Background <p>The aim of this study is to optimize Helicobacter pylori (H. pylori) eradication by increasing the proton pump inhibitor (PPI) dose and reducing the treatment duration of antibiotics without compromising the treatment’s safety and efficacy.</p> Methods <p>This pilot randomized controlled trial included 120 patients from Notre Dame des Secours University Hospital in Byblos, Lebanon, between February 2023 and December 2023. Participants were Lebanese adults with H. pylori infection confirmed by upper gastrointestinal endoscopy. Exclusion criteria included pregnancy or nursing, malignancy or gastric mucosa-associated lymphoid tissue lymphoma, allergy or contraindications to study drugs, active upper gastrointestinal bleeding, prior gastric surgeries, recent use of PPIs or antibiotics, celiac disease, previous H. pylori treatment, or refusal to consent. Eligible patients (<i>n</i> = 113) were randomly assigned into three groups: Group A (<i>n</i> = 38) received a standard-dose of rabeprazole 20 mg twice daily for 14 days with concomitant therapy, Group B (<i>n</i> = 37) received a double-dose of rabeprazole (20 mg twice per day) for 10 days with concomitant therapy, and Group C (<i>n</i> = 38) received a high-dose of rabeprazole (20 mg three times per day) for 10 days with concomitant therapy. Eradication was assessed by urea breath test six weeks after treatment completion.</p> Results <p>Out of 120 participants, 101 patients were considered for analysis, while 19 patients were excluded (15.8%). Of these exclusions, 7 patients were excluded before randomization due to drug allergy and opted for alternative treatment (5.8%), while 12 were excluded after randomization due to loss to follow-up (12%). The results indicated that the high-dose PPI group C had the highest percentage of negative breath tests (100%), followed by the standard treatment group A with 94.7%, and then group B with 83.3%. However, given the pilot nature and sample size of this study, these results, particularly the 100% rate in Group C, should be interpreted as preliminary and require confirmation in a larger trial.</p> Conclusion <p>The use of high-dose PPI with 10 days of concomitant therapy (Group C) demonstrated the highest eradication rate among the study groups. This promising finding suggests a potential benefit of the high-dose PPI regimen with 10-day concomitant therapy but must be interpreted with caution; it warrants further investigation in a larger and adequately powered randomized controlled trial to confirm its efficacy and generalizability, given the pilot nature of this study.</p> Name of the registry <p>Lebanon clinical trial registry;</p> Trail registration number <p>LBCTR2025075755;</p> Date of registration in primary registry <p>14/08/2025.</p>