Background: Gastroesophageal reflux disease (GERD) is a prevalent chronic acid-related disorder that substantially impairs patient quality of life. Proton pump inhibitors (PPIs) are established therapy; however, first-generation agents such as omeprazole show clinically relevant inter-individual variability related in part to cytochrome P450 2C19 (CYP2C19) metabolism. Ilaprazole, a newer PPI with predominant cytochrome P450 3A4 (CYP3A4) metabolism and a longer elimination half-life, may provide more consistent acid suppression, but direct comparative data in Indian patients with GERD and erosive gastritis using validated quality-of-life tools remain limited. Aim: To compare the clinical efficacy, health-related quality-of-life outcomes, and safety of ilaprazole 10 mg once daily versus omeprazole 20 mg once daily over eight weeks in patients with symptomatic GERD and endoscopically confirmed erosive gastritis. Erosive esophagitis was not required for inclusion and was not the primary condition studied. Methodology: A prospective, single-center, single-blind, comparative clinical study was conducted at VMKVMC&H, Salem, Tamil Nadu. Sixty patients fulfilling the inclusion criteria were randomly assigned in a 1:1 ratio to either ilaprazole 10 mg (n=30) or omeprazole 20 mg (n=30) once daily before breakfast for eight weeks. Participants were blinded to treatment allocation, while treating investigators were aware of allocation for dispensing and safety monitoring. Primary outcomes were change in GERD symptom count and health-related quality of life assessed using the 25-item QOLRAD questionnaire across five domains: Emotional distress, sleep disturbance, food/drink problems, physical/social functioning, and vitality. The theoretical QOLRAD total score range is 25-175, with higher scores indicating better quality of life. Adverse drug reactions, adherence, and concomitant/rescue medication use were assessed at follow-up visits. Baseline imbalances in symptom count and choking sensation were taken into account when analysing efficacy outcomes. Results: The groups were comparable in age (35.8±6.3 vs 37.2±4.8 years; p=0.352), and sex distribution was similar but not identical (male 53.3% vs 50.0%; p=1.000). Baseline QOLRAD total scores were comparable (34.07±9.10 vs 33.13±7.73; p=0.965). Baseline symptom count was higher in the omeprazole group (7.90±0.61 vs 7.10±0.96; p<0.001), and choking sensation was present only in the omeprazole group (36.7% vs 0%); therefore, we analysed symptom-count findings with caution, focusing on change from baseline. By week 8, ilaprazole was associated with a higher QOLRAD total score than omeprazole (146.57±4.14 vs 103.63±32.26; p<0.001; Cohen's d=1.706; mean difference 42.94, 95% CI 30.81-55.07). Mean GERD symptom count declined from 7.10±0.96 to 0.67±0.48 with ilaprazole (90.6% reduction) versus 7.90±0.61 to 3.10±1.18 with omeprazole (60.8% reduction). At week 8, ilaprazole showed higher point-in-time symptom resolution for epigastric pain, nausea, irritating throat sensation, belching, and loss of appetite. The week 4-to-week 8 nausea pattern was clarified as point-in-time symptom status, because symptoms could recur or be re-reported at the final visit. Adverse drug reactions were mild and comparable between groups (10.0% vs 13.3%; p>0.05), with no serious adverse events in either arm. Conclusion: Ilaprazole 10 mg once daily was associated with greater improvement in GERD symptom burden and health-related quality of life than omeprazole 20 mg once daily over eight weeks, with a comparable safety profile. However, because this was a small, single-center, single-blind study with baseline symptom imbalance and without CYP genotyping, pharmacokinetic assessment, intragastric pH monitoring, or repeat endoscopy, we regard these findings as preliminary and requiring confirmation in larger, methodologically rigorous trials. Pharmacogenomic and pharmacological explanations should be regarded as plausible hypotheses rather than proven mechanisms.

gastroesophageal reflux disease, ilaprazole, omeprazole, proton pump inhibitor, quality of life