Study on MAFLD-related Cirrhosis Prevention and Treatment Strategies (SMART)

Prospective Cohort Study on MAFLD-related Cirrhosis Prevention and Treatment Strategies

To establish a prospective, multicenter, biopsie-confirmed clinical cohort of MAFLD-related cirrhosis (F3-F4) in China, and analyze the clinical, histopathological features and natural outcomes of MAFLD-associated liver fibrosis/cirrhosis in China. And than to conducted a real-world study of different strategies of Chinese characteristics for the prevention and treatment of MAFLD-related cirrhosis to evaluate the efficacy and safety of the strategies.

Study Overview

• Status: Not yet recruiting
• Conditions: Cirrhosis; Metabolic Dysfunction-associated Fatty Liver Disease
• Intervention / Treatment: Drug: Pioglitazone metformin tablets; Drug: Other drugs; Other: Drug-free

• Study Type: Interventional
• Enrollment (Estimated): 1000
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Junping Shi, Doctor; Phone Number: 15869151180; Email: 20181580@hznu.edu.cn
• Study Contact Backup: Name: Jing Liu; Phone Number: 15869151180; Email: 20181580@hznu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18-75 years old, gender and ethnicity are not limited;
2. Meet the diagnostic criteria for MAFLD;
3. F0-F4 stage of liver fibrosis confirmed by liver biopsy within 24 weeks;
4. Be willing to sign informed consent.

Exclusion Criteria:

1. Cirrhosis due to any chronic liver disease other than MAFLD (including but not limited to alcohol or drug abuse, medications, chronic hepatitis B or C, autoimmune, hemochromatosis, Wilson's disease, alpha1-antitrypsin deficiency);
2. Any clinical evidence or history of peritonitis, varicose bleeding, or spontaneous encephalopathy;
3. According to the investigators' assessment, a history of heavy drinking for more than 3 months continuously within the previous year was selected. (Note: Heavy drinking was defined as more than 20 g per day on average for female subjects and more than 30 g per day for male subjects).
4. Use of NAFLD-related medication history (amiodarone, methotrexate, systemic glucocorticoids, tetracycline, tamoxifen, larger than hormone replacement doses of estrogen, anabolic steroids, valproic acid, and other known hepatotoxins) for more than 2 weeks within the year prior to screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pioglitazone metformin tablets; Pioglitazone metformin tablets 15mg/500mg (To control the fasting blood glucose below 7.0mmol/l, adjust the dose and dosage according to the blood glucose)	Drug: Pioglitazone metformin tablets; Drug intervention for 24 weeks and follow-up for another 72 weeks (fasting blood glucose was controlled below 7.0mmol/l throughout the study)
Active Comparator: Other drug; Chinese patent medicine or Hypoglycemic drugs other than pioglitazone metformin tablets, pioglitazone, metformin and GLP1 ((To control the fasting blood glucose below 7.0mmol/l)	Drug: Other drugs; Chinese patent medicine or hypoglycemic drugs other than pioglitazone metformin tablets, pioglitazone, metformin, GLP1
Other: Drug-free	Other: Drug-free; Drug-free

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Controlled attenuation parameter (CAP)		Through study completion, an average of 96 week.
Transient elastography		Through study completion, an average of 96 week.
Model for end-stage liver disease score	Model for end-stage liver disease score ranges from 6 to 40 score (>40 calculated as 40 scores)，higher scores mean a worse outcome	Through study completion, an average of 96 week.
Portalvein pressure gradient(HVPG)		Through study completion, an average of 96 week.
Prevalence of cirrhosis		Through study completion, an average of 96 week.
Prevalence of liver transplantation		Through study completion, an average of 96 week.
Prevalence of decompensated cirrhosis		Through study completion, an average of 96 week.

Collaborators and Investigators

• Sponsor: The Affiliated Hospital of Hangzhou Normal University

Study record dates

Study Major Dates

• Study Start (Estimated): November 18, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: November 5, 2023
• First Submitted That Met QC Criteria: November 15, 2023
• First Posted (Estimated): November 16, 2023

Study Record Updates

• Last Update Posted (Estimated): November 16, 2023
• Last Update Submitted That Met QC Criteria: November 15, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Treatment Strategies; Multicenter Real-World Study
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Fatty Liver; Liver Cirrhosis; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin; Pioglitazone
• Other Study ID Numbers: SMART

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No