A randomized, double-blind study to evaluate the acid-inhibitory effect of vonoprazan (20 mg and 40 mg) in patients with proton-pump inhibitor-resistant erosive esophagitis

Abstract

Background:Standard treatment for patients with erosive esophagitis (EE) is proton-pump inhibitors (PPIs), but some patients are resistant to PPIs. We aimed to evaluate the acid-inhibitory effects and efficacy of a novel potassium-competitive acid blocker (vonoprazan) in patients with PPI-resistant EE.MethodsThis randomized, double-blind, multicenter study of vonoprazan evaluated gastric and esophageal pH over a 24-hour period as the primary endpoint and EE healing rate as the secondary endpoint. Following a 7 to 14-day run-in period (lansoprazole 30 mg treatment), patients with endoscopically confirmed PPI-resistant EE received vonoprazan 20 mg or 40 mg for 8 weeks.ResultsPatients were randomized to receive vonoprazan 20 mg (n = 9) or 40 mg (n = 10). Over a 24-hour period; both groups showed a significant increase from baseline in the percentage of time gastric pH ≥ 4, referred to as pH 4 holding time ratio (HTR): an increase from 73.21% to 96.46% in the 20 mg group, and from 69.97% to 100.00% in the 40 mg group. Increases from baseline in esophageal pH 4 HTRs were not significant. The 40 mg group showed greater increases in gastric and esophageal pH 4 HTRs compared with the 20 mg group, but differences between groups were not significant. After 8 weeks’ treatment, the healing rate in subjects with baseline EE grades A–D was 60.0% (3/5 patients) in the 20 mg group and 71.4% (5/7 patients) in the 40 mg group. Vonoprazan was generally well tolerated. One patient (40 mg group) experienced four treatment-emergent adverse events (TEAEs) (unrelated to study drug), leading to study discontinuation.ConclusionsVonoprazan 20 mg and 40 mg effectively inhibited gastric acid secretion over a 24-hour period with significantly increased gastric pH 4 HTR, and resulted in an EE healing rate > 60.0% in this study. Vonoprazan treatment may be valuable for patients with PPI-resistant EE

Randomised trial of acid inhibition by vonoprazan 10/20 mg once daily vs rabeprazole 10/20 mg twice daily in healthy Japanese volunteers (SAMURAI pH study)

“…This value is comparable to those observed in the present and other studies of vonoprazan . During 8 weeks of treatment with vonoprazan at 20 and 40 mg/day that followed 7 to 14 days of treatment with lansoprazole, considerable rises of blood gastrin level (maximum of 3000 and 7000 pg/mL, respectively) were reported . This finding is consistent with the trend towards a greater increase of gastrin observed during treatment with vonoprazan following rabeprazole in the present study, to which extraordinary responses of some subjects to vonoprazan might be contributory.…”

“…In a study of 24‐week maintenance therapy with vonoprazan 10 mg OD in 60 patients with healed GERD, the mean blood gastrin level was 1059 pg/mL, while no serious adverse drug reactions occurred . This value is comparable to those observed in the present and other studies of vonoprazan . During 8 weeks of treatment with vonoprazan at 20 and 40 mg/day that followed 7 to 14 days of treatment with lansoprazole, considerable rises of blood gastrin level (maximum of 3000 and 7000 pg/mL, respectively) were reported .…”

Medical Therapy of Gastroesophageal Reflux Disease Beyond Proton Pump Inhibitors: Where Are We Heading

“…Treatment options for this condition are still pending. omized studies, vonoprazan was equally effective both in terms of healing of erosive esophagitis and improvement of symptoms [8], and in patients with PPI-refractory GERD vonoprazan demonstrated efficacy in a substantial number of cases [6,9].…”

“…Among several P-CABs, vonoprazan has evolved as the most intensively studied compound. Depending on the dose administered, more profound acid inhibition and longer duration can be achieved [5] which is also reflected by exaggerated gastrin increases compared to PPI [6,7]. In rand-…”

New Minimally Invasive Endoscopic and Surgical Therapies for Gastroesophageal Reflux Disease (GERD)

“…Recently, those refractory to PPIs respond to vanoprazan, a "potassium-competitive acid blocker" that has a much stronger inhibitory effect on acid secretion from gastric parietal cells. Baclofen is also efficient in reducing transient relaxation of the LES, a "GABA-B agonist", which unfortunately also has side effects, reason for which it is not approved by the FDA (11,12).…”