Long-term maintenance treatment of reflux esophagitis with omeprazole

Thirty-four patients with H₂-blocker-resistant reflux esophagitis subsequently healed by 40 mg omeprazole daily entered a maintenance study with 20 mg omeprazole. In 31 evaluable cases the observation period was at least 12 months (mean 24 months). Esophagitis remained in remission in two thirds of patients despite dose reduction. Relapses of esophagitis occurred in 10 cases within six months, which rapidly healed by increasing the omeprazole dose to 40 mg. No further recurrences with 20 mg omeprazole was found later than six months. Peptic strictures primarily requiring repeated dilatation in six patients during healing with omeprazole did not reappear while on omeprazole maintenance. Major side effects that could be attributed to omeprazole were not observed. Gastrin levels remained within or slightly above the normal range in the vast majority. It is concluded that omeprazole maintenance treatment in severe reflux esophagitis is an effective and safe therapy.Preliminary results have been presented at the Annual Meeting of the American Gastroenterological Association, San Antonio, 1990, and appeared as an abstract (22).This study was supported by the Deutsche Forschungsgemeinschaft, grant Ko 847/1-4. The skillful technical assistance of Mrs. E. Bothe-Sandfort and Mrs. J. Dionysius is gratefully acknowledged.     

Omeprazole in H2 receptor antagonist-resistant reflux esophagitis

We conducted a retrospective review of 25 patients with severe reflux esophagitis treated with omeprazole because of failure of H2 receptor antagonists to heal their esophagitis. Prior to beginning omeprazole (40 mg/day), all patients were on H2 antagonists for at least 9 months and still had endoscopic evidence of longitudinal (grade II) or circumferential (grade III) distal esophageal ulceration. Omeprazole therapy brought about complete endoscopic healing in 24 of 25 patients (96%). Twenty-three of 24 healed patients were then restarted on H2 antagonists as maintenance therapy. Repeat endoscopy was performed if symptoms recurred. Fourteen of 24 patients (58%) had recurrence of endoscopic esophagitis documented between 26 and 300 days from the time of starting maintenance therapy. Two of these 14 patients opted for antireflux surgery, whereas the remaining 12 were once again given omeprazole, which again resulted in symptom resolution in all patients. These data suggest that most patients with H2 receptor antagonist-resistant ulcerative esophagitis cannot be successfully maintained on H2 antagonists even after the ulcers have been healed with omeprazole. Further studies are required to determine the role of omeprazole compared to other treatments in the long-term maintenance therapy of these patients.     

Maintenance therapy for erosive esophagitis in children after healing by omeprazole: is it advisable?

OBJECTIVES: To evaluate the efficacy of acid-suppressive maintenance therapy for gastroesophageal reflux disease (GERD) in children, after the healing of reflux esophagitis. METHODS: Forty-eight children (median age 105 months, range 32-170) with erosive reflux esophagitis were initially treated with omeprazole 1.4 mg/kg/day for 3 months. Patients in endoscopic remission were assigned in a randomized, blinded manner by means of a computer-generated list to three groups of 6-month maintenance treatment: group A (omeprazole at half the starting dose, once daily before breakfast), group B (ranitidine 10 mg/kg/day, divided in two doses), and group C (no treatment). Endoscopic, histological, and symptomatic scores were evaluated at: T0, enrollment; T1, assessment for remission at 3 months after enrollment (healing phase); T2, assessment for effective maintenance at 12 months after T0 (3 months after the completion of the maintenance phase). Relapse was defined as the recurrence of macroscopic esophageal lesions. After the completion of the maintenance phase, patients without macroscopic esophagitis relapse were followed up for GERD symptoms for a further period of 30 months. RESULTS: Of 48 initially treated patients, 46 (94%) healed and entered the maintenance study. For all patients, in comparison to T0, the histological, endoscopic, and symptomatic scores were significantly reduced both at T1 and T2 (P<0.0001, for each). No significant difference was found in these three scores, comparing group A, B, and C at T1 and T2. A relapse occurred in one patient only, who presented with macroscopic esophageal lesions at T2. Three months after the completion of the maintenance phase, 12 (26%) patients complained of symptoms sufficiently mild to discontinue GERD therapy, excluding the patient who showed macroscopic esophagitis relapse. Three of 44 (6.8%) patients reported very mild GERD symptoms within a period of 30 months after maintenance discontinuation. CONCLUSIONS: Our pediatric population showed a low rate of erosive esophagitis relapse and GERD symptom recurrence long term after healing with omeprazole, irrespective of the maintenance therapy.     

