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

NCT05629845 | Recruiting

• 1 other identifier: 2022.410
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Variceal Bleeding; Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• 90-day death adjusted cumulative incidence of variceal rebleeding after secondary prevention by EUS-guided therapy or conventional endoscopic therapy

  Cumulative incidence of variceal rebleeding at 90-day after study procedures will be analyzed after adjustment of incidence of death from HCC or cirrhosis

  From day of study procedure to day 90 after study procedure

Secondary Outcomes (3)

• 30-day death adjusted cumulative incidence of variceal rebleeding after secondary prevention by EUS-guided therapy or conventional endoscopic therapy

  From day of study procedure to day 30 after study procedure

• bleeding-free survival at 3 months after secondary prevention by EUS-guided therapy or conventional endoscopic therapy

  From day of study procedure to 3 months after study procedure

• procedure related adverse events within 30 days of secondary prevention

  From day of study procedure to day 30 after study procedure

Study Arms (2)

EUS-guided therapy group

ACTIVE COMPARATOR

EUS would be performed with a curvilinear echoendoscope based on protocol described in our prior study. Because EUS-guided glue injection can be applied to both EV and GV and is less technically demanding than coiling or the combination approach, it is chosen as the EUS guided intervention in our study. The target EV or GV size will be measured by the caliper function on the EUS machine. After confirmation of blood flow in the target varix by Doppler, EUS-guided glue injection would be performed for EV or GV ≥ 3mm in diameter using a standard 19G needle. Each injection will contain a 1.2ml mixture of 0.5ml glue (Histoacryl, n-butyl-2-cyanoacrylate, B. Braun Surgical, Germany) + 0.7ml lipiodol. Flow obliteration in the treated varix will be confirmed on EUS Doppler. If blood flow is still observed on Doppler after the first injection, additional injection of glue-lipiodol mixture would be repeated (up to 4 doses) until flow obliteration is achieved.

Procedure: endoscopic ultrasound-guided therapy

Conventional endoscopic therapy group

ACTIVE COMPARATOR

In patients with prior EV bleeding, EV with high-risk stigmata (regardless of size) or EV of medium or large size detected on study EGD will be treated with VBL using a multi-band ligator fitted on the gastroscope for secondary prevention. In patients with prior GV bleeding, if compressible GV suggestive of incomplete obliteration from prior glue treatment is noted on study EGD, cyanoacrylate glue injection using a 1.2ml mixture of 0.5ml glue (Histoacryl, n-butyl-2-cyanoacrylate, B. Braun Surgical, Germany) + 0.7ml lipiodol will be performed for secondary prevention.

Procedure: conventional endoscopic therapy

Interventions

endoscopic ultrasound-guided therapy PROCEDURE

EUS-guided glue injection will be used for secondary prevention of EV or GV rebleeding.

EUS-guided therapy group

conventional endoscopic therapy PROCEDURE

conventional endoscopic therapy (VBL for EV or glue injection for GV) for secondary prevention of EV or GV rebleeding.

Conventional endoscopic therapy group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Chinese University of Hong Kong: lead

Study Sites (1)

Prince of Wales Hospital, The Chinese University of Hong Kong

Shatin, New Territories, Hong Kong

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Raymond S Tang, MD

  Chinese University of Hong Kong

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Raymond S Tang, MD

CONTACT

(852) 26370428; raymondtang@cuhk.edu.hk

Felix Sia, BS

CONTACT

(852) 26370428; felixsia@cuhk.edu.hk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: randomized controlled trial

Study Record Dates

• First Submitted: November 18, 2022
• First Posted: November 29, 2022
• Study Start: November 22, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: March 19, 2026

Record last verified: 2026-03

Locations

HK (1)