In the treatment of Helicobacter pylori infection, combination therapies using the oral potassium-competitive acid blocker vonoprazan were superior to standard proton pump inhibitor (PPI)–based triple therapy, producing higher eradication rates, according to combined data from a U.S. and a European phase 3 randomized, controlled trial.
Vonoprazan has been submitted to the Food and Drug Administration for approval with a Fast Track designation in combination with amoxicillin and clarithromycin (triple therapy) or amoxicillin alone (dual therapy) for treating H. pylori infection. It has already been approved in Japan for the treatment of gastric and duodenal ulcers, reflux esophagitis, secondary prevention of low-dose aspirin– or nonsteroidal anti-inflammatory drug–induced gastric mucosal damage, and for first and second-line H. pylori eradication therapy.
The study included 1,046 treatment-naive patients who had dyspepsia, a recent or new diagnosis of a nonbleeding peptic ulcer, a history of a peptic ulcer, or long-term stable use of an NSAID. Patients were randomized to PPI-based triple therapy (lansoprazole, amoxicillin, clarithromycin), vonoprazan triple therapy (plus amoxicillin, clarithromycin), or vonoprazan dual therapy (amoxicillin). The treatment period was 14 days, followed by 13C urea breath test (UBT) 4 weeks after treatment.
The researchers conducted several analyses, including: Modified intention-to-treat analyses, which included all enrollees; per protocol analyses, which included patients who took at least 75% of each study medication and underwent 13C UBT in the expected time frame; and a safety population of all patients who took at least one study drug.
Among patients with H. pylori strains that were not resistant to clarithromycin, the PPI-based triple-therapy group had an eradication rate of 78.8%, compared with 84.7% in the vonoprazan triple-therapy group (P < .0001), and 78.5% in the vonoprazan dual-therapy group (P = .0037). In the per protocol analysis, PPI-based triple therapy eradicated H. pylori 82.1% of the time, compared with 90.4% in the vonoprazan triple-therapy group (P < .0001) and 81.2% in the vonoprazan dual-therapy group (P = .0077). Both vonoprazan treatment groups were noninferior to PPI-based triple therapy.
A prespecified exploratory analysis found that vonoprazan triple therapy outperformed PPI-based triple therapy in the modified intention-to-treat population (P = .0408) and the per protocol population (P = .0059).
Among patients with clarithromycin-resistant strains of H. pylori, in the modified intention-to-treat population, 31.9% achieved eradication with PPI triple therapy, compared with 65.8% in the vonoprazan triple-therapy group, and 69.6% in the vonoprazan dual-therapy group. In the per protocol population, the numbers were 29.0% versus 67.2% and 79.5%, respectively (P < .0001 for both versus PPI triple therapy).
Among all patients, in the modified intention-to-treat population, 68.5% achieved eradication with PPI triple therapy, 80.5% with vonoprazan triple therapy (P =. 0001), and 77.2% with vonoprazan dual therapy (P = .0063). In the per protocol population, the numbers were 70.0%, 85.7% (P < .0001), and 81.1% (P = .0013), respectively.
Safety outcomes were similar among the three groups, with treatment-emergent adverse events occurring in 34.5% of the PPI triple-therapy group (1.2% discontinued), 34.1% of the vonoprazan triple-therapy group (2.3% discontinued), and 29.9% in the vonoprazan dual-therapy group (0.9% discontinued).