Nighttime heartburn, a common symptom of gastroesophageal reflux disease (GERD), significantly impacts sleep quality and overall well-being. It's linked to increased risks of cardiovascular disease, esophageal adenocarcinoma, and obstructive sleep apnea. While proton pump inhibitors (PPIs) offer some relief, their slow onset and short half-life limit their effectiveness for nocturnal symptoms. Potassium-competitive acid blockers (P-CABs), such as tegoprazan, offer a potential advantage with their rapid onset and longer duration of action. This editorial focuses on a study comparing the efficacy of tegoprazan to esomeprazole (a PPI) in managing nighttime heartburn and improving sleep quality in patients with GERD. The study's hypothesis was that tegoprazan's rapid action would lead to faster nighttime symptom improvement compared to esomeprazole. The importance of this research lies in finding effective treatments to alleviate nocturnal GERD symptoms, thereby improving patient quality of life and potentially reducing the risk of associated comorbidities. This is particularly critical given the under-appreciation of nighttime heartburn as a clinical problem affecting sleep and daytime function, as highlighted in previous research.

Existing literature demonstrates the significant negative impact of nighttime acid reflux on sleep quality and daily functioning. Studies have shown associations between nighttime heartburn and various health problems, including cardiovascular disease, esophageal adenocarcinoma, and obstructive sleep apnea. PPIs have been used to treat these symptoms, but their limitations regarding slow onset and short half-life have led to the exploration of alternative treatments. P-CABs, with their faster onset of action and longer duration of effect, have emerged as promising alternatives to PPIs for GERD management. Previous research has established the effectiveness of tegoprazan in improving GERD symptoms, including daytime heartburn and erosions. However, limited data existed on its efficacy specifically for nighttime symptoms before the study discussed in this editorial.

Kim et al.'s study was a multicenter, double-blind, randomized controlled trial comparing tegoprazan 50 mg to esomeprazole 40 mg in 46 patients with erosive esophagitis and GERD-related nocturnal symptoms. Patients were randomly assigned to one of the treatment groups. The primary outcome measures were time to the first nighttime heartburn-free interval and the percentage of nighttime heartburn-free days. Secondary outcome measures included improvements in symptom scores using the Korean Gastrointestinal Symptom Rating Scale and the Korean version of the Epworth Sleepiness Scale. The study's methodology involved a rigorous double-blind design to minimize bias, with patients and researchers unaware of treatment allocation until the end of the study. This design enhances the reliability and objectivity of the results. The use of validated symptom scales adds to the study's strength by providing standardized measures of symptom severity and sleep quality. While the sample size was relatively small (46 patients), the authors acknowledge this limitation and suggest that a larger sample size is needed to confirm the statistical significance of their findings. This pilot study served as a basis for future large-scale studies.

The study revealed that the time to the first nighttime heartburn-free interval was approximately half as long in the tegoprazan group compared to the esomeprazole group. The percentage of nighttime heartburn-free days was also significantly higher in the tegoprazan group. Although the differences in symptom scores (Korean Gastrointestinal Symptom Rating Scale and Korean version of the Epworth Sleepiness Scale) between the two groups were not statistically significant, the improvements were more pronounced in the tegoprazan group. The authors suggest that a larger study with approximately 60 or more patients in each group would be needed to achieve statistical significance for these secondary outcomes. The study's findings demonstrate a clear trend toward superior efficacy of tegoprazan over esomeprazole in achieving quicker relief from nighttime heartburn, supporting the hypothesis that the rapid onset of action of tegoprazan is beneficial for patients experiencing nighttime GERD symptoms. This finding is supported by other research indicating sustained nighttime acid suppression with tegoprazan in healthy subjects.

This study's findings contribute significantly to our understanding of managing nocturnal GERD symptoms. The faster onset of action of tegoprazan, as demonstrated by the shorter time to the first nighttime heartburn-free interval and higher percentage of heartburn-free nights, suggests a potential therapeutic advantage over esomeprazole. This improvement in nighttime symptom control may directly lead to enhanced sleep quality and overall better patient well-being. While the study didn't show statistically significant differences in overall symptom scores, the observed trend toward greater improvement in the tegoprazan group merits further investigation in larger trials. The results support the potential of tegoprazan as a valuable treatment option for patients with GERD who experience significant nighttime heartburn and sleep disturbances.

This pilot study suggests that tegoprazan may be a more effective treatment for nighttime GERD symptoms compared to esomeprazole due to its rapid onset of action. The findings warrant further investigation in larger-scale clinical trials to confirm these results and assess the long-term efficacy and safety of tegoprazan for the management of nocturnal GERD. Future research should focus on larger, more comprehensive studies to definitively establish the clinical benefit of tegoprazan for nighttime GERD symptoms and to evaluate its impact on long-term outcomes, including sleep quality and the prevention of GERD-related complications.

The small sample size of this study is a key limitation, potentially affecting the statistical power to detect significant differences between tegoprazan and esomeprazole for all outcome measures. The lack of statistically significant differences in some secondary outcome measures despite a trend towards improvement in the tegoprazan group also represents a limitation. Future research with a larger sample size is needed to definitively confirm the superiority of tegoprazan over esomeprazole for all aspects of nighttime GERD management.