Prevention of Variceal Rebleeding by EUS-guided vs Conventional Endoscopic Therapy in Hepatocellular Carcinoma Patients

Trial Title: Prevention of Variceal Rebleeding by EUS-guided vs Conventional Endoscopic Therapy in Hepatocellular Carcinoma Patients

NCT ID: NCT05629845

Condition: Hepatocellular Carcinoma
Variceal Bleeding

Conditions: Official terms:
Carcinoma
Carcinoma, Hepatocellular

Study type: Interventional

Study phase: N/A

Overall status: Recruiting

Study design:

Allocation: Randomized

Intervention model: Parallel Assignment

Intervention model description: randomized controlled trial

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Procedure
Intervention name: endoscopic ultrasound-guided therapy
Description: EUS-guided glue injection will be used for secondary prevention of EV or GV rebleeding.
Arm group label: EUS-guided therapy group

Intervention type: Procedure
Intervention name: conventional endoscopic therapy
Description: conventional endoscopic therapy (VBL for EV or glue injection for GV) for secondary prevention of EV or GV rebleeding.
Arm group label: Conventional endoscopic therapy group

Summary: Rebleeding rate is high in hepatocellular carcinoma (HCC) patients with variceal bleeding despite conventional endoscopic therapies for esophageal and gastric varices (EV, GV). Secondary prevention of variceal rebleeding was reported to improve outcomes of HCC patients, but the optimal endoscopic approach is not well defined. In this difficult-to-manage population, variceal rebleeding rates remain substantial after conventional endoscopic therapies. n recent studies by others and our group on direct EUS-guided therapy for varices in cirrhotic patients, high technical success (90 - 100%), low post-treatment rebleeding rate (3 - 11%) and low adverse event rate (~3%) have been reported for GV treatment by cyanoacrylate glue injection, coiling or a combination of both, and for cyanoacrylate glue injection or coiling of EV refractory to variceal band ligation (VBL). This study aims to compare rebleeding rates after secondary prevention by EUS-guided therapy or conventional endoscopic therapy in HCC patients with recent variceal bleeding.

Detailed description: Chronic liver diseases and cirrhosis are common health problems in the Asia-Pacific region. In 2015, 54.3% of global deaths due to cirrhosis occurred in the Asia-Pacific region. Acute variceal bleeding is a life-threatening complication of cirrhosis that occurs at a rate of 10 - 15% per year, with a 6-week mortality rate up to 25%. In patients with successful acute bleeding control by endoscopic therapy and vasoactive agents, rebleeding is common in those without subsequent secondary prevention by non-selective beta blocker and/or endoscopic therapy (e.g. variceal band ligation (VBL) for esophageal varices (EV) and glue injection for gastric varices (GV)). Apart from variceal bleeding, hepatocellular carcinoma (HCC) (liver cancer) is another important complication of cirrhosis. HCC patients with prior variceal bleeding are at high risk of rebleeding due to significant portal hypertension and frequent presence of portal vein thrombosis (PVT). In this difficult-to-manage population, variceal rebleeding rates remain substantial after conventional endoscopic therapies. In a large multicenter study comparing clinical outcomes after EV bleeding in patients with or without HCC, lack of secondary prevention for rebleeding was found to be frequent in HCC patients and was associated with a higher rate of rebleeding and mortality. In HCC patients with EV bleeding, secondary prevention failure by conventional endoscopic therapy was significantly higher (50% vs 31%, P = 0.001) when compared with patients without HCC. However, the optimal endoscopic approach for secondary prevention in HCC patients has not been well defined. Whether commonly used endoscopic techniques such as VBL for EV and cyanoacrylate glue injection for GV being performed at intervals of 3 - 4 weeks for secondary prevention can achieve durable variceal control in HCC patients remains unclear. Direct endoscopic ultrasound (EUS)-guided variceal interventions by cyanoacrylate glue injection, coiling, or a combination of both using a therapeutic curvilinear echoendoscope is a novel endoscopic technique that have attracted clinical attention due to its high efficacy in variceal control. In recent studies by others and our group on direct EUS-guided therapy for varices in cirrhotic patients, high technical success (90 - 100%), low post-treatment rebleeding rate (3 - 11%) and low adverse event rate (~3%) have been reported for GV treatment by cyanoacrylate glue injection, coiling or a combination of both, and for cyanoacrylate glue injection or coiling of EV refractory to VBL. In a retrospective study published by our group in 2020, we compared outcomes in 27 HCC patients with variceal bleeding who underwent secondary prevention by EUS-guided glue injection every 12 weeks and 33 HCC patients without secondary prevention after control of acute variceal bleeding. The technical success of EUS-guided therapy was 100%. The overall procedure-related adverse event rate was low (3.7%) and no radiographic evidence of glue-lipiodol embolization was observed. The EUS-guided therapy group was found to have a significantly lower 90-day death-adjusted cumulative incidence of rebleeding and a significantly higher variceal bleeding-free survival at 3 and 6 months. As such, it would be clinically important to conduct a prospective randomized controlled study to confirm the benefits of EUS-guided therapy for secondary prevention in HCC patients.

Criteria for eligibility:
Criteria:
Inclusion Criteria: - Consecutive HCC patients age 18 or older with recent (within 4 weeks of the episode) EV or GV bleeding successfully controlled by conventional endoscopic therapies (VBL for EV or glue injection for GV) - Able to provide written informed consent to participate in the study and comply with the study procedures Exclusion Criteria: - Unable to provide written informed consent - Contraindications for endoscopy due to underlying comorbidities - HCC patients with non-variceal source of gastrointestinal bleeding - Refractory coagulopathy (INR>1.5) or refractory thrombocytopenia (platelets <50,000) despite blood product transfusion - Moribund patients from terminal illness

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Prince of Wales Hospital, The Chinese University of Hong Kong

Address:
City: Sha Tin
Country: Hong Kong

Status: Recruiting

Contact:
Last name: Felix Siz, BS

Phone: (852) 26370428
Email: felixsia@cuhk.edu.hk

Investigator:
Last name: Raymond S Tang, MD
Email: Principal Investigator

Start date: November 22, 2022

Completion date: May 1, 2026

Lead sponsor:
Agency: Chinese University of Hong Kong
Agency class: Other

Source: Chinese University of Hong Kong

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05629845