The Treatment of Hepatocirrhosis and Portal Hypertension

Partial Splenic Embolization Combined with Endoscopic Therapies and NSBB Decreases the Variceal Rebleeding Rate and Increases Recompensation Rate in Cirrhosis Patients with Hypersplenism: a Multicenter Randomized Controlled Trial

This study compare the efficiency of partial splenic embolization +endoscopical therapy with endoscopical therapy alone in gastroesophageal variceal haemorrhage accompanied with splenomegaly or hypersplenism of hepatocirrhosis and portal hypertension treatment.

Study Overview

• Status: Completed
• Conditions: Portal Hypertension; Hepatic Cirrhosis
• Intervention / Treatment: Procedure: Endoscopic therapy+ beta blockers; Procedure: Endoscopic therapy+ PSE+beta blockers; Procedure: beta blockers; Procedure: Endoscopic therapy; Procedure: Endoscopic therapy+ PSE; Procedure: Somatostatin+Endoscopic therapy; Procedure: Somatostatin+Endoscopic therapy+PSE

Detailed Description

Endoscopic therapy is the mature treatment of gastroesophageal variceal haemorrhage and PSE is an effective method for treatment of the hypersplenism and portal hypertension. Existing researches show that endoscopic therapy + PSE is more effective than endoscopic therapy alone in prevention of esophageal varices bleeding recurrence in the patients with liver cirrhosis. However, there is few articles which proved long-term effectiveness of endoscopic therapy + PSE, it needs further research on this issue. This study compares the efficiency of partial splenic embolization +endoscopic therapy with endoscopic therapy alone in the treatment of gastroesophageal variceal haemorrhage accompanied with splenomegaly or hypersplenism in the patients with hepatocirrhosis and portal hypertension.

• Study Type: Interventional
• Enrollment (Actual): 108
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China, 250012
      • Department of Gastroenterology,Qilu Hospital,Shandong University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients aged between 18 and 75 years
• Patients who had recovered from an episode of VH or patients who had survived from acute VH and there was no bleeding for consecutive 5 days
• Patients with a diagnosis of liver cirrhosis and portal hypertension on clinical examination, laboratory test, and imaging or histological examination
• Patients with hypersplenism and thrombocytopenia (platelets < 100,000/µL).

Exclusion criteria :

