Precise Profiling of Liver Disease Patients With DPMAS Therapy, Treating Optimal Patients and Achieving Hard Endpoint (PADSTONE Study) (PADSTONE)

Precise Profiling of Liver Disease Patients With DPMAS Therapy, Treating Optimal Patients and Achieving Hard Endpoint: a Multicenter, Cluster-controlled Study (PADSTONE Study)

Acute-on-chronic liver failure (ACLF) is life-threaten syndrome in patients with chronic liver disease. In China, hepatitis B virus (HBV) is the main etiology of cirrhosis and HBV-ACLF is characterized by multiple organs failure (liver, coagulation and kidney, etc.) and associated with high risk of short-tern death. For the treatment of ACLF patients, recent studies investigated the efficiency of extracorporeal liver support, such as albumin dialysis, plasma exchange. However, the efficiencies remain unclear. Liver transplantation is the most efficient way to improve the survival of ACLF patients, especially for those patients with three or more organ failure.

More recently，an extracorporeal system which is called double plasma molecular absorption system (DPMAS) was applied for the treatment of ACLF patients. DPMAS is an extracorporeal procedure that combines two hemoperfusion machines. During the procedure, toxic plasma is separated and cleansed by perfusion over two absorbers, and the final cleansed plasma is then returned to patients. It does not require large volumes of plasma and nor does it bear the risk of plasma-associated allergic reaction or disease transmissions. PMAS can attenuate the jaundice in a short term and decrease the bilirubin concentration, which then reduces the toxicities of bile acid and high levels of bilirubin on the hepatocytes. Although DPMAS treatment is applied in the clinical practice for those patients with liver failure, it still lack of compelling evidence in terms of real efficiency.

Thus, in this prospective, multicenter and cluster-controlled study, the investigators aim to identify the optimal liver disease patients by using hard endpoints (short-term mortality and disease progression). Moreover, this study will collect biological samples, including plasma, urine and stool, to explore the precise profiling of ACLF patients with DPMAS therapy by multi-omics detection.

Study Overview

• Status: Recruiting
• Conditions: DPMAS Therapy in Liver Disease Patients
• Intervention / Treatment: Other: Double plasma molecular absorption system

• Study Type: Observational
• Enrollment (Estimated): 1300

Contacts and Locations

• Study Contact: Name: Jinjun Chen, Doctor; Phone Number: 18588531001; Email: chjj@smu.edu.cn
• Study Contact Backup: Name: Beiling Li; Phone Number: 13570541527; Email: 820584791@qq.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Recruiting
      • Nanfang Hospital
      • Contact: Jinjun Chen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Cohort 1:

Liver failure patients (Total bilirubin ≥ 12mg/dl and INR ≥ 1.5) treat with DPMAS alone or in combination with plasma exchange

Cohort 2:

Liver failure patients (Total bilirubin ≥ 12mg/dl and INR ≥ 1.5) with standard medical therapy except for DPMAS treatment or other artificial liver support system

Description

Inclusion Criteria:

1. Hospitalized patients
2. Age >18 years
3. Chronic liver disease regardless of the etiology
4. Total bilirubin ≥ 12mg/dl and INR ≥ 1.5

Exclusion Criteria:

1. with more than three organ failures (SOFA criteria);
2. the pregnant;
3. with severe non-hepatic disease (such as chronic obstructive pulmonary disease level IV, chronic kidney disease with end-stage renal failure, myocardial infarction within 3 months before admission); 4) human immunodeficiency virus (HIV) infection without treatment;

5) patients with unstable hemodynamics caused by infection or acute bleeding; 6) hospital stays <48 hours; 7) diagnosis of hepatocellular carcinoma during screening period; 8) for the DPMAS clusters: patients unwilling to receive DPMAS treatment alone or in combination with PE; 9) for the SMT clusters: patients plan to receive DPMAS therapy or other ALSS; 10) not suitable to participate in this study judging by researchers; 11) not sign the informed consent.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Double plasma molecular absorption system treatment; Patients treat with DPMAS alone or in combination with plasma exchange	Other: Double plasma molecular absorption system; DPMAS is an extracorporeal procedure that combines two hemoperfusion machines. During the procedure, toxic plasma is separated and cleansed by perfusion over two absorbers, and the final cleansed plasma is then returned to patients. It does not require large volumes of plasma and nor does it bear the risk of plasma-associated allergic reaction or disease transmissions. DPMAS can attenuate the jaundice in a short term and decrease the bilirubin concentration, which then reduces the toxicities of bile acid and high levels of bilirubin on the hepatocytes; Other Names: DPMAS treatment
Standard medical therapy; Patients with standard medical therapy except for DPMAS treatment or other artificial liver support system

