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Randomised clinical trial: efficacy and safety of vonoprazan vs. lansoprazole in patients with gastric or duodenal ulcers - results from two phase 3, non-inferiority randomised controlled trials.

ABSTRACT: BACKGROUND:Vonoprazan is a new potassium-competitive acid blocker for treatment of acid-related diseases. AIM:To conduct two randomised-controlled trials, to evaluate the non-inferiority of vonoprazan vs. lansoprazole, a proton pump inhibitor, for treatment of gastric ulcer (GU) or duodenal ulcer (DU). METHODS:Patients aged ?20 years with ?1 endoscopically-confirmed GU or DU (?5 mm white coating) were randomised 1:1 using double-dummy blinding to receive lansoprazole (30 mg) or vonoprazan (20 mg) for 8 (GU study) or 6 (DU study) weeks. The primary endpoint was the proportion of patients with endoscopically confirmed healed GU or DU. RESULTS:For GU, 93.5% (216/231) of vonoprazan-treated patients and 93.8% (211/225) of lansoprazole-treated patients achieved healed GU; non-inferiority of vonoprazan to lansoprazole was confirmed [difference = -0.3% (95% CI -4.750, 4.208); P = 0.0011]. For DU, 95.5% (170/178) of vonoprazan-treated patients and 98.3% (177/180) of lansoprazole-treated patients achieved healed DU; non-inferiority to lansoprazole was not confirmed [difference = -2.8% (95% CI -6.400, 0.745); P = 0.0654]. The incidences of treatment-emergent adverse events were slightly lower for GU and slightly higher for DU with vonoprazan than with lansoprazole. There was one death (subarachnoid haemorrhage) in the vonoprazan group (DU). The possibility of a relationship between this unexpected patient death and the study drug could not be ruled out. In both studies, increases in serum gastrin levels were greater in vonoprazan-treated vs. lansoprazole-treated patients; levels returned to baseline after treatment in both groups. CONCLUSIONS:Vonoprazan 20 mg has a similar tolerability profile to lansoprazole 30 mg and is non-inferior with respect to GU healing and has similar efficacy for DU healing.

SUBMITTER: Miwa H

PROVIDER: S-EPMC6680291 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Randomised clinical trial: efficacy and safety of vonoprazan vs. lansoprazole in patients with gastric or duodenal ulcers - results from two phase 3, non-inferiority randomised controlled trials.

Miwa H H Uedo N N Watari J J Mori Y Y Sakurai Y Y Takanami Y Y Nishimura A A Tatsumi T T Sakaki N N

Alimentary pharmacology & therapeutics 20161127 2

<h4>Background</h4>Vonoprazan is a new potassium-competitive acid blocker for treatment of acid-related diseases.<h4>Aim</h4>To conduct two randomised-controlled trials, to evaluate the non-inferiority of vonoprazan vs. lansoprazole, a proton pump inhibitor, for treatment of gastric ulcer (GU) or duodenal ulcer (DU).<h4>Methods</h4>Patients aged ≥20 years with ≥1 endoscopically-confirmed GU or DU (≥5 mm white coating) were randomised 1:1 using double-dummy blinding to receive lansoprazole (30 mg ...[more]

PMID: 27891632

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Project description:BackgroundThe pharmacokinetic and clinical behaviors of many proton pump inhibitors (PPIs) in peptic ulcer treatment are altered by CYP2C19 genetic polymorphisms. This non-inferiority study evaluated the efficacy and safety of the novel PPI anaprazole compared with rabeprazole. We also explored the influence of Helicobacter pylori ( H. pylori ) infection status and CYP2C19 polymorphism on anaprazole.MethodsIn this multicenter, randomized, double-blind, double-dummy, positive-drug parallel-controlled, phase III study, Chinese patients with duodenal ulcers were randomized 1:1 to receive rabeprazole 10 mg + anaprazole placebo or rabeprazole placebo + anaprazole 20 mg once daily for 4 weeks. The primary efficacy endpoint was the 4-week ulcer healing rate assessed by blinded independent review. Secondary endpoints were the proportion of patients with improved overall and individual duodenal ulcer symptoms at 4 weeks. Furthermore, exploratory subgroup analysis of the primary endpoint by H. pylori status and CYP2C19 polymorphism was conducted. Adverse events were monitored for safety. Non-inferiority analysis was conducted for the primary endpoint.ResultsThe study enrolled 448 patients (anaprazole, n = 225; rabeprazole, n = 223). The 4-week healing rates were 90.9% and 93.7% for anaprazole and rabeprazole, respectively (difference, -2.8% [95% confidence interval, -7.7%, 2.2%]), demonstrating non-inferiority of anaprazole to rabeprazole. Overall duodenal ulcer symptoms improved in 90.9% and 92.5% of patients, respectively. Improvement rates of individual symptoms were similar between the groups. Healing rates did not significantly differ by H. pylori status or CYP2C19 genotype for either treatment group. The incidence of treatment-emergent adverse events was similar for anaprazole (72/220, 32.7%) and rabeprazole (84/219, 38.4%).ConclusionsThe efficacy of anaprazole is non-inferior to that of rabeprazole in Chinese patients with duodenal ulcers.RegistrationClinicalTrials.gov, NCT04215653.

