age between 18-70 years old
• Meeting the criteria of ACLF defined as: 1. definitive chronic liver diseases, acute decompensation within 4 weeks; 2. Significant GI symptom as such fatigue, jaundice,; 3. total bilirubin (TBIL) ≥170 µmo1/L or daily increase of TBIL ≥17.1 µmo1/L; 4. PTA≤40% or INR≥ 1.5; 5. Decompensation of liver functions such as ascites or hepatoencephalopathy;
• MELD score between 17-30. (MELD(i) = 0.957 × ln(Cr) + 0.378 × ln(bilirubin) + 1.120 × ln(INR) + 0.643)
• Chronic liver disease with definitive etiology such as viral hepatitis, alcohol liver disease, drug induced liver injury or autoimmune liver diseases
• Informed consent

Exclusion Criteria:

• Sever complications with 30 days ( GI bleeding, severe infection)；

  --liver cancer or other malignancies

• patients on liver transplantation list
• patients with uncontrolled infections
• severe renal failure
• Severe chronic obstructive pulmonary disease COPD (GOLD III-IV)
• Extrahepatic cholanstasis patients due to biliary obstruction.
• HIV infection
• Pregnant or breast-feeding females.
• Enrolled in other clinical trials with 3 months
• other conditions considered inappropriate for the study

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT03668171
• Other Study ID Numbers: KY20172049-1
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Study protocol, statistical analysis processes and clinical data of individual participants will be shared.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Analytic Code
• Time Frame: within 12 months after the study completion and before publications of the findings.

• Responsible Party: Han Ying, Xijing Hospital of Digestive Diseases
• Study Sponsor: Xijing Hospital of Digestive Diseases
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Xijing Hospital of Digestive Diseases
• Verification Date: September 2018