Vonoprazan, a novel potassium-competitive acid blocker, as a component of first-line and second-line triple therapy for Helicobacter pylori eradication: a phase III, randomised, double-blind study

Abstract

Objective: The objective of this study was to assess the efficacy, safety and tolerability of vonoprazan, a novel potassium-competitive acid blocker, as a component of Helicobacter pylori eradication therapy.

Design: A randomised, double-blind, multicentre, parallel-group study was conducted to verify the non-inferiority of vonoprazan 20 mg to lansoprazole 30 mg as part of first-line triple therapy (with amoxicillin 750 mg and clarithromycin 200 or 400 mg) in H pylori-positive patients with gastric or duodenal ulcer history. The first 50 patients failing first-line therapy with good compliance also received second-line vonoprazan-based triple therapy (with amoxicillin 750 mg and metronidazole 250 mg) as an open-label treatment.

Results: Of the 650 subjects randomly allocated to either first-line triple therapy, 641 subjects completed first-line therapy and 50 subjects completed second-line therapy. The first-line eradication rate (primary end point) was 92.6% (95% CI 89.2% to 95.2%) with vonoprazan versus 75.9% (95% CI 70.9% to 80.5%) with lansoprazole, with the difference being 16.7% (95% CI 11.2% to 22.1%) in favour of vonoprazan, thus confirming the non-inferiority of vonoprazan (p<0.0001). The second-line eradication rate (secondary end point) was also high (98.0%; 95% CI 89.4% to 99.9%) in those who received second-line therapy (n=50). Both first-line triple therapies were well tolerated with no notable differences. Second-line triple therapy was also well tolerated.

Conclusion: Vonoprazan is effective as part of first-line triple therapy and as part of second-line triple therapy in H pylori-positive patients with a history of gastric or duodenal ulcer.

Trial registration number: NCT01505127.

Keywords: ANTIBIOTIC THERAPY; CLINICAL TRIALS; HELICOBACTER PYLORI - TREATMENT; HELICOBACTER PYLORI INFECTION.

Figure 1

Flow diagram showing the study design. ^aAs part of triple therapy in combination with AMX and CLR. ^bAs part of triple therapy in combination with AMX and MTZ. AMX, amoxicillin; CLR, clarithromycin; LPZ, lansoprazole; MTZ, metronidazole; VPZ, vonoprazan.

Figure 2

CONSORT flow diagram showing progression through trial. AE, adverse event; CLR, clarithromycin; LPZ, lansoprazole; VPZ, vonoprazan.

Figure 3

Helicobacter pylori eradication rates (full analysis set) in (A) first-line triple therapy and (B) second-line triple therapy (95% CIs shown in brackets) are shown. ^aMissing urea breath test data (n=5); ^bmissing urea breath test data (n=1); p values for both non-inferiority and superiority tests are also provided. AMX, amoxicillin; CLR, clarithromycin; LPZ, lansoprazole; MTZ, metronidazole; VPZ, vonoprazan.

Figure 4

First-line Helicobacter pylori eradication rates in various subgroups (full analysis set) are shown. Six randomised subjects in whom the urea breath test had not been performed were excluded from these analyses; p values for superiority tests are provided. AMX, amoxicillin; CLR, clarithromycin; EM, extensive metabolisers; LPZ, lansoprazole; MIC, minimum inhibitory concentration; N.S., not significant; PM, poor metabolisers; VPZ, vonoprazan.