Project description:BACKGROUND:Vonoprazan is a potassium-competitive acid blocker (P-CAB) that is frequently used in Japan for Helicobacter pylori (H. pylori) eradication, treatment of gastroesophageal reflux disease, and treatment of post endoscopic submucosal dissection (ESD) complications. We sought to determine if vonoprazan was superior to proton pump inhibitors (PPIs) for treating ESD-induced ulcers (as assessed by ulcer healing and shrinkage ratios) and preventing delayed bleeding over various treatment durations (2, 4, and 8 weeks). METHODS:We collected randomized controlled trials (RCTs) and observational studies that discussed the effectiveness of vonoprazan and PPIs on ESD-induced ulcers and bleeding from PubMed, Cochrane Library, ClinicalTrials.gov, and Google Scholar. Studies were selected according to pre-established eligibility criteria and data were extracted separately by 2 researchers with double-check. We used the Cochrane risk of bias tool to assess RCTs and the Newcastle-Ottawa Quality Assessment Scale to assess observational studies. Meta-analyses, based on the random-effects model, were conducted to compare differences in ulcer shrinkage ratios (%) and odds ratios (ORs) for ulcer healing and delayed bleeding. Publication bias was evaluated using funnel plots and Egger regression test. Heterogeneity was assessed using I statistics. A sensitivity analysis was conducted to check the robustness of results. The evidential quality of the findings was assessed using the GRADE profiler. RESULTS:Thirteen studies were included in this meta-analysis. The OR effect sizes of vonoprazan relative to PPIs for ulcer healing were 1.33 (P = .13) with a 95% CI (0.33-3.21) at 4 weeks and 1.48 (P = .09) with a 95% CI (0.81-5.20) at 8 weeks. The overall effect size for the shrinkage ratio was 12.24% (P = .16) with a 95% CI (-4.96-29.44) at 2 weeks. The effect size of its subgroup of H. pylori-positive patients was 19.51% (P < .001) with a 95% CI (11.91-27.12). The overall OR for the occurrence of delayed bleeding was 0.66 (P = .26) with a 95% CI (0.32-1.35). After excluding combination drug studies, the overall ORs between vonoprazan and PPIs on ulcer healing and delayed bleeding were 1.44 and 0.76, respectively. CONCLUSION:During the first 2 weeks of treatment, vonoprazan was more effective than PPIs for treating H. pylori-positive patients with ESD-induced gastric ulcers.

