Trial Title:
Endoscopic Variceal Ligation vs Carvedilol for the Prevention of First Esophageal Variceal Bleeding in Patients With HCC
NCT ID:
NCT06594744
Condition:
Hepatocellular Carcinoma (HCC)
Esophageal Varices
Conditions: Official terms:
Carcinoma
Carcinoma, Hepatocellular
Esophageal and Gastric Varices
Carvedilol
Conditions: Keywords:
Endoscopic variceal ligation
Hepatocellular carcinoma
Nonselective beta-blocker
Portal hypertension
Study type:
Interventional
Study phase:
Phase 4
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
EVL group:
EVL will be performed and repeated every 3 to 4 weeks until the EVs are eradicated.
Following this, patients will undergo regular upper gastrointestinal endoscopic
surveillance, initially every three months for a total of two sessions, then every six
months for a total of two sessions, and subsequently annually. If EVs are found to recur
during surveillance, additional EVL will be performed every 3 to 4 weeks until the
varices are again eradicated endoscopically.
Carvedilol group:
The initial dosage of carvedilol is set at 6.25 mg daily. In the absence of hypotension
(systolic blood pressure < 90 mmHg), bradycardia (resting heart rate
< 55 beats per minute), or other adverse effects, hospitalized patients may
have their dosage increased to 12.5 mg daily after 3 days, while outpatient patients may
increase their dosage to 12.5 mg daily after 7 days. This dosage represents the target
dose for the trial.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Endoscopic variceal ligation
Description:
EVL will be performed and repeated every 3 to 4 weeks until the EVs are eradicated.
Following this, patients will undergo regular upper gastrointestinal endoscopic
surveillance, initially every three months for a total of two sessions, then every six
months for a total of two sessions, and subsequently annually. If EVs are found to recur
during surveillance, additional EVL will be performed every 3 to 4 weeks until the
varices are again eradicated endoscopically.
Arm group label:
Endoscopic variceal ligation
Intervention type:
Drug
Intervention name:
Carvedilol
Description:
The initial dosage of carvedilol is set at 6.25 mg daily. In the absence of hypotension
(systolic blood pressure < 90 mmHg), bradycardia (resting heart rate < 55 beats per
minute), or other adverse effects, hospitalized patients may have their dosage increased
to 12.5 mg daily after 3 days, while outpatient patients may increase their dosage to
12.5 mg daily after 7 days. This dosage represents the target dose for the trial.
Arm group label:
Carvedilol
Summary:
The goal of this clinical trial is to evaluate whether endoscopic variceal ligation (EVL)
or carvedilol is more effective at preventing the first esophageal variceal bleeding
(EVB) in patients with hepatocellular carcinoma (HCC). It will also learn about the
safety of EVL and carvedilol in patients with HCC. The main questions it aims to answer
are:
Whether EVL or carvedilol is more effective at preventing initial EVB in patients with
HCC with high-risk EVs.
What medical problems do participants have when undergoing EVL or taking carvedilol?
Researchers will compare the efficacy and safety of EVL to carvedilol for the prevention
of first EVB in patients with HCC.
Participants will:
Undergo EVL every 3-4 weeks until variceal eradication and then receive regular
endoscopic follow-up according to the protocol, or Take carvedilol every day (start from
6.25 mg/d and then titrate to 12.5 mg/d if tolerable).
Visit the clinic once every 2-3 months for checkups and tests. Keep a diary of their
vital signs (SBP, DBP, and HR) as well as symptoms.
Detailed description:
Gastro-esophageal variceal bleeding is a major complication of portal hypertension (PHT)
and carries a high rate of rebleeding and mortality. Hepatocellular carcinoma (HCC), a
special subgroup of PHT, is the sixth most commonly diagnosed cancer and the third
leading cause of cancer death worldwide. The presence of esophageal varices (EVs) in more
than half of patients with HCC is associated with poor survival. Furthermore, without
primary prevention strategies, nearly half of these HCC patients experience esophageal
variceal bleeding (EVB). The prognosis of HCC patients with EVB is extremely poor, with a
rebleeding rate of 50% and a six-week mortality rate of 26-48%, both of which are higher
than those of non-HCC patients.
However, there is still a lack of evidence on how to prevent first EVB in patients with
HCC with high-risk EVs. AASLD practice guidance recommends prevention of EVB and hepatic
decompensation in patients with HCC should follow the same principles as those for
patients without HCC, that is, nonselective beta-blocker (NSBB) therapy is recommended in
patients with HCC with clinically significant portal hypertension (CSPH). Endoscopic
variceal ligation (EVL) is recommended for compensated patients with high-risk EVs who
have contraindications to NSBBs. However, this recommendation lacks randomized controlled
trial (RCT) to support it. Our recently published RCT showed that EVL is superior to
propranolol (PPL) in the primary prevention of EVB in patients with HCC with high-risk
EVs. In the subgroup analysis, EVL reduces EVB and improves OS in patients with BCLC
stage A/B but not in those with BCLC stage C/D.
Carvedilol, an NSBB that additionally exerts intrinsic anti-alpha-1-adrenergic activity,
has been shown to reduce hepatic venous pressure gradient more than propranolol and is
currently the first-line treatment for primary prophylaxis in patients with CSPH.
Nevertheless, the superiority of EVL versus carvedilol as a primary prevention strategy
in patients with HCC with high-risk EVs is still unknown. In this project, we will
initiate an open-label RCT aiming at comparing the efficacy of EVL and carvedilol in the
primary prevention of EVB in patients with HCC with high-risk EVs. We will also explore
if there is any difference between the two groups in terms of other upper
gastrointestinal bleeding, nonbleeding liver decompensation (such as new onset/worsening
ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, and hepatorenal
syndrome), overall survival, adverse events, tolerability and safety. We will also
compare the efficacy of EVL and carvedilol in the primary prevention of EVB in patients
with HCC at different BCLC stage.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patients with HCC and high-risk EVs, confirmed through imaging and clinical data
(classified as F2 or F3 EVs according to Beppu et al. classification)
Exclusion Criteria:
- Age less than 20 years or greater than 90 years.
- History of esophageal variceal bleeding.
- Previous treatment for EVs, including EVL, endoscopic sclerotherapy, transjugular
intrahepatic portosystemic shunt (TIPS), or surgical interventions.
- Use of non-selective β-blockers within two weeks prior to enrollment.
- Contraindications for non-selective β-blockers, including severe atrioventricular
block, chronic obstructive pulmonary disease (COPD), asthma, poorly controlled
diabetes, and severe peripheral artery disease.
- Presence of other end-stage organ diseases, including terminal cancers other than
HCC, heart failure, and renal failure.
- Pregnant women.
Gender:
All
Minimum age:
20 Years
Maximum age:
90 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Taipei Veterans General Hospital
Address:
City:
Taipei
Zip:
11217
Country:
Taiwan
Contact:
Last name:
Tsung-Chieh Yang, MD
Phone:
+886-2-28712121
Phone ext:
7506
Email:
tcyang@vghtpe.gov.tw
Contact backup:
Last name:
Ming-Chih Hou, MD
Phone:
+886-2-28712121
Phone ext:
7053
Email:
mchou@vghtpe.gov.tw
Investigator:
Last name:
Tsung-Chieh Yang, MD
Email:
Principal Investigator
Start date:
October 2024
Completion date:
October 2030
Lead sponsor:
Agency:
Taipei Veterans General Hospital, Taiwan
Agency class:
Other
Source:
Taipei Veterans General Hospital, Taiwan
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06594744
