P-HCC: Primary Prevention of Patients With Hepatocellular Carcinoma and Concomitant Esophageal Varices

Sponsor

Taipei Veterans General Hospital, Taiwan (Other)

Overall Status

Recruiting

CT.gov ID

NCT01970748

Collaborator

(none)

200

Enrollment

Location

Arms

197

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Bleeding Esophageal Varices Hepatocellular Carcinoma	Drug: Propranolol Procedure: Esophageal variceal ligation	Phase 4

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Endoscopic Treatment Versus Propranolol for Primary Prevention of Patients With Hepatocellular Carcinoma and Concomitant Esophageal Varices

Study Start Date :

Aug 1, 2009

Anticipated Primary Completion Date :

Dec 25, 2023

Anticipated Study Completion Date :

Dec 31, 2025

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: 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)	Drug: 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) Other Names: Inderal, Cardolol
Active Comparator: 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.	Procedure: Esophageal variceal ligation Esophageal variceal ligation every 3-4 weeks to achieve variceal eradication under endoscopy Other Names: EVL

Arm

Intervention/Treatment

Placebo Comparator: 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)

Drug: 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)

Other Names:

Inderal, Cardolol

Active Comparator: 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.

Procedure: Esophageal variceal ligation

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

Other Names:

EVL

Outcome Measures

Primary Outcome Measures

Bleeding [2 years]

Secondary Outcome Measures

Complication survival [2 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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...)