Triple Therapy-Based on Tegoprazan, a New Potassium-Competitive Acid Blocker, for First-Line Treatment of Helicobacter pylori Infection: A Randomized, Double-Blind, Phase III, Clinical Trial

Abstract

Background/aims: We examined the efficacy and safety of tegoprazan as a part of first-line triple therapy for Helicobacter pylori eradication.

Methods: A randomized, double-blind, controlled, multicenter study was performed to evaluate whether tegoprazan (50 mg)-based triple therapy (TPZ) was noninferior to lansoprazole (30 mg)- based triple therapy (LPZ) (with amoxicillin 1 g and clarithromycin 500 mg; all administered twice daily for 7 days) for treating H. pylori. The primary endpoint was the H. pylori eradication rate. Subgroup analyses were performed according to the cytochrome P450 (CYP) 2C19 genotype, the minimum inhibitory concentration (MIC) of amoxicillin and clarithromycin, and underlying gastric diseases.

Results: In total, 350 H. pylori-positive patients were randomly allocated to the TPZ or LPZ group. The H. pylori eradication rates in the TPZ and LPZ groups were 62.86% (110/175) and 60.57% (106/175) in an intention-to-treat analysis and 69.33% (104/150) and 67.33% (101/150) in a per-protocol analysis (non-inferiority test, p=0.009 and p=0.013), respectively. Subgroup analyses according to MICs or CYP2C19 did not show remarkable differences in eradication rate. Both first-line triple therapies were well-tolerated with no notable differences.

Conclusions: TPZ is as effective as proton pump inhibitor-based triple therapy and is as safe as first-line H. pylori eradication therapy but does not overcome the clarithromycin resistance of H. pylori in Korea (ClinicalTrials.gov identifier NCT03317223).

Keywords: Helicobacter pylori; Potassium-competitive acid blocker; Tegoprazan.

Conflict of interest statement

CONFLICTS OF INTEREST

This study was funded in full by HK inno.N Corp., Seoul, South Korea. HK inno.N Corp. contributed to the study design, data management, statistical analysis, and approval of publication in co-operation with all the authors. Y.C.L., B.W.K., and J.H.K. are editorial board members of the journal but were not involved in the peer reviewer selection, evaluation, or decision process of this article. No other potential conflicts of interest relevant to this article were reported.

Figures

Fig. 1

Schematic diagram showing the study design. TPZ, tegoprazan-based triple therapy; LPZ, lansoprazole-based triple therapy.

Fig. 2

CONSORT flow diagram. From the tegoprazan-based triple therapy (TPZ) and lansoprazole-based triple therapy (LPZ) groups, 161 and 160 participants, respectively, completed the eradication therapy.

Fig. 3

Helicobacterpylori eradication rates with first-line triple therapy in an intention-to treat (A), full analysis (B), and per-protocol set (C). The p-values for non-inferiority tests are provided. TPZ, tegoprazan-based triple therapy; LPZ, lansoprazole-based triple therapy. *Statistically significant.

Fig. 4

Helicobacterpylori eradication rates according to underlying gastric disease (A), MICs of antibiotics (B, C), age (D), and sex (E). TPZ, tegoprazan-based triple therapy group; LPZ, lansoprazole-based triple therapy group; PUD, peptic ulcer disease; CAG, chronic gastritis; NS, not significant; MIC, minimum inhibitory concentration; CLR, clarithromycin; AMX, amoxicillin.

Fig. 5

Distribution of the minimum inhibitory concentration (MIC) of clarithromycin (A) and amoxicillin (B), determined using the Helicobacterpylori isolates obtained from study participants. The dotted line indicates the break point for each antibiotic. The breakpoints for clarithromycin and amoxicillin were 0.5 μg/mL and 0.125 μg/mL, respectively; however, they are placed a little to the right of the breakpoint, for readability. The majority of isolates (dotted arrow) resistant to clarithromycin had MIC values ranging from 8 to 128 μg/mL. LPZ, lansoprazole-based triple therapy; TPZ, tegoprazan-based triple therapy.