Therapeutic Efficacy of Vonoprazan versus Dexlansoprazole in the Treatment of Gastroesophageal Reflux Disease: A Randomized Controlled Trial

INTRODUCTION

Gastroesophageal reflux disease (GERD) is a prevalent condition marked by acid regurgitation and/or heartburn due to the reflux of gastric contents [1]. The clinical characteristics of the condition and its significant prevalence adversely affect the case's well-being and quality of life, while also placing a significant burden on healthcare systems regarding time and expenses [2].

Gastroesophageal reflux disease (GERD) is a prevalent gastrointestinal disorder, exhibiting a pooled prevalence of 21% in the United States (US) [3], resulting in over 4.6 million annual ambulatory care visits [4]. East Asian prevalence rates range from 2.5% to 7.8% [5]. A significant presentation of GERD is erosive esophagitis, affecting an estimated 25% to 50% of symptomatic patients [6].   

Esophageal dysmotility may be a contributing factor in GERD. Prior research indicates a higher prevalence of esophageal dysmotility in GERD patients experiencing globus sensation compared to those with typical GERD symptoms [8].

The primary objective of therapy for cases with gastroesophageal reflux disease is stomach acid suppression, with proton pump inhibitors (PPIs) that represent the current gold standard for diminishing gastric acidity, alleviating symptoms, and facilitating mucosal repair in cases with reflux esophagitis [9]. In patients receiving proton pump inhibitor therapy, esophageal mucosal healing demonstrates significantly greater predictability than symptomatic improvement [10].

Vonoprazan is known as a new family in the suppression of gastric acid, which is potassium competitive acid blockers [P-CABs]. Proton pump inhibitors (PPIs) exhibit several limitations affecting their therapeutic efficacy: ineffectiveness during periods of proton pump inactivity, such as nocturnal periods; variable efficacy influenced by genetic polymorphism, particularly within Asian populations; slow onset of action; short plasma half-life; and irreversible binding to the proton pump [11], but potassium competitive acid blockers (P-CABs) reversibly inhibit H+ and K+ ATPase, resulting in a great and long-term inhibition of acid secretion [12]. As reported in some studies, the healing rate of reflux esophagitis was superior to that of a PPI [dexlansoprazole], with a greater effect seen in cases with greater severity [13]. This research aims to conduct a head-to-head randomized controlled trial evaluating the comparative efficacy of Vonoprazan (P-CABs) and Dexlansoprazole (PPIs) in Egyptian patients diagnosed with gastroesophageal reflux disease.

PATIENTS AND METHODS

Study design:

This study was a randomized controlled, open-label trial conducted in the outpatient clinics of the Internal Medicine Department at Zagazig University Hospitals, extending from October 2024 to February 2025. The study included two groups, Group A received Vonoprazan twenty milligrams once daily, whereas Group B  received Dexlansoprazole sixty milligrams once daily for a duration of eight weeks. The Zagazig Institutional Review Board approved this study (IRB#: 745/5). It also was registered on https://clinicaltrials.gov/. Trial registration number: NCT06778395, Release Date: February 24, 2025.

Patient Selection and Data Collection:

Participants were selected from the ZUH internal medicine department using systematic random sampling. Inclusion criteria were: patients diagnosed with GERD (based on GERD scores and confirmed via upper GI endoscopy), aged 18 years or older, and of either sex.

Exclusion criteria included:

• Other GIT problems (Other esophageal disorders such as eosinophilic esophagitis and infectious esophagitis, scleroderma and esophageal stenosis, acute upper gastrointestinal hemorrhage, and gastric or duodenal ulcers, hypersecretion syndromes such as Zollinger Ellison syndrome).
• Other comorbidities (severe pulmonary, hepatic, renal, cardiovascular, neurological conditions, viral hepatitis or HIV, a history of cancer).
• Laboratory abnormalities (elevated serum glutamic oxaloacetic trans-aminase [SGOT] and glutamic pyruvic trans-aminase [SGPT] > 2.5 × the upper range in the limit of normal, elevated serum creatinine of more than 2 mg/dL.
• History of alcohol addiction, pregnancy and  breastfeeding.
• Medications were received within 4 weeks before the start of the study (PPIs, H2RAs, improvers of gastrointestinal motility, anticholinergics, prostaglandins, antacids, mucosal protectives, and H. pylori eradicators medications(.

