Clinical trial NCT05129904: Precise Profiling of Liver Disease Patients With DPMAS Therapy, Treating Optimal Patients and Achieving Hard Endpoint (PADSTONE Study)
Official title: Precise Profiling of Liver Disease Patients With DPMAS Therapy, Treating Optimal Patients and Achieving Hard Endpoint: a Multicenter, Cluster-controlled Study (PADSTONE Study)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: DPMAS Therapy in Liver Disease Patients
Keywords: double plasma molecular absorption system
liver disease
acute-on-chronic liver failure
mortality
Lead sponsor: Nanfang Hospital, Southern Medical University
Sponsor class: OTHER
Collaborators: name: Xiangya Hospital of Central South University
name: The First Affiliated Hospital of Nanchang University
name: Tianjin Third Central Hospital
name: Henan Provincial People's Hospital
name: The First Affiliated Hospital of Zhengzhou University
name: Beijing YouAn Hospital
name: The First Affiliated Hospital of Anhui Medical University
name: West China Hospital
name: The Second Affiliated Hospital of Kunming Medical University
name: Meng Chao Hepatobiliary Hospital of Fujian Medical University
name: The Second Affiliated Hospital of Chongqing Medical University
name: First Affiliated Hospital of Zhejiang University
name: The Ninth Hospital of Nanchang
name: First Affiliated Hospital of Xinjiang Medical University
name: The First Affiliated Hospital of Shanxi Medical University
name: Taihe Hospital
name: Beijing 302 Hospital
name: Shanghai Public Health Clinical Center of Fudan University
name: First Affiliated Hospital Xi'an Jiaotong University
name: Southwest Hospital, China
name: Wuhan Union Hospital, China
name: Qilu Hospital of Shandong University
name: Beijing Ditan Hospital
name: First Affiliated Hospital of Guangxi Medical University
name: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
name: Shanghai Public Health Clinical Center
name: Shandong Provincial Hospital
name: The First Hospital of Jilin University
name: Sichuan Provincial People's Hospital
name: Huashan Hospital
name: People's Hospital of Anshun City of Guizhou Province
name: LanZhou University
name: General Hospital of Ningxia Medical University
name: Second Xiangya Hospital of Central South University
name: The First Hospital of Yunnan Province
name: Chengdu Public Health Clinical Center
name: Ruijin Hospital
name: Shanghai Jiao Tong University Affiliated Sixth People's Hospital
name: Shandong Provincial Clinical Center for Public Health
name: Shandong First Medical University
name: The Second Hospital of Shandong University
name: Second Affiliated Hospital of Nanchang University
name: The Affiliated Hospital of Xuzhou Medical University
name: Hunan Provincial People's Hospital
name: Union Hospital, Tongji Medical College
name: Zhengzhou University Affiliated Luoyang Centre Hospital
name: Hebei Medical University Third Hospital
name: The Second Hospital of Hebei Medical University
name: Hainan People's Hospital
name: Zunyi Medical College
name: The Affiliated Hospital Of Guizhou Medical University
name: Second Affiliated Hospital of Guangzhou Medical University
name: The First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine
name: People's Hospital of Guangxi Zhuang Autonomous Region
name: First People's Hospital of Foshan
name: First Affiliated Hospital of Fujian Medical University
name: Capital Medical University
name: Peking University People's Hospital
First posted: 2021-11-22
Enrollment: 1300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: The rate of progression with 4 weeks
timeFrame: 4 weeks
measure: The 4-week transplant-free mortality
timeFrame: 4 weeks
Secondary outcomes:
measure: The transplant-free mortality within 12 weeks
timeFrame: 12 weeks
measure: The improvement of ACLF with 12 weeks
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Nanfang Hospital
state: Guangdong
Study officials:
affiliation: Nanfang Hospital, Sourthern Medical University
name: Jinjun Chen, Doctor
role: STUDY_DIRECTOR
References: