Clinical trial NCT05859009: Primary Prevention of Gastric Varices Bleed
Official title: EUS-guided Therapy vs Non-selective Beta Blocker for the Primary Prophylaxis of Gastric Varices Bleed: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Gastric Varices Bleeding
Endoscopic Ultrasound
Lead sponsor: Unity Health Toronto
Sponsor class: OTHER
First posted: 2023-05-15
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: PREVENTION

Brief summary: Primary prophylaxis of gastric varices is an important area of research, as gastric varices are a common complication of cirrhosis of the liver. Cirrhosis is a condition in which the liver becomes scarred and loses its ability to function properly, and it is a leading cause of morbidity and mortality worldwide. Gastric varices occur in up to 30% of patients with cirrhosis, and they can rupture, leading to life-threatening bleeding. The clinical, epidemiological, and public health context of primary prophylaxis of gastric varices is therefore the need to prevent the development of this complication in patients at risk for cirrhosis and to reduce the associated morbidity and mortality. The clinical trials on primary prophylaxis of gastric varices are therefore focused on evaluating the safety and efficacy of various interventions, such as beta-blockers and endoscopic techniques, in reducing the risk of gastric varices in patients with cirrhosis. The goal of this trial is to find the most effective and safe strategies for primary prophylaxis of gastric varices, in order to improve the outcomes for patients with cirrhosis.

Detailed description: Primary gastric varices (GV) are a condition that affects 17% of patients with liver cirrhosis who have not previously received treatment, either endoscopic or pharmacologic. Although the incidence of GV is lower than oesophageal varices (EV) and the bleeding rate is also less frequent, GV bleeding is more severe and is associated with higher re-bleeding and death rates when compared to EV. The management of acute GV bleeding is well established, but the primary prophylaxis (PP) for certain types of GV remains unclear. The management of GOV-1 (gastroesophageal varices type 1) is recommended as for EV, but for isolated gastric varices type 1 (IGV-1) and gastroesophageal varices type 2 (GOV-2), PP is not clearly defined. Existing guidelines from the American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL) do not provide strong recommendations for primary prophylaxis of IGV-1/GOV-2. While EASL suggests the use of nonselective beta-blockers (NSBB) for IGV-1/ GOV-2 based on one Randomized Controlled Trial (RCT) from 2011 on 89 patients, comparing NSBB vs. endoscopic glue injection for primary prophylaxis in GOV-2/IGV-1. The Baveno consensus VII recommends NSBB in PP but emphasizes the need for further studies. However, no study compares NSBB vs. EUS-GV management in primary prophylaxis. Establishing primary prophylaxis for IGV-1/GOV-2 is even more important as the 2-year incidence of variceal bleeding from IGV1 and GOV-2 type of varices is more frequent and profuse (78% and 54%, respectively) than the lesser curve (GOV-1) varices (28%).

Clinical research has shown that the use of non-selective beta-blockers, such as propranolol and nadolol, can be effective in reducing the risk of developing gastric varices in patients with cirrhosis. These medications work by reducing blood flow to the dilated veins in the stomach, thereby reducing the pressure in these vessels. In addition to the use of beta-blockers, there have been other interventions studied for primary prophylaxis of gastric varices. These include the use of endoscopic techniques such as band ligation and injection sclerotherapy, and the use of the cyanoacrylate glue.

Eligibility criteria: Inclusion Criteria:

* Patients 18 years or older
* Referred to St. Michael's Hospital (SMH) for esophagogastroduodenoscopy (EGD) screening for varices
* Patients with GOV-2 or IGV-1 varices with the size ≥ 10 mm

Exclusion Criteria:

* Age \>75 and \< 18 years
* Pregnancy
* Contraindications to beta-blockers and cyanoacrylate injection
* Prior treatment for prevention of bleeding from patients on beta-blockers
* Hepatic encephalopathy grade III/IV
* Hepatorenal syndrome, hepatocellular carcinoma, presence of deep jaundice (serum bilirubin \>170 mmol/L)
* Cardiorespiratory failure
* Co-existing large oesophageal varices which require endoscopic intervention
* Child-Pugh C (score of 10-15 indicating decompensated disease)
* Presence of serious complications of liver cirrhosis

Primary outcomes:
measure: Assessment of NSBB (Propanolol), EUS-guided combined therapy (coils + glue) of GOV-2 and IGV-1
timeFrame: 3 months
measure: Assessment of NSBB (Propanolol), EUS-guided combined therapy (coils + glue) of GOV-2 and IGV-1
timeFrame: 3 months
measure: Assessment of NSBB (Propanolol), EUS-guided combined therapy (coils + glue) of GOV-2 and IGV-1
timeFrame: 6 months
measure: Assessment of NSBB (Propanolol), EUS-guided combined therapy (coils + glue) of GOV-2 and IGV-1
timeFrame: 6 months
measure: Assessment of NSBB (Propanolol), EUS-guided combined therapy (coils + glue) of GOV-2 and IGV-1
timeFrame: 9 months
measure: Assessment of NSBB (Propanolol), EUS-guided combined therapy (coils + glue) of GOV-2 and IGV-1
timeFrame: 9 months
Secondary outcomes:
measure: Estimation if any of the study arms is better for regression in size of varix
timeFrame: 3 months
measure: Estimation if any of the study arms is better for regression in size of varix
timeFrame: 6 months
measure: Estimation if any of the study arms is better for regression in size of varix
timeFrame: 9 months
Other outcomes:
measure: Safety of the procedure
timeFrame: - Follow-up visit after 3 months
measure: Safety of the procedure
timeFrame: - Follow-up visit after 6 months
measure: Safety of the procedure
timeFrame: - Follow-up visit after 9 months
Locations:
Study officials:
affiliation: Unity Health Toronto
name: Samir C Grover, MD, MEd
role: PRINCIPAL_INVESTIGATOR
affiliation: Unity Health Toronto
name: Kareem Khalaf, HBSc, MD
role: STUDY_DIRECTOR
affiliation: Unity Health Toronto
name: Nikko Gimpaya, HBSc, MEd
role: STUDY_DIRECTOR
References: