Clinical trial NCT03175731
Conditions: Liver Cirrhosis Hypertension, Portal
Keywords: Gastroesophageal varices Hemorrhage
Sponsor: Yanjing Gao
Start date: 2017-05-01; Completion date: 2019-08-30
Enrollment: 106 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study is aimed at investigating the effect of PPIs on gastroesophageal varices in liver cirrhosis. Half of participants will receive PPI, while the other half will receive a placebo.

Detailed description:
PPIs can inhibit parietal cell H+/K+-ATPase and reduce secretion of gastric acid. PPIs can promote platelet aggregation and stabilize the formation of fibrin thrombosis by maintaining the high pH environment in the stomach and inactivating pepsin. The effect of PPIs on ulcerative upper gastrointestinal bleeding was confirmed but it is not clear whether PPIs is applicable in esophagogastric variceal bleeding whose etiology and bleeding position are different from ulcerative upper gastrointestinal bleeding. There is lack of consensus and sufficient evidences to support to use PPIs in esophagogastric variceal bleeding in cirrhotic patients universally. Nevertheless, the use of PPIs in liver cirrhotic patients with gastroesophageal varices is common.

Arms: arm 1: Pantoprazole 40mg per day intravenously or orally for 2 weeks after endoscopic treatment. arm 2: Placebo 40mg per day intravenously or orally for 2 weeks after endoscopic treatment.
Interventions: intervention 1: Proton Pump Inhibitors intervention 2: Placebo
Intervention descriptions: intervention 1: Pantoprazole 40mg per day intravenously or orally for 2 weeks after endoscopic treatment. intervention 2: Placebo 40mg per day intravenously or orally for 2 weeks after endoscopic treatment.

Protocol documents:
Prot_SAP_000.pdf: 
Official Title: A randomized controlled study on effects of proton pump inhibitor on 
gastroesophageal varices of cirrhosis 
Brief Title: PPIs and Gastroesophageal Varices in Liver Cirrhosis 
NCT Number: 03175731 
Unique Protocol ID: 2017037-QILU 
Document Date: 29/12/2020 
 
 


Study Protocol 
 
Patients’ selection 
Cirrhotic patients with GEVs will be considered for enrollment in this randomized 
controlled study from May 2017 and June 2019. The following inclusion criteria will 
be applied: (1) age ≥ 18 years; (2) diagnosed cirrhosis based on clinical, laboratory, and 
radiological parameters and/or liver biopsy; (3) diagnosed GEVs based on endoscopy. 
The exclusion criteria: (1) acute gastrointestinal bleeding requiring emergency surgery; 
(2) acid-related disease, such as peptic ulcer disease or gastroesophageal reflux diseases; 
(3) hepatocellular carcinoma or other malignant tumor; (4) history of surgery of the 
esophagus, stomach or liver; (5) Child–Pugh grade C disease that cannot be improved 
to grade A or B; (6) preparing to be pregnant, pregnant, or breast feeding; (7) PPI 
allergies; and 8) missing informed consent. 
 
Randomization and masking 
Randomization will be performed after GEVs confirmed by endoscopy. Eligible 
patients will be randomized into PPI and non-PPI groups in a 1:1 ratio using a computer-
generated list of random numbers. The numbers will be written on papers placed in 
sealed and opaque envelopes by an independent research assistant. After confirmation 
of GEVs by endoscopy and inclusion in this study, one envelope will be opened. The 
expert endoscopists will be blinded to the randomization and patient’s data. 
 
Procedures 
An initial endoscopy will be performed with endoscopic findings classified according 
to the grading system outlined in the guidelines released by Chinese Medical 


Association[8]. After an initial endoscopy, endoscopic therapy will be undertaken 
according to updated UK guidelines [6]. All participants enrolled in this study will be 
banded every 2 weeks; however, patients who suffered from rebleeding will receive 
rescue EVL/ETA as soon as possible. Endoscopic therapy will be performed by three 
expert endoscopists with more than 10 years of relevant experience. 
After endoscopic therapy, eligible patients will be randomly assigned to the PPI group 
(receive pantoprazole 40 mg/day intravenously/orally for 14 days) or the non-PPI group 
(do not receive PPI treatment). 
 
 
Statistical Analysis Plan 
To calculate the sample size, the overall variceal bleeding rate after endoscopic therapy 
will be chosen as the primary outcome. According to published data[9], and assuming a 


22% difference in the rate of variceal bleeding between the non-PPI group (27%) and 
the PPI group (5%), at least 46 patients will be required in each group to provide 90% 
confidence in the results, with the upper limit of the one-sided 95% confidence interval 
(α=0.05, β=0.10). Moreover, assuming a flow off rate of 10%, at least 100 patients will 
be required in this study. 
Quantitative variables will be compared using Student’s t-test or Mann–Whitney U-test, 
and the  2 test or Fisher’s exact test will be used to compare qualitative variables. The 
cumulative rate of bleeding will be calculated using the Kaplan–Meier method, and log-
rank tests will be performed for comparison of differences. P values <0.05 will be 
considered statistically significant.