Randomised clinical trial: Efficacy and safety of on‐demand vonoprazan versus placebo for non‐erosive reflux disease

Summary Background Non‐erosive reflux disease (NERD) symptoms are often episodic, making on‐demand treatment an attractive treatment approach. Aims We compared the efficacy and safety of on‐demand vonoprazan versus placebo in patients with NERD. Methods Patients with NERD, defined as heartburn for ≥6 months and for ≥4/7 consecutive days with normal endoscopy, received once‐daily vonoprazan 20 mg during a 4‐week run‐in period. Patients without heartburn during the last 7 days and with ≥80% study drug and diary compliance were randomised 1:1:1:1 to vonoprazan 10, 20, 40 mg or placebo on‐demand for 6 weeks. The primary endpoint was the percentage of evaluable heartburn episodes completely relieved within 3 h of on‐demand dosing and sustained for 24 h. Results Of 458 patients in the run‐in period, 207 entered the on‐demand period. In the vonoprazan 10 mg group, 56.0% (201/359) of evaluable heartburn episodes met the criteria for complete and sustained relief; 60.6% (198/327) in the 20 mg group; and 70.0% (226/323) in the 40 mg group, compared with 27.3% (101/370) in the placebo group ( p < 0.0001 versus placebo for each vonoprazan group). By 1 h post‐dose, vonoprazan was associated with complete relief of significantly more heartburn episodes compared with placebo. No serious treatment‐emergent adverse events were reported. Conclusion On‐demand vonoprazan may be a potential alternative to continued daily acid suppression therapy for the relief of episodic heartburn in patients with NERD. Clinicaltrials.gov : NCT04799158.