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The rate of progression with 4 weeks	The progression of ACLF with 4 weeks	4 weeks
The 4-week transplant-free mortality	The 4-week transplant-free mortality	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The transplant-free mortality within 12 weeks	The transplant-free mortality within 12 weeks	12 weeks
The improvement of ACLF with 12 weeks	The improvement of ACLF with 12 weeks	12 weeks

Collaborators and Investigators

• Sponsor: Nanfang Hospital, Southern Medical University
• Collaborators: The First Affiliated Hospital of Anhui Medical University; The First Affiliated Hospital of Nanchang University; Xiangya Hospital of Central South University; LanZhou University; Peking University People's Hospital; Beijing YouAn Hospital; Beijing Ditan Hospital; Beijing 302 Hospital; The Second Hospital of Hebei Medical University; Huashan Hospital; Southwest Hospital, China; West China Hospital; Qilu Hospital of Shandong University; First Affiliated Hospital of Fujian Medical University; First Affiliated Hospital Xi'an Jiaotong University; The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School; Ruijin Hospital; First Affiliated Hospital of Zhejiang University; Shandong Provincial Hospital; The First Affiliated Hospital of Zhengzhou University; The First Hospital of Jilin University; Henan Provincial People's Hospital; Hunan Provincial People's Hospital; Shanghai Public Health Clinical Center; Wuhan Union Hospital, China; First People's Hospital of Foshan; The Second Affiliated Hospital of Chongqing Medical University; The Affiliated Hospital Of Guizhou Medical University; General Hospital of Ningxia Medical University; The Second Hospital of Shandong University; Tianjin Third Central Hospital; The First Affiliated Hospital of Shanxi Medical University; Second Xiangya Hospital of Central South University; Second Affiliated Hospital of Guangzhou Medical University; First Affiliated Hospital of Xinjiang Medical University; Hebei Medical University Third Hospital; Sichuan Provincial People's Hospital; Second Affiliated Hospital of Nanchang University; The Affiliated Hospital of Xuzhou Medical University; Shanghai Jiao Tong University Affiliated Sixth People's Hospital; Taihe Hospital; People's Hospital of Guangxi; The Second Affiliated Hospital of Kunming Medical University; Hainan People's Hospital; First Affiliated Hospital of Guangxi Medical University; Meng Chao Hepatobiliary Hospital of Fujian Medical University; The Ninth Hospital of Nanchang; People's Hospital of Anshun City of Guizhou Province; The First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine; The First Affiliated Hospital of Shandong First Medical University; Shanghai Public Health Clinical Center of Fudan University; The First Hospital of Yunnan Province; Chengdu Public Health Clinical Center; Shandong Provincial Clinical Center for Public Health; Union Hospital, Tongji Medical College; Zhengzhou University Affiliated Luoyang Centre Hospital; The Affiliated Hospital of Zunyi Medical University; Beijing Luhe Hospital of Capital Medical University
• Investigators: Study Director: Jinjun Chen, Doctor, Nanfang Hospital, Sourthern Medical University

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2021
• Primary Completion (Estimated): December 30, 2023
• Study Completion (Estimated): December 30, 2024

Study Registration Dates

• First Submitted: October 31, 2021
• First Submitted That Met QC Criteria: November 11, 2021
• First Posted (Actual): November 22, 2021

Study Record Updates

• Last Update Posted (Actual): September 18, 2023
• Last Update Submitted That Met QC Criteria: September 14, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: mortality; liver disease; double plasma molecular absorption system; acute-on-chronic liver failure
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases
• Other Study ID Numbers: NFEC-2021-259

Drug and device information, study documents

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