INTRODUCTION: This analysis of a phase 3 randomized trial evaluated the efficacy of vonoprazan on pre-specified endpoints for night-time symptoms in patients with non-erosive reflux disease. METHODS: Adults with heartburn ≥4 days/week and without erosive esophagitis, were randomized to placebo, vonoprazan 10mg, or vonoprazan 20mg. After 4 weeks, subjects on placebo were re-randomized to vonoprazan 10mg or 20mg, and those already on vonoprazan continued the same dose for an additional 20 weeks. N-GSSIQ, a validated instrument for nocturnal gastroesophageal reflux disease (GERD) 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 10mg (least square (LS) mean difference=16.5%, p<0.0001) and 56.4% for vonoprazan 20mg (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 10mg and 20mg, respectively; p<0.005 for both comparisons), nocturnal symptom severity subscale (LS mean difference vs. placebo of -5.4 and -3.5 for vonoprazan 10mg and 20mg; p<0.001 for both comparisons), and concern about nocturnal GERD subscale (LS mean difference vs. placebo of -2.0 for both vonoprazan 10mg and 20mg; 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.
