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

N/AActive Not RecruitingNCT05129904

Nanfang Hospital, Southern Medical University1,300 enrolled

Overview

Acute-on-chronic liver failure (ACLF) is a life-threatening syndrome occurring in patients with chronic liver disease. In China, hepatitis B virus (HBV) is the main cause of cirrhosis. HBV related ACLF is characterized by multiple organs failure (liver, coagulation and kidney, etc.) and confers with high risk of short-term mortality. For the treatment of ACLF patients, recent studies have explored the therapeutic efficacy of extracorporeal liver support therapies, such as albumin dialysis, plasma exchange. However, the clinical efficacy remains to be fully elucidated. Liver transplantation is the most efficient way to improve the survival of ACLF patients, especially for those suffering from three or more organ failures. Recently, a novel extracorporeal system which is called double plasma molecular adsorption system (DPMAS) has been applied for the treatment of ACLF patients. DPMAS is an extracorporeal therapeutic procedure that combines two hemoperfusion devices. During treatment, toxic plasma is isolated and purified via perfusion through two adsorbers, after which the purified plasma is reinfused back into the patient's circulation. This technique requires no massive plasma supply and avoids the risks of plasma-related allergic reactions and pathogen transmission. DPMAS can rapidly alleviate jaundice and lower serum bilirubin levels, thereby mitigating the hepatotoxic effects induced by excessive bilirubin and bile acids. Despite the widespread clinical application of DPMAS in patients with liver failure, high-quality evidence supporting its definite clinical efficacy remains insufficient. Accordingly, this prospective, multicenter cluster-controlled study is designed to evaluate the clinical benefits of DPMAS via validated hard clinical endpoints, including short-term mortality and disease progression, and screen out suitable candidate patients. Furthermore, biological specimens including plasma, urine and feces will be collected to characterize the molecular profiles of ACLF patients receiving DPMAS treatment through multi-omics analyses.

Study Type

OBSERVATIONAL

Enrollment

1,300

Conditions

DPMAS Therapy in Liver Disease Patients

Interventions

Double plasma molecular absorption systemOTHER

As a type of ECLS, double plasma molecular adsorption system (DPMAS) integrates plasma filtration with two specific adsorption membranes, which can efficiently remove bilirubin and the middle-molecular toxins, respectively. In the DPMAS clusters, patients receive at least one DPMAS treatment session during the study period, as treatment details regarding the number of DPMAS sessions and session intervals are made upon institutional protocols. DPMAS treatment can be applied either alone or in combination with PE, and both modalities are permitted in this study. PE is allowed in both groups as standard supportive care.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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 ≥ 3 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 decline to receive DPMAS treatment alone or in combination with PE; 9. For the SOC clusters: patients plan to receive DPMAS therapy; 10. Not suitable to participate in this study judging by researchers (e.g., patients with severe advanced pancreatic tumors, hematological tumors); 11. Not sign the informed consent.

Locations (56)

The Second Affiliated Hospital of Chongqing Medical University

Chongqing, Chongqing Municipality, China

Nanfang Hospital

Guangzhou, Guangdong, China

The Third Hospital of Hebei Medical University

Hebei, Hebei, China

Hunan Provincial People's Hospital

Changsha, Hunan, China

Xiangya Hospital of Central South University

Changsha, Hunan, China

Outcomes

Primary Outcomes

The rate of progression within 4 weeks

The progression of ACLF within 4 weeks

Time frame: 4 weeks

The 4-week transplant-free mortality

Time frame: 4 weeks

Secondary Outcomes

The transplant-free mortality within 12 weeks

Time frame: 12 weeks

The progression of ACLF within 12 weeks

The progression rate of ACLF within 12 weeks

Time frame: 12 weeks