Clinical trial NCT06836778: Comparative Study of Carvedilol Monotherapy Versus Combination Therapy With Endoscopic Variceal Ligation (EVL) for Primary Prophylaxis of Variceal Bleeding in Patients With Hepatocellular Carcinoma With High-Risk Esophageal Varices
Official title: Comparative Study of Carvedilol Monotherapy Versus Combination Therapy With Endoscopic Variceal Ligation (EVL) for Primary Prophylaxis of Variceal Bleeding in Patients With Hepatocellular Carcinoma With High-Risk Esophageal Varices: A Randomized Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Hepatocellular Carcinoma
Lead sponsor: Institute of Liver and Biliary Sciences, India
Sponsor class: OTHER
First posted: 2025-02-20
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Esophageal varices are common in patients with hepatocellular carcinoma (HCC), with an incidence rate of 63% at the time of HCC diagnosis. Following an acute variceal bleed, the 6-week mortality rate for HCC patients is as high as 26%. Mortality rates escalate notably in HCC patients experiencing acute variceal bleeding, especially with increasing cancer severity indicated by BLCL status. Research suggests that the cumulative incidence rate of variceal bleeding at one year in patients receiving primary prophylaxis is almost half that of patients not receiving any prophylaxis.

Beta blockers are the standard therapy for primary prophylaxis in patients with portal hypertension to prevent variceal bleeding. Endoscopic band ligation has also shown promising results in recent studies. However, the combined impact of beta blockers and esophageal band ligation on lowering the incidence of variceal bleeding remains unstudied.

The aim of this study is to compare the efficacy of carvedilol monotherapy versus combination therapy with carvedilol and endoscopic band ligation in patients with HCC for primary prophylaxis of high-risk esophageal varices.

Detailed description: Study population: All patients aged ≥ 18 years and ≤ 80 years admitted in Institute of Liver and Biliary Sciences, New Delhi with HCC of any cause and high risk esophageal varices and are giving written consent for participation in the study.

Study design - Single center, Open label, Randomized controlled trial Study period - 6 months Intervention - The patients will be randomized into Group -A (NSBB arm) and Group-B (EVL + NSBB arm). Both the group will receive the remaining treatment as per protocol Group A: Non-selective beta blocker (Carvedilol 3.125 mg BD for 3 days followed by 6.25 mg BD , maximum dose would be 12.5 mg BD , same shall be switch to maximum tolerable dose if SBP\< 90 , H,R\<55) Group B: Non-selective beta blocker (Carvedilol 3.125 mg BD for 3 days followed by 6.25 mg BD , maximum dose would be 12.5 mg BD , same shall be switch to maximum tolerable dose if SBP\< 90 , H,R\<55) + EVL every 3 weeks till eradication of varices followed by every 3 months.

Monitoring and assessment: Monitoring and evaluation would be done once a month for first 3 months then at 6th month.

Eligibility criteria: Inclusion Criteria:

1. Age 18-80 years
2. Cirrhosis with HCC
3. High risk oesophageal varices (\*large or small with RCS)
4. Valid consent

Exclusion Criteria:

1. Any contra-indication to beta-blockers
2. Any EVL or Sclerotherapy within last 3 months
3. Any past history of TIPS or surgery for portal hypertension
4. HCC with BCLC-D
5. Patients with past history of variceal bleed.
6. Patient With Liver transplant expected in next 2 weeks would be excluded

Primary outcomes:
measure: Proportion of patients of cirrhosis with HCC and high risk oesophageal varices on carvedilol developing variceal bleed with or without EVL in 6months follow up.
timeFrame: 6 months
Secondary outcomes:
measure: Proportion of patient developing variceal bleed while on therapy with Tyrosine Kinase Inhibitors despite on carvedilol with or without EVL
timeFrame: 6 months
measure: Proportion of patient developing variceal bleed while on therapy with immunotherapy despite on carvedilol with or without EVL.
timeFrame: 6 months
measure: Percentage of patient of cirrhosis with HCC and Portal Vein Tumoral Thrombosis developing variceal bleed while on carvedilol with or without EVL.
timeFrame: 6 months
measure: Proportion of patients having post-EVL ulcer bleed after endoscopic variceal ligation.
timeFrame: 6 months
measure: Proportion of patients with change in non invasive test for portal hypertension in both groups.
timeFrame: 6 months
measure: Proportion of patient developing variceal bleed after SBRT for advanced Hepatocellular carcinoma
timeFrame: 6 months
Other outcomes:
Locations:
city: New Delhi
country: India
facility: Institute of Liver & Biliary Sciences (ILBS)
state: Delhi
Study officials:
References: