Primary Prevention of Patients With Hepatocellular Carcinoma and Concomitant Esophageal Varices

NCT ID: NCT01970748

Last Updated: 2019-08-30

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-08-31
• Study Completion Date: 2025-12-31

Brief Summary

Randomized comparison within the endoscopic esophageal varices ligation versus non-selective beta-blocker in the primary prevention of esophageal variceal bleeding in patients with HCC.

Detailed Description

Gastroesophageal variceal bleeding is a major complication of cirrhosis and has high rate of rebleeding and mortality. In these 20 to 30 years, medical advances have significantly improved the prognosis of variceal bleeding. Nevertheless, the mortality of gastroesophageal variceal bleeding is still nearly 20 to 30%.

Hepatocellular carcinoma (HCC) is one of the most common malignancy in Asian, and is also the special group in portal hypertension. Studies in Italy, more than 50% of patients diagnosed with HCC are concomitant with esophageal varices. HCC and portal thrombosis caused by HCC itself are all independent risk factors of gastroesophageal bleeding. Once the bleeding, rebleeding rate is up to 50% even if early use of vasoconstrictor agents and endoscopic therapy, which is generally 2 times in patients with cirrhosis.

According to 2010 Baveno V recommendations, non-selective beta-blockers (NSBB) or endoscopic variceal ligation (EVL) are first choice for primary prevention of first variceal bleeding in cirrhotic patients. However, risk factors of variceal bleeding caused by HCC or cirrhosis are different, and portal hypertension is particularly high in patients with HCC and may be combined with portal vein thrombosis. NSBB sufficient to decreased portal hypertension to prevent variceal bleeding is not clear. In Hepatology 2010, Lebrec claimed that NSBB used for cirrhotic patients with refractory ascites had poor prognosis, the main cause of death were the progression of HCC and sepsis, although the impact of NSBB for HCC patients are not entirely clear, but this issue remind clinicians to careful use of NSBB in these patients. Since NSBB possible adverse effects, the use of EVL to prevent bleeding in patents with HCC is superior to NSBB? These need further study to clarify. So we designed this study to evaluate the feasibility and effectiveness of using EVL or NSBB to prevent first bleeding in patients with HCC concomitant with esophageal varices.

Conditions

Bleeding Esophageal Varices; Hepatocellular Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Propranolol

Propranolol 10mg BID initially and titrate dosage every week to achieve 25% drop of heart rate (keep heart rate\>55 or systemic blood pressure\>90mmHg)

Group Type: PLACEBO_COMPARATOR

Propranolol

Intervention Type: DRUG

Propranolol 10mg BID initially and titrate dosage every week to achieve 25% drop of heart rate (keep heart rate\>55 or systemic blood pressure\>90mmHg)

Esophageal variceal ligation

Esophageal variceal ligation every 3-4 weeks to achieve variceal eradication under endoscopy. After eradication, follow-up endoscopy every 3 months and variceal ligation again if recurrence.

Group Type: ACTIVE_COMPARATOR

Esophageal variceal ligation

Intervention Type: PROCEDURE

Esophageal variceal ligation every 3-4 weeks to achieve variceal eradication under endoscopy

Interventions

Propranolol

Propranolol 10mg BID initially and titrate dosage every week to achieve 25% drop of heart rate (keep heart rate\>55 or systemic blood pressure\>90mmHg)

Intervention Type: DRUG

Esophageal variceal ligation

Esophageal variceal ligation every 3-4 weeks to achieve variceal eradication under endoscopy

Intervention Type: PROCEDURE

Other Intervention Names

Inderal, Cardolol; EVL

Eligibility Criteria

Inclusion Criteria

• Between 20 and 80 years old
• Hepatocellular carcinoma (HCC) associated with esophageal varices
• F2 or F3 esophageal varices (Beppu et al classification)
• Hepatocellular carcinoma (HCC) associated with portal thrombosis

Exclusion Criteria

• History of esophageal variceal bleeding
• Had received endoscopic variceal ligation (EVL) or endoscopic injection sclerotherapy (EIS)
• Pregnancy, or the patients with other terminal illness (such as other terminal cancers, heart failure, renal failure...)
• Propranolol contraindications (such as atrioventricular block, heart failure, chronic obstructive pulmonary disease, asthma, poorly controlled diabetes, severe peripheral arterial disease...)

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Taipei Veterans General Hospital, Taiwan

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ming-Chih Hou, MD

Role: PRINCIPAL_INVESTIGATOR

Taipei Veterans General Hospital, Taiwan

Locations

Taipei Veterans General Hospital

Taipei, , Taiwan

Site Status: RECRUITING

Countries

Taiwan

Central Contacts

Ming-Chih Hou, MD

Role: CONTACT

mchou@vghtpe.gov.tw

886-2-28712121 ext. 1320

Facility Contacts

Ming-Chih Hou, MD

Role: primary

mchou@vghtpe.gov.tw

886-2-28712121 ext. 1320

Han-Chieh Lin, MD

Role: backup

hclin@vghtpe.gov.tw

886-2-28712121 ext. 7506

References

Yang TC, Chen WC, Hou MC, Chen PH, Lee PC, Chang CY, Lu HS, Chen YJ, Hsu SJ, Huang HC, Luo JC, Huang YH, Lee FY. Endoscopic variceal ligation versus propranolol for the primary prevention of oesophageal variceal bleeding in patients with hepatocellular carcinoma: an open-label, two-centre, randomised controlled trial. Gut. 2024 Mar 7;73(4):682-690. doi: 10.1136/gutjnl-2023-330419.

Reference Type: DERIVED

PMID: 38123994 (View on PubMed)

Other Identifiers

V101C-016；V102C-094

Identifier Type: -

Identifier Source: org_study_id