In this RCT, we attempted to prove the superiority of vonoprazan to lansoprazole in the healing rate after gastric ESD in patients stratified according to the ESD ulcer index. Unfortunately, vonoprazan was not superior to lansoprazole in terms of the healing rates and shrinkage rates of artificial gastric ulcers at 4 and 8 weeks after ESD. Furthermore, there were no significant differences in the occurrence of postoperative bleeding and delayed perforation between the two groups.
Some RCTs suggested that vonoprazan was as effective as PPIs in the treatment of ESD-induced ulcer [13–15]. Our results were consistent with those previously reported, in which the healing rates at 4 weeks in the vonoprazan groups ranged 7.4–20.9%. Our hypothesis was that the strong and rapid inhibition of gastric acid secretion by vonoprazan may enhance the healing of artificial ulcers. However, the effect of ulcer shrinkage in the vonoprazan group was similar to that noted in the PPI group. There may be two reasons for this result. Firstly, acid suppression by both vonoprazan and lansoprazole are excellent at shrinking artificial ulcers. Secondly, other factors than acid suppression are involved in the rapid resolution of ulcer. These factors include the existence of ulcer scar, ulcer area, ulcer site, blood coagulation status, Helicobacter pylori infection, and other comorbidities.
On the other hand, some studies concluded that vonoprazan was superior to PPIs for healing ESD-induced ulcers [16–19]. However, there were few prospective, randomized controlled studies conducted. Tsuchiya et al. reported that the vonoprazan group had a significantly superior shrinkage rate at 8 weeks; however, there was no significant difference observed in the rate of postoperative bleeding . In this prospective study, the shrinkage rates until 6 weeks were not significantly different. However, the 8-week shrinkage rate was significantly higher in the vonoprazan group versus the PPI group. In a systematic review and network meta-analysis, the effect of vonoprazan at 8 weeks was superior to that of PPIs for the treatment of artificial ulcers following ESD . However, another meta-analysis reported that the healing rate at 8 weeks was significantly higher in the PPI group versus the vonoprazan group . Thus, the effect of vonoprazan remains controversial and further RCTs are warranted. Although the primary endpoint did not meet, we believe the findings of our study are meaningful.
In this investigation, only three patients in the PPI group developed postoperative bleeding. In the 5 RCTs (including this trial) conducted thus far, the rate of postoperative bleeding in the vonoprazan group range 0-5.4%. Although the backgrounds of the study differ, the postoperative bleeding rate was equal or lower in the vonoprazan group versus the PPI group in all studies. Hamada et al. showed that vonoprazan efficaciously reduced the delayed bleeding rate in patients with an ESD-induced gastric ulcer in comparison with the threshold rate recorded using binomial testing . A larger-scale study with postoperative bleeding as its primary endpoint or meta-analysis using RCTs may prove the efficacy of vonoprazan against this complication.
There were some limitations in this study. Firstly, this study was conducted in a single center in Japan and sample size was small. Secondly, patients receiving antithrombotic agents were excluded. As postoperative bleeding was associated with administration of antithrombotic agents, its rate may be underestimated in this study.