Omeprazole versus ranitidine or ranitidine/metoclopramide in poorly responsive symptomatic gastroesophageal reflux disease

Objectives: To evaluate complete symptom resolution, mucosal healing, and tolerability of omeprazole, ranitidine, or ranitidine/metoclopramide in patients with poorly responsive, symptomatic gastroesophageal reflux disease (GERD). Methods: Adults with persistent symptomatic GERD after ranitidine treatment were stratified by esophagitis grade and randomized to omeprazole 20 mg once daily, ranitidine HCl 150 mg twice daily, or ranitidine HCl 150 mg twice daily plus metoclopramide HCl 10 mg four times daily. Endoscopies were conducted at baseline and at wk 4 and 8. Patients assessed overall symptom improvement at wk 4 and 8 and evaluated daytime and nighttime heartburn, dysphagia, and acid regurgitation daily. Results: After 1 wk, 13% of patients receiving omeprazole (N = 100) had complete resolution of all GERD symptoms versus 1% and 3% of patients receiving ranitidine (N = 97) or ranitidine/metoclopramide (N = 93), respectively (p < 0.001). More patients receiving omeprazole had complete symptom resolution at wk 4 (33%) and at the end of the study (64%; both p < 0.001) than patients receiving ranitidine (8% and 28%, respectively) or ranitidine/metoclopramide (7% and 29%, respectively). Regardless of baseline esophagitis grade, more patients receiving omeprazole had complete symptom resolution. At wk 8, more than 91% of patients with grade 0 or 1 esophagitis at baseline were still healed irrespective of treatment. At wk 8, 80% of patients with esophagitis grade 2 or higher at entry were healed with omeprazole (p < 0.001 vs ranitidine [40%] and ranitidine/metoclopramide [46%]). Thirty-four percent of patients reported an adverse event. Significantly more patients receiving combination treatment reported an adverse event than patients treated with single agents. Conclusions: in patients with persistent GERD symptoms after ranitidine, omeprazole (20 mg daily for up to 8 wk) provides faster and more complete resolution of common GERD symptoms than continued ranitidine (300 mg daily) alone or in combination with metoclopramide (40 mg daily). Omeprazole provides significantly higher rates of endoscopic healing than ranitidine alone or with metoclopramide. Omeprazole and ranitidine are generally well tolerated. The addition of metoclopramide to ranitidine significantly increases adverse events.