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Vonoprazan Reduces Nighttime Heartburn in NERD Patients

Publication Title: Vonoprazan Improves Nocturnal Gastroesophageal Reflux Symptoms in Nonerosive Reflux Disease.

Summary

Question
This study investigated the effectiveness of vonoprazan, a potassium-competitive acid blocker (PCAB), in reducing nighttime symptoms of nonerosive reflux disease (NERD), a type of gastroesophageal reflux disease (GERD) where patients experience heartburn but lack visible damage to the esophagus. The authors specifically evaluated its impact on nocturnal heartburn using a validated questionnaire and electronic diary entries.
Why it Matters

GERD affects over 30% of adults in the U.S., with nocturnal symptoms reported by nearly 80% of patients. These nighttime symptoms often disrupt sleep, impair quality of life, and increase the risk of complications.

Methods
The researchers conducted a randomized, double-blind, placebo-controlled study at 91 U.S. centers. Participants included 772 adults experiencing heartburn at least four days per week but without visible esophageal damage. Subjects were assigned to either placebo, vonoprazan 10 mg, or vonoprazan 20 mg daily for four weeks. Those initially on placebo were reassigned to vonoprazan for an additional 20 weeks, while others continued their original dose. Nighttime heartburn was tracked through electronic diaries and the Nocturnal Gastroesophageal Reflux Disease Symptom Severity and Impact Questionnaire (N-GSSIQ).
Key Findings

Vonoprazan increased the percentage of heartburn-free nights compared to placebo, with rates of 59.9% for the 10 mg dose and 56.4% for the 20 mg dose versus 43.3% for placebo. It also improved N-GSSIQ scores, indicating reduced symptom severity, less concern about GERD, and sustained relief over six months. The treatment effect was rapid, with sepration between vonoprazan and placebo after the first dose.

Implications

The findings suggest that vonoprazan offers an effective option for managing nocturnal GERD symptoms, which also could enhance sleep quality.

Next Steps

Comparative studies against PPIs will be important to clarify vonoprazan's relative benefits in managing nocturnal GERD symptoms.

Funding Information
This research was supported by Phathom Pharmaceuticals. Yale University also provided funding and support for this research.

Full Citation

Antunes C, Ghosh G, Katz P, Yadlapati R, Leifke E, Harris T, Graham H, Laine L. Vonoprazan Improves Nocturnal Gastroesophageal Reflux Symptoms in Nonerosive Reflux Disease. The American Journal Of Gastroenterology 2025 PMID: 41081570, DOI: 10.14309/ajg.0000000000003794.
This AI-assisted summary has been reviewed and approved by at least one of the study's authors to ensure it accurately reflects the research.

Authors

  • Catiele Antunes, MD

    First Author
    Yale School of Medicine

    Assistant Professor of Medicine (Digestive Diseases)

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  • Loren Laine, MD

    Last Author
    Yale School of Medicine

    Professor of Medicine (Digestive Diseases)

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Other Authors

  • Gaurav Ghosh;
  • Philip Katz;
  • Rena Yadlapati;
  • Eckhard Leifke;
  • Tom Harris;
  • Hillary Graham

Research Themes

Concepts