CHICAGO—The oral potassium-competitive acid blocker vonoprazan was found to provide the same protection against rebleeding of peptic ulcer hemorrhage after endoscopic treatment as an IV proton pump inhibitor in a noninferiority trial.
The current 2021 American College of Gastroenterology guidelines recommend either continuous IV PPI therapy or intermittent oral PPI therapy for three days after successful endoscopic hemostasis (Am J Gastroenterol 2021;116[5]:899-917).
In this study, “the first multicenter randomized comparison of oral vonoprazan [Phathom] to an IV PPI for bleeding control,” according to investigator Tanawat Geeratragool, MD, patients with upper gastrointestinal bleeding were randomized to receive 20 mg of vonoprazan twice daily or 80 mg of pantoprazole followed by an infusion of 8 mg per hour. After 72 hours, those receiving the P-CAB were switched to a 20-mg once-daily dose, and those receiving a PPI were switched to 20 mg of oral omeprazole twice daily. All patients remained on the assigned acid-lowering therapies for 28 days.
Of the 174 patients recruited, 166 completed the study. The groups were well matched with respect to age, use of antithrombotics, severity of bleeding, comorbidities and stage of ulcers, said Dr. Geeratragool, from Mahidol University Faculty of Medicine, in Bangkok.
Primary, Secondary Outcomes Noninferior
On the primary outcome of rebleeding within 30 days, the rates were 4.5% versus 9.3% for the P-CAB and IV PPI, respectively. A superiority analysis was not conducted, but noninferiority (within a margin of 10%) was confirmed at a level of high statistical significance (P=0.0005), reported Dr. Geeratragool, who presented the data at the 2023 Digestive Disease Week (abstract 614).
More favorable outcomes for the P-CAB, leading to highly significant confirmation of noninferiority (also within the 10% margin), also were met for the secondary end points of bleeding rates within three days (1.14% vs. 5.81%; P=0.0001) and bleeding within seven days (3.41% vs. 6.98%; P=0.0006).
Repeat endoscopic treatment was performed in 4.55% of patients in the P-CAB group and 9.30% of those in the IV PPI group. No patients in either group required surgical rescue, but one in the IV PPI group and none in the P-CAB group required a rescue embolization. There were no cases of bleeding-related mortality in either group, but the all-cause mortality rates at 30 days were 5.68% in the P-CAB group and 9.30% in the IV PPI group.
After endoscopic hemostasis, 0.88 units of blood was transfused in the P-CAB group versus 1.44 units in the IV PPI group. The lower number of days in the hospital among those randomized to the P-CAB (6.89 vs. 9.41 days) was associated with a statistical trend (P=0.08) in favor of the P-CAB.
The opportunity for an earlier discharge with oral therapy is one of the potential advantages of a P-CAB over the current standard of IV PPI, Dr. Geeratragool noted, adding that the study was conducted on the basis of evidence that the P-CAB vonoprazan has more potent acid suppression with a faster onset of action.
Unlike many countries in Asia and South America, where vonoprazan and other P-CABs are available for treatment of acid-related diseases, including esophagitis, the only current indication for this agent in the United States is within a combination regimen for eradication of Helicobacter pylori. Clinical trials are underway for additional indications.
Western Populations May Need Different Dosing
For preventing rebleeding after endoscopic hemostasis, the 80-mg IV dose of a PPI followed by an infusion of 8 mg per hour is supported by “the highest quality evidence” that includes an association with a mortality benefit, according to John R. Saltzman, MD, the director of endoscopy at Brigham and Women’s Hospital, in Boston.
Although the most recent guidelines allow high-dose oral PPI as an alternative, Dr. Saltzman pointed out that one strength of this noninferiority study, conducted in Thailand, is that vonoprazan was compared with an established standard.
However, there are potential differences between acid-lowering therapies for Asian and non-Asian populations. “In interpreting these results,” Dr. Saltzman said, “it is important to note that Western populations may require higher doses of PPIs, reportedly due to lesser pharmacodynamic and clinical effects of PPIs.”
—Ted Bosworth
Drs. Geeratragool and Saltzman reported no relevant financial disclosures. The trial was funded by Phathom.
This article is from the September 2023 print issue.