Nighttime Acid Reflux in Gastroesophageal Reflux Disease -Is It a Problem That Can Be Solved?

The article addresses nighttime acid reflux in gastroesophageal reflux disease (GERD), a common problem that impairs sleep quality and may increase the risk of cardiovascular disease, esophageal adenocarcinoma, and obstructive sleep apnea. Proton pump inhibitors (PPIs) can improve nocturnal symptoms but often provide incomplete acid suppression due to slow onset and short half-life. Potassium-competitive acid blockers (P-CABs), such as tegoprazan, have a faster onset and longer duration. The editorial discusses whether nighttime reflux can be better managed with P-CABs compared to PPIs, focusing on a randomized controlled trial comparing tegoprazan with esomeprazole for nocturnal symptoms and sleep disturbances in GERD.

Prior work shows nighttime heartburn is underappreciated yet impacts sleep and daytime function (Shaker et al., 2003). Daytime sleepiness is linked to higher mortality and cardiovascular disease (Newman et al., 2000). Symptomatic GERD is a risk factor for esophageal adenocarcinoma (Lagergren et al., 1999). The relationship between GERD and sleep is complex (Kurin et al., 2021). While PPIs can help, nocturnal acid control may be incomplete; strategies such as adding nighttime H2 receptor antagonists have shown benefit (Rackoff et al., 2005), and pharmacokinetic data highlight limits of PPI acid suppression (Katz et al., 2004). Consensus guidance recommends P-CABs as an initial option for GERD with comparable efficacy to PPIs (Jung et al., 2021). Tegoprazan has demonstrated efficacy in non-erosive reflux disease and symptom improvement (Kim SH et al., 2021) and provides sustained night-time acid suppression compared with vonoprazan or esomeprazole in healthy subjects (Yang et al., 2022).

The editorial summarizes a multicenter, double-blind randomized controlled trial by Kim et al. involving 46 patients with erosive esophagitis and GERD-related nocturnal symptoms. Participants were randomly assigned to tegoprazan 50 mg or esomeprazole 40 mg. Outcomes included time to first nighttime heartburn-free interval, percentage of nighttime heartburn-free days, and changes in symptom scores (Korean Gastrointestinal Symptom Rating Scale and the Korean version of the Epworth Sleepiness Scale). The study was designed as a pilot to inform larger trials.

Compared with esomeprazole, tegoprazan led to approximately half the time to achieve the first nighttime heartburn-free interval and a higher percentage of nighttime heartburn-free days. Improvements in symptom scores (Korean GSRS and Korean Epworth Sleepiness Scale) were more pronounced in the tegoprazan group, though differences between groups were not statistically significant in this pilot study. The authors estimated that enrolling 60 or more patients per group might demonstrate statistically significant differences.

Findings suggest that tegoprazan’s rapid onset and effective acid suppression may provide faster relief of nocturnal GERD symptoms compared with PPIs. Although statistical significance was not reached due to small sample size, the direction and magnitude of effects support the hypothesis that P-CABs could better address nighttime symptoms. This work is notable as the first study directly comparing tegoprazan with a PPI for nocturnal symptom control (beyond acid suppression data in healthy subjects). Improved nighttime control has important implications for sleep quality, daytime functioning, and potentially long-term health risks associated with nocturnal reflux.

Tegoprazan appears to be a promising option for managing nighttime reflux symptoms, potentially offering advantages over PPIs due to faster onset and sustained acid suppression. While this pilot trial suggests benefit, larger, adequately powered randomized trials are needed to confirm efficacy on nocturnal symptoms and sleep outcomes and to inform clinical practice.

The summarized trial was a pilot with a small sample size (n=46), limiting statistical power. Formal sample size calculation was challenging due to limited prior data. Between-group differences did not reach statistical significance; estimates indicate that 60 or more patients per arm may be needed. Generalizability is constrained by the pilot nature and inclusion of patients with erosive esophagitis and nocturnal symptoms.