• Previous therapy (splenectomy, PSE, EVL, tissue adhesive injection, or usage of (NSBB) to prevent rebleeding
• Bleeding from isolated gastric or ectopic varices
• Hepatocellular carcinoma or other malignant tumors
• Contraindications for the use of NSBBs, hepatic failure, and Child-Pugh class C with large amount ascites, or grade 3-5 hepatic encephalopathy, or prothrombin activity ≤ 40%
• Hepatic failure
• Contraindications for PSE
• Pregnancy and lactation
• Inability to sign the informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Secondary prevention-1; Endoscopic therapy+ beta blockers	Procedure: Endoscopic therapy+ beta blockers; Endoscopic variceal ligation (EVL) is for the secondary prophylaxis of esophageal variceal hemorrhage,and Cyanoacrylate injection is for gastric varices (GV).A standard dose of NSBB (propranolol) was applied to patients according to the Baveno VI recommendations if there were no contraindications.
Experimental: Secondary prevention-2; Endoscopic therapy+ PSE+beta blockers	Procedure: Endoscopic therapy+ PSE+beta blockers; Endoscopic variceal ligation (EVL) is for the secondary prophylaxis of esophageal variceal hemorrhage,and Cyanoacrylate injection is for gastric varices (GV).A standard dose of NSBB (propranolol) was applied to patients according to the Baveno VI recommendations if there were no contraindications.Partial splenic embolization (PSE) is one of the intra-arterial therapeutic approaches to embolize 60-80% splenic blood flow.
Experimental: Primary prevention-1; Beta blockers	Procedure: beta blockers; A standard dose of NSBB (propranolol) was applied to the primary prevention patients according to the Baveno VI recommendations if there were no contraindications.
Experimental: Primary prevention-2; Endoscopic therapy	Procedure: Endoscopic therapy; Endoscopic variceal ligation (EVL) is for the primary prophylaxis of esophageal variceal hemorrhage,and Cyanoacrylate injection is for gastric varices (GV).
Experimental: Primary prevention-3; Endoscopic therapy+ PSE	Procedure: Endoscopic therapy+ PSE; Endoscopic variceal ligation (EVL) is for the primary prophylaxis of esophageal variceal hemorrhage,and Cyanoacrylate injection is for gastric varices (GV).Partial splenic embolization (PSE) is one of the intra-arterial therapeutic approaches to embolize 60-80% splenic blood flow.
Experimental: Acute bleeding-1; Somatostatin+endoscopic therapy	Procedure: Somatostatin+Endoscopic therapy; The first dose of 250 was injected intravenously, followed by a continuous iv infusion of 250 for 3-5 days. Endoscopic variceal ligation (EVL) is for the acute bleeding of esophageal variceal hemorrhage,and Cyanoacrylate injection is for gastric varices (GV).
Experimental: Acute bleeding-2; Somatostatin+endoscopic therapy+PSE	Procedure: Somatostatin+Endoscopic therapy+PSE; The first dose of 250 was injected intravenously, followed by a continuous iv infusion of 250 for 3-5 days. Endoscopic variceal ligation (EVL) is for the acute bleeding of esophageal variceal hemorrhage,and Cyanoacrylate injection is for gastric varices (GV).Partial splenic embolization (PSE) is one of the intra-arterial therapeutic approaches to embolize 60-80% splenic blood flow.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary endpoint was variceal rebleeding	The rebleeding rate of the varices in the EP group will compared to that in the E group during the follow up.	2 years
The primary outcome was the hepatic recompensation rate based on Baveno VII criteria after 1-year follow-up.	The hepatic recompensation rate based on Baveno VII criteria in the EP group will compared to that in the E group during the follow-up. Hepatic recompensation is a comprehensive assessment index defined as meeting all of the following criteria simultaneously: (1)Etiological Control: Removal/suppression/cure of the primary cause of cirrhosis (e.g., hepatitis C virus elimination, sustained suppression of hepatitis B virus, and sustained abstinence from alcohol in alcoholic cirrhosis); (2)Symptomatic Resolution: Regression of ascites (discontinuation of diuretics), remission of hepatic encephalopathy (discontinuation of lactulose/rifaximin), and absence of recurrent variceal bleeding (for at least 12 months); (3)Improvement in Liver Function: Stable improvement in liver function tests (albumin, INR, bilirubin). Assessed via lab tests (HCV RNA, HBV DNA, albumin, INR, bilirubin) and clinical evaluation (ascites, encephalopathy, endoscopy). Reported as binary (Yes/No).	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The secondary endpoints were severe variceal recurrence and mortality during the 2-year follow-up	The recurrence rate of the varices in the EP group will compared to that in the E group during the follow up.	2 years
Changes of the peripheral blood cell counts including white blood cell, red blood cell, and platelate counts in both group during 2-years follow up.	The physiological parameters including white blood cell (*10^9/L), red blood cell (*10^12/L) and platelte(*10^12/L) will compared between the two groups.	2 years
The secondary endpoints were changes in Child-Pugh Score, MELD Score, and Physiological Parameters during the follow-up.	Changes in liver function (Child-Pugh score, MELD score) and physiological parameters (white blood cell count [*10^9/L], red blood cell count [*10^12/L], platelet count [*10^12/L], hemoglobin [g/dL], and coagulation parameters) will be assessed and compared during the 1-year follow-up between the two groups.	2 years

Collaborators and Investigators

• Sponsor: Yanjing Gao
• Collaborators: Shandong Provincial Hospital; Jinan Military General Hospital
• Investigators: Principal Investigator: Yanjing Gao Yanjing Gao, PhD.MD, Qilu Hospital,Shandong Universty

Publications and helpful links

General Publications

• Sun X, Zhang A, Zhou T, Wang M, Chen Y, Zhou T, Chen X, Xiu A, Peng Z, Cheng B, Liu X, Gao Y. Partial splenic embolization combined with endoscopic therapies and NSBB decreases the variceal rebleeding rate in cirrhosis patients with hypersplenism: a multicenter randomized controlled trial. Hepatol Int. 2021 Jun;15(3):741-752. doi: 10.1007/s12072-021-10155-0. Epub 2021 Feb 27.

Study record dates

Study Major Dates

• Study Start: February 1, 2016
• Primary Completion (Actual): December 1, 2019
• Study Completion (Actual): January 1, 2020

Study Registration Dates

• First Submitted: May 8, 2016
• First Submitted That Met QC Criteria: May 17, 2016
• First Posted (Estimated): May 19, 2016

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 11, 2025
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Portal hypertension; Non-selective beta-blocker; Thrombocytopenia; Gastroesophageal varices; Hypersplenism; Secondary prophylaxis; Endoscopic variceal ligation; Partial splenic embolization; hepatic recompensation
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Digestive System Diseases; Liver Diseases; Hypertension; Fibrosis; Liver Cirrhosis; Hypertension, Portal; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neurotransmitter Agents; Adrenergic Agents; Adrenergic Antagonists; Adrenergic beta-Antagonists; Somatostatin
• Other Study ID Numbers: 201602-QILU

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All the individual participant data (IPD) available to other researchers.
• IPD Sharing Time Frame: 2021.1
• IPD Sharing Access Criteria: Open Access
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• product manufactured in and exported from the U.S.: No