Daily low-dose versus alternate day full-dose lansoprazole in the maintenance treatment of reflux esophagitis

OBJECTIVE: For the long term maintenance treatment of reflux esophagitis several strategies have been proposed with the aim of reducing the daily dosage or the frequency of drug administration. However, the available clinical studies are scarce and are often not controlled or conducted on a reduced number of cases. We aimed to compare the efficacy of two doses of lansoprazole (15 mg once daily and 30 mg on alternate days) in maintaining endoscopic healing and symptom relief over a 6-month period. METHODS: One hundred thirty-seven patients with Savary-Miller grades I-III reflux esophagitis healed after an 8-wk treatment with lansoprazole (30 mg daily) were divided into two main groups for a 6-month maintenance therapy period: lansoprazole, 15 mg once daily (group 15qd) and lansoprazole, 30 mg on alternate days (group 30qod). These two main groups were further subdivided according to the time of drug administration; morning (15qdm and 30qodm) and evening (15qde and 30qode). Each patient underwent esophagogastroduodenoscopy before entry into the study, after 8 wk of acute therapy, and after 6 months of maintenance therapy; 24-h esophageal-gastric pH monitoring was performed at baseline and during the last week of maintenance therapy. RESULTS: At the end of the maintenance period the recurrence of esophagitis was observed in 12.1% of group 15qd patients and in 19.0% of group 30qod patients, without significant differences between the two groups. The frequency of patients without reflux symptoms after the 6-month period was the same for both groups; however, a significant increase of heartburn was observed in group 30qod patients (from 12.1% to 28.6%, p = 0.007). The time of drug administration (morning and evening) had no influence on the outcome of treatment. Both regimens significantly reduced esophageal acid exposure time and increased the median 24-h gastric pH. CONCLUSIONS: Both long term lansoprazole regimens are equally effective in preventing the recurrence of esophagitis, independent of the modality of drug administration. The daily administration seems to have a better effect on the prevention of symptom recurrence.     

Omeprazole maintenance therapy prevents recurrent ulcer bleeding after surgery for duodenal ulcer

AIM: To evaluate the omeprazole maintenance therapy in patients with recurrent ulcer bleeding after surgery for duodenal ulcer. METHODS: We studied 15 consecutive patients with recurrent ulcer bleeding after surgery for duodenal ulcer. Omeprazole (20 mg/d) maintenance therapy was given after ulcer healing. In addition to clinical follow-up, ambulatory 24-h gastric pH assay was performed before and during omeprazole therapy in those patients and controls with previous duodenal ulcer surgery but no ulcer recurrence. RESULTS: All the 15 ulcers were healed after being treated with omeprazole (40 mg/d) for 2 mo. Eleven patients with two (1-9) episodes of recurrent ulcer bleeding completed the follow-up (43, 12-72 mo). None of them had a bleeding episode while on omeprazole. One patient discontinued the therapy and had recurrent bleeding. The median 24-h fraction time of gastric pH<4 in patients was 80, 46-95%, and was reduced to 32, 13-70% by omeprazole (P=0.002). CONCLUSION: Long-term maintenance therapy with omeprazole (20 mg/day) is effective in preventing recurrent ulcer bleeding.     