Project description:AimTo compare vonoprazan 10 and 20 mg vs lansoprazole 15 mg as maintenance therapy in healed erosive esophagitis (EE).MethodsA total of 607 patients aged ≥ 20 years, with endoscopically-confirmed healed EE following 8 wk of treatment with vonoprazan 20 mg once daily, were randomized 1:1:1 to receive lansoprazole 15 mg (n = 201), vonoprazan 10 mg (n = 202), or vonoprazan 20 mg (n = 204), once daily. The primary endpoint of the study was the rate of endoscopically-confirmed EE recurrence during a 24-wk maintenance period. The secondary endpoint was the EE recurrence rate at Week 12 during maintenance treatment. Additional efficacy endpoints included the incidence of heartburn and acid reflux, and the EE healing rate 4 wk after the initiation of maintenance treatment. Safety endpoints comprised adverse events (AEs), vital signs, electrocardiogram findings, clinical laboratory results, serum gastrin and pepsinogen I/II levels, and gastric mucosa histopathology results.ResultsRates of EE recurrence during the 24-wk maintenance period were 16.8%, 5.1%, and 2.0% with lansoprazole 15 mg, vonoprazan 10 mg, and vonoprazan 20 mg, respectively. Vonoprazan was shown to be non-inferior to lansoprazole 15 mg (P < 0.0001 for both doses). In a post-hoc analysis, EE recurrence at Week 24 was significantly reduced with vonoprazan at both the 10 mg and the 20 mg dose vs lansoprazole 15 mg (5.1% vs 16.8%, P = 0.0002, and 2.0% vs 16.8%, P < 0.0001, respectively); by contrast, the EE recurrence rate did not differ significantly between the two doses of vonoprazan (P = 0.1090). The safety profiles of vonoprazan 10 and 20 mg were similar to that of lansoprazole 15 mg in patients with healed EE. Treatment-related AEs were reported in 11.4%, 10.4%, and 10.3% of patients in the lansoprazole 15 mg, vonoprazan 10 mg, and vonoprazan 20 mg arms, respectively.ConclusionOur findings confirm the non-inferiority of vonoprazan 10 and 20 mg to lansoprazole 15 mg as maintenance therapy for patients with healed EE.

Project description:Background: Proton pump inhibitors (PPIs) are validated gastric acid suppressors and have been widely used to treat patients with active duodenal ulcers. Although existing PPIs have shown great efficacy, many scientists are still devoted to developing more effective PPIs with better safety profile. Herein, we aimed to compare the safety and efficacy of anaprazole in duodenal mucosal healing, a novel PPI, to that of rabeprazole. Methods: In this multicenter, randomized, positive-controlled, double-blinded, parallel-group phase II clinical trial, a total of 150 qualified patients with endoscopically confirmed active duodenal ulcers were randomized (1:1:1) to receive rabeprazole 10 mg, anaprazole 20 mg or anaprazole 40 mg for 4 weeks. The ulcer healing rates after 4 weeks of treatment were compared between groups by independent central review and investigator review. In addition, symptoms and safety were evaluated. Results: Based on the independent central review, the ulcer healing rates of the 10 mg rabeprazole, 20 mg anaprazole and 40 mg anaprazole groups were 88.0, 85.1, and 87.5%, respectively, in the FAS population and 88.9, 86.0, and 90.9%, respectively, in the PPS population. The ulcer healing rate difference between anaprazole 20 mg and Rabeprazole 10 mg is -2.9% (95% CI, -16.5-10.7%), and -0.5% (95% CI, -13.5-12.5%) between anaprazole 40 mg and Rabeprazole 10 mg, in the FAS population. Based on the investigator review, the ulcer healing rates of the 10 mg rabeprazole, 20 mg anaprazole, and 40 mg anaprazole groups were 72.0, 70.2, and 77.1%, respectively, in the FAS population and 75.6, 72.1, and 79.5%, respectively, in the PPS population. The ulcer healing rate difference between anaprazole 20 mg and Rabeprazole 10 mg is -1.8% (95% CI, -19.8-16.3%), and 5.1% (95% CI, -12.2-22.3%) between anaprazole 40 mg and Rabeprazole 10 mg, in the FAS population. Most patients (>90%) eventually achieved complete symptom relief. The incidence rates of adverse events were of no significant differences among the treatment groups. Potential possible better liver tolerance was observed in two anaprazole dose groups than rabeprazole 10 mg group. Conclusion: Both at a dosage of 20 and 40 mg daily, anaprazole, is effective with good safety profile in the treatment of active duodenal ulcers in this Phase 2 study, which allows anaprazole to be advanced to a phase III clinical trial. Clinical Trial Registration: https://www.clinicaltrials.gov/ct2/results?cond=&term=NCT04503629&cntry=&state=&city=&dist=, Identifier: CTR20181464, NCT04503629.

Dataset Information

Randomised clinical trial: efficacy and safety of vonoprazan vs. lansoprazole in patients with gastric or duodenal ulcers - results from two phase 3, non-inferiority randomised controlled trials.

Publications

Randomised clinical trial: efficacy and safety of vonoprazan vs. lansoprazole in patients with gastric or duodenal ulcers - results from two phase 3, non-inferiority randomised controlled trials.

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