Esophageal and Gastric Varices, Liver Cirrhosis
Conditions
Keywords
esophageal and gastric varices, endoscopic therapy, adverse events, liver cirrhosis, proton pump inhibitor
Brief summary
Traditionally, it is considered that gastric acid delays ulcer healing, and acid suppression can reduce the risk of post-banding ulcer bleeding and promote mucosal healing at the ulcer site. A systematic review and meta-analysis performed by our team demonstrated that acid suppression significantly reduced the incidence of gastrointestinal bleeding (GIB) following prophylactic endoscopic variceal ligation (EVL), but had no significant effect on the incidence of mortality, adverse events, or length of stay. Similarly, another systematic review and meta-analysis performed by Lin et al. indicated that proton pump inhibitor (PPI) significantly reduced the incidence of GIB after therapeutic or prophylactic endoscopic variceal treatment (EVT), and the efficacy of PPI in reducing post-EVT GIB is related to the duration of PPI. However, previous studies have indicated that long-term use of PPI may increase the risk of bacterial infections and hepatic encephalopathy in patients with cirrhosis. Therefore, current guidelines suggest that PPI should be discontinued after EVT, unless the patient has a clear indication for PPI. However, the quality of evidence is poor due to the small sample sizes, predominantly retrospective designs, and inconsistencies in follow-up duration of previous studies. In current clinical practice, most physicians still prefer to use PPI routinely after EVT to prevent post-EVT GIB. Given the ongoing controversy regarding the routine use of PPI after EVT, we plan to conduct a multicenter randomized controlled trial to to explore the effect of PPI after prophylactic EVT on the incidence of short-term GIB, adverse events, and mortality in patients with cirrhosis and esophagogastric varices (EGV).
Detailed description
Overall, 208 patients with cirrhosis and EGV undergoing prophylactic EVT will be enrolled. They will be randomly assigned at a ratio of 1:1 to the pantoprazole group and the control group. The primary endpoint is 6-week GIB. The secondary endpoints include: (1) 6-week all-cause death; (2) hierarchical composite endpoint of all-cause death or 6-week GIB. The safety outcome is 6-week adverse events, which contains complications potentially related to EVT or PPI within 6 weeks after EVT.
Interventions
DRUGPantoprazole
Participants assigned to the pantoprazole group should receive intravenous pantoprazole 40 mg once daily immediately after EVT for a duration of 1 to 7 days until discharge, followed by oral pantoprazole 40 mg once daily until the total duration is 2 weeks. Patients assigned to the control group should not receive any acid suppression.
Sponsors
General Hospital of Shenyang Military Region
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. patients who are diagnosed with liver cirrhosis by liver biopsy and/or a combination of clinical manifestation, laboratory tests, and imaging examinations; 2. patients who are diagnosed with esophageal varix (EV) or gastroesophageal varix 1 (GOV1) by endoscopy; 3. patients who undergo EVT for EV and/or gastric varices; 4. patients who undergo EVT for either primary or secondary prophylaxis of EVB; 5. patients aged ≥18 years, regardless of gender; 6. patients who sign their informed consent forms.
Exclusion criteria
1. patients with a diagnosis of acute variceal bleeding before enrollment; 2. patients with definite indications for PPI (reflux esophagitis, peptic ulcer, Zollinger-Ellison syndrome, etc.) at admission; 3. patients with definite indications for PPI (reflux esophagitis, peptic ulcer, etc.) discovered during EVT; 4. patients who are allergic to PPI or had intolerable adverse reactions to PPI previously; 5. patients with severe cardiovascular diseases, cerebrovascular diseases, or renal impairment; 6. patients with severe hematological disorders; 7. patients who were pregnant, lactating, or preparing for pregnancy; 8. patients who have already participated in other clinical trials.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of 6-week GIB | 6 weeks | binary outcome |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of 6-week all-cause death | 6 weeks | time-to-event outcome |
| Proportion of 6-week adverse events | 6 weeks | Proportion of 6-week adverse events (binary outcome) is also the safety outcome, which is defined as complications potentially related to EVT or PPI within 6 weeks after EVT. The complications related to PPI primarily include: (1) clostridium difficile infection; (2) pneumonia; (3) hepatic encephalopathy; (4) spontaneous bacterial peritonitis; and (5) other adverse events. Except for GIB, the complications related to EVT primarily include: (1) retrosternal pain/discomfort; (2) nausea/vomiting; (3) heartburn/acid regurgitation; (4) fever; (5) diarrhea; (6) abdominal pain; and (7) other adverse events. |
| hierarchical composite endpoint of all-cause death or 6-week GIB | 6 weeks | The hierarchy of the composite endpoint is death due to all cause (time-to-event) and then 6-week GIB (binary). |
Countries
China
Contacts
STUDY_DIRECTORXingshun Qi
Department of Gastroenterology, General Hospital of Northern Theater Command (formerly called General Hospital of Shenyang Military Area)
Outcome results
None listed