Determinants of Long-Term Outcome of Patients with Reflux-Related Ear, Nose, and Throat Symptoms

Gastroesophageal reflux disease (GERD) is present in up to 75% of patients with chronic refractory ear, nose, and throat (ENT) symptoms, and proton pump inhibitor (PPI) therapy induces symptom relief in the majority of these patients. It has been suggested that endoscopic findings and quantification of esophageal acid exposure may help to predict the long-term outcome of medical therapy, but prospective studies that confirm this hypothesis are lacking. The aim of the present study was to investigate the relationship of endoscopic findings and quantification of reflux with long-term outcome in patients with reflux-related ENT symptoms. One hundred six consecutive patients with chronic refractory unexplained ENT symptoms underwent upper GI endoscopy, 24-hr dual-channel esophageal pH and Bilitec (n = 35) monitoring, and esophageal manometry. Subsequently, all were treated with omeprazole, 20 mg b.i.d., and patients were followed at 2-week intervals until symptom relief. Four weeks later, omeprazole therapy was gradually decreased and the lowest effective omeprazole maintenance dose, if any, was determined. Eighty-one patients (49 men; mean age, 50) experienced a clear or excellent therapeutic response after, on average, 4 weeks of omeprazole, 20 mg b.i.d. In 36 patients (44%; group A), PPI treatment could be stopped completely, 27 patients (33%; group B) required a maintenance dose of omeprazole, 20 mg/day, and 18 patients (22%; group C) required maintenance with omeprazole, 40 mg/day. The prevalence of reflux esophagitis was significantly lower in group A patients, who also had significantly lower distal esophageal acid exposure, proximal esophageal acid exposure, and esophageal duodenogastroesophageal reflux exposure compared to groups B and C. Multivariate analysis identified the presence of esophagitis and pathological distal esophageal acid exposure as risk factors for the need of maintenance therapy. In patients with reflux-related ENT symptoms, initial findings on upper GI endoscopy and 24-hr pH-metry help to predict the need for maintenance therapy.     

Comparison of omeprazole and ranitidine in treatment of refractory gastroesophageal reflux disease in patients with gastric acid hypersecretion

Secretion of gastric acid and volume, serum gastrin concentration, and ambulatory 24-hr esophageal pH monitoring were evaluated prospectively in 12 patients with idiopathic gastric acid hypersecretion (basal acid output greater than 10.0 meq/hr) undergoing treatment for refractory chronic long-standing pyrosis. Treatment lasted six months and consisted of three months of ranitidine (mean 2150 mg/day, range 1200–3000 mg/day), followed by three months of omeprazole (mean 33 mg/day, range 20–60 mg/day). Both ranitidine and omeprazole significantly reduced gastric acid output (P<0.001) and gastric volume output (P<0.001) compared to a basal evaluation and resulted in complete disappearance of pyrosis. Total reflux time (percent 24 hr intraesophageal pH less than 4) was significantly reduced by ranitidine (P<0.02) and omeprazole (P<0.001) compared to basal evaluation; however, the effects of omeprazole were significantly greater than ranitidine (P<0.05). Omeprazole caused a significant increase in serum gastrin concentration compared to both basal and ranitidine (P<0.05). Endoscopically documented erosive esophagitis was present in nine of the 12 patients, and seven of the 12 patients had Barrett's epithelium. All 12 patients had complete resolution of pyrosis and healed esophagitis by six months, but no significant endoscopic regression was observed in the extent of Barrett's epithelium. No side effects occurred with these high doses of ranitidine or omeprazole. These results indicate that high-dose ranitidine and omeprazole are effective therapy for refractory gastroesophageal reflux disease. However, with omeprazole, total reflux times are reduced more than with ranitidine, often into the normal range. That marked reduction of gastric acid secretion with omeprazole, which greatly reduces total reflux times, accounts for the significant elevation of serum gastrin concentration seen during omeprazole therapy.     

Maintenance of healed erosive esophagitis: a randomized six-month comparison of esomeprazole twenty milligrams with lansoprazole fifteen milligrams.

BACKGROUND AND AIMS: The aim was to compare esomeprazole with lansoprazole for