INTRODUCTION: This analysis of a phase 3 randomized trial evaluated the efficacy of vonoprazan on prespecified end points for nighttime symptoms in patients with nonerosive reflux disease. METHODS: Adults with heartburn ≥4 d/wk and without erosive esophagitis were randomized to placebo, vonoprazan 10 mg, or vonoprazan 20 mg. After 4 weeks, subjects on placebo were rerandomized to vonoprazan 10 or 20 mg, and those already on vonoprazan continued the same dose for an additional 20 weeks. Nocturnal Gastro-esophageal Reflux Disease Symptom Severity and Impact Questionnaire (N-GSSIQ), a validated instrument for nocturnal gastroesophageal reflux disease, was completed at baseline and weeks 4, 12, and 24. Minimal important differences for N-GSSIQ total score and subscales were defined as ≥0.4. RESULTS: Among 772 subjects, the mean percentage of heartburn-free nights at week 4 was 43.3% for placebo vs 59.9% for vonoprazan 10 mg (least squares [LS] mean difference = 16.5%, P < 0.0001) and 56.4% for vonoprazan 20 mg (LS mean difference, 13.1%, P < 0.0001). Vonoprazan improved N-GSSIQ total score (LS mean difference vs placebo of -2.9 and -1.8 for vonoprazan 10 and 20 mg, respectively; P < 0.005 for both comparisons), nocturnal symptom severity subscale (LS mean difference vs placebo of -5.4 and -3.5 for vonoprazan 10 and 20 mg; P < 0.001 for both comparisons), and concern about nocturnal gastroesophageal reflux disease subscale (LS mean difference vs placebo of -2.0 for both vonoprazan 10 and 20 mg; P < 0.0001). The benefit on heartburn-free nights and N-GSSIQ scores was observed through the additional 20 weeks. DISCUSSION: Our study suggests that vonoprazan leads to relief of nighttime heartburn in patients with heartburn and a normal endoscopy.
