C Antunes et al. Am J Gastroenterol 2026; 121:1866-1874. Open Access! Vonoprazan Improves Nocturnal Gastroesophageal Reflux Symptoms in Nonerosive Reflux Disease Thanks to Ben Gold for sharing this study.

Methods: This was a prospective, randomized, double-blind, placebo-controlled phase 3 study conducted at 91 centers across the United States. Adults (n=772) 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.

Key findings:

• Median percentages of heartburn-free nights during the 4-week placebo-controlled treatment period were 45.5% for placebo, 70.4% for vonoprazan 10 mg, and 71.0% for vonoprazan 20 mg.

Discussion Points:

• “In the few randomized controlled trials available which evaluated the effect of PPIs on nocturnal symptoms, the mean and median rates of heartburn-free nights with different therapies, as well as the placebo response, were similar to what we observed in our study (17–19)…Many of the PPI studies assessing therapies for nocturnal symptoms are limited because of their short follow-up duration, often limited to 2–4 weeks.”
• Strengths of study: This was a “large multicenter study, placebo-controlled, with a diverse PPI-experienced patient population who presented with reflux symptoms occurring at baseline on approximately 75% of nights.”
• Limitation: “A limitation of our study, and many previous studies of NERD, is the lack of positive pH testing to document acid reflux as the cause of symptoms. hus, some subjects likely had conditions other than reflux (e.g., functional heartburn) as a cause of their symptoms, which may reduce the overall response rates seen with acid suppression.”
• “The response rates for nighttime heartburn with vonoprazan were not substantially different between patients who reported previous response to PPIs and those who did not, suggesting that previous PPI response may not be a predictor of response to treatment with vonoprazan. However, this observation was based on a post hoc analysis.”

My take (borrowed from the authors): “Vonoprazan had a rapid effect on nighttime heartburn symptoms which was sustained through 24 weeks.”

Related blog posts:

• Vonoprazan Treatment of Heartburn in Randomized Study of Patients with Non-Erosive Reflux Disease
• VISION 5-Year Study Results: Safety of Vonoprazan in Erosive Esophagitis
• Is Vonoprazan Better Than Intravenous PPIs for High-Risk Peptic Ulcers?
• Improved Efficacy with Vonoprazan for Severe Esophagitis
• Why Vonoprazan Is More Effective For Erosive Esophagitis Than a Proton Pump Inhibitor
• Vonoprazan-Tetracycline: Effective Dual Rescue Regimen for H Pylori