Sample Size:

A sample size calculation, performed using OpenEpi Info with a 95% confidence interval, 80% power, and a 1:1 allocation ratio, yielded a minimum sample size of 48 patients (24 per group). This calculation was based on a projected 68.8% symptom relief rate for vonaprazan versus 25% for lansoprazole [14].

Eighty patients diagnosed with gastroesophageal reflux disease (GERD), based on GERD scores and upper GI endoscopy, were included in this study. These patients were categorized into two groups of 40, using computer-generated block randomization. Treatment group assignment (group A and group B) was performed in a 1:1 ratio via sealed envelope randomization using a dedicated website [15].

Clinical and laboratory examination:

A comprehensive assessment of all cases included sociodemographic data, detailed history, physical examination, and laboratory investigations (CBC, ESR, serum creatinine, serum urea, ALT, AST, serum albumin, serum bilirubin, PT, PTT, INR). GERD scores were obtained before treatment and at 1, 2, 4, and 8 weeks post-treatment initiation. Upper GI endoscopy was performed by experienced endoscopists at the ZUH endoscopic unit.

Assessment tools:

1. The gastroesophageal reflux disease questionnaire (GERD Q) is designed by Dent et al. [16]. In 2007, it was a self-administered diagnostic questionnaire consisting of six items. A score of 8 or more was highly suggested to be GERD. The 4-GERD Q score assesses the frequency of reflux and reflux-associated symptoms (RRAS) or treatment response via changes in the RRAS score; a score of 0 indicates no RRAS, while 12 represents the highest RRAS frequency. For the 4-GERD Q, a new cutoff score defines sufficient relief as ≤1 and complete resolution as 0 [17].
2. The FSSG score is a widely accepted metric for evaluating GERD symptoms [17,18]. The FSSG questionnaire, a 12-item instrument, assesses both acid reflux (7 items) and dysmotility-related symptoms (5 items). An FSSG score of 8 or greater suggests probable GERD, with higher scores correlating to more severe disease [19].
3. The Los Angeles classification system is subdivided into four classes [A-D] depending on the extent mucosal breaks through in cases of esophagitis. The Los Angeles Classification system uses esophagogastroduodenoscopy to categorize the severity of reflux esophagitis into four grades: Grade A, characterized by one or more esophageal mucosal breaks less than 5 mm in length; Grade B, exhibiting one or more mucosal breaks exceeding 5 mm but maintaining continuity across mucosal folds; Grade C, defined by continuous mucosal breaks spanning at least two mucosal folds, affecting less than 75% of the esophageal circumference; and Grade D, where mucosal breaks involve more than 75% of the esophageal circumference [20].

Intervention:

Groups A and B received once-daily doses of 20 mg Vonoprazan and 60 mg Dexlansoprazole, respectively, for eight weeks. To optimize therapeutic outcomes according to clinical guidelines, we utilized elevated dosages of Vonoprazan (20 mg OD) and Dexlansoprazole (60 mg OD); however, neither group reported adverse events during the study period. Throughout the study, patient medication adherence and the incidence of adverse effects were monitored via scheduled phone calls and outpatient clinic visits.

Outcomes Measures:

Primary Outcome Measure: Symptom relief assessed by the GERD-Q score.

 Secondary Outcome Measure: Focusing on symptom relief through using a frequency scale of the symptoms of gastroesophageal reflux disease questionnaire (FSSG) and mucosal healing by upper GI endoscopic evaluation.

Statistical analysis

Data was computerized and statistically analyzed using SPSS 27.0 for Windows [SPSS Inc., Chicago, IL, United States of America]. Qualitative data was expressed as frequency and percent Chi-square test [χ2] and Fisher exact have been utilized for independent data and McNemar Bowker test was used for paired data. The Shapiro-Wilk test was used for testing the normal distribution of quantitative data, mean and SD [standard deviation] were used in parametric data, and median in non-parametric data independent T-test and a Mann-Whitney test was utilized for independent data and Paired t and Wilcoxon test for paired data. If P-value ≤ 0.05 means a significant level, if p 0.05 indicates insignificant variance.

RESULTS

The study included eighty patients with GERD, who had attended the ZUH Internal Medicine Department, Table (1) reveals no statistically significant differences (p ≥ 0.05) among the two groups regarding age, BMI, sex, residence, clinical presentation, and red flag symptoms. Furthermore, no statistically significant differences were observed in laboratory data, with p-values for Hb, TLC, PLT, albumin, ALT, AST, serum creatinine, and BUN being 0.14, 0.09, 0.41, 0.19, 0.38, 0.44, 0.24, and 0.43, respectively.

Primary Outcomes:

 Table (2) demonstrates that no statistically significant difference exists between the study groups regarding GERD Q scores before treatment.  Group A (Vonoprazan) exhibited a mean ± SD of 15.92 ± 1.36, compared to 15.84 ± 1.61 in Group B (Dexlansoprazole), yielding a p-value of 0.81. Post-treatment, both groups showed significant improvement (99.42% in group A and 99.39% in group B), although the difference between the groups remained statistically insignificant (0.09 ± 0.23 in group A versus 0.10 ± 0.27 in group B, p-value = 0.65).  At one week, Vonoprazan (Group A) demonstrated 37.5% complete resolution and 62.5% sufficient relief, compared to Dexlansoprazole (Group B) at 50% and 50%, respectively (p=0.26).  At two weeks, Vonoprazan showed 50% complete resolution and 50% sufficient relief versus Dexlansoprazole at 52.5% and 47.5% (p=0.82). Four-week results indicated 62.5% complete resolution and 37.5% sufficient relief for Vonoprazan compared to 67.5% and 32.5% for Dexlansoprazole (p=0.64). Finally, at eight weeks, Vonoprazan exhibited 82.5% complete resolution and 17.5% sufficient relief, while Dexlansoprazole showed 87.5% and 12.5% (p=0.53).

Secondary Outcomes:

Table (3) and Figure (1) demonstrate a statistically insignificant difference in mean reflux scores among the study groups (11.44 ± 2.10 in the Vonoprazan group [Group A] versus 10.93 ± 2.25 in Dexlansoprazole group [Group B], p = 0.30) before treatment. Following eight weeks of treatment, a statistically significant reduction in mean reflux scores (FSSG) was observed, with lower scores in group B (2.5 ± 0.78) compared to group A (3.33 ± 0.91, p < 0.001). This represents a 70.77% reduction in group A and a 77.87% reduction in group B. Furthermore, no statistically significant difference in dysmotility scores was observed between the study groups before or after eight weeks of treatment. Group A (Vonoprazan) exhibited a mean score of 6.71 ± 2.48 pretreatment and 2.26 ± 0.75 post-treatment, while group B (Dexlansoprazole) showed mean scores of 7.24 ± 1.86 and 2.20 ± 0.5, respectively (p=0.27 pretreatment, p=0.68 post-treatment). The percentage reduction in dysmotility scores was 63.56% in group A and 62.79% in group B.

Tables (4) and Figure (2) reveal no statistically significant difference in LA classification between groups A and B at baseline or following eight weeks of treatment (p=0.56, 0.71, respectively). However, statistically significant differences were observed in LA classifications within both groups when comparing baseline and post-treatment (eight-week) assessments. In group A (Vonoprazan), this involved changes from 30.0% to 52.5% in grade A, 37.5% to 27.5% in grade B, 22.5% to 12.5% in grade C, and 10.0% to 7.5% in grade D (p=0.002*). Similarly, in group B (Dexlansoprazole), changes were observed from 32.5% to 50.0% in grade A, 37.5% to 30.0% in grade B, 27.5% to 17.5% in grade C, and 2.5% to 2.5% in grade D (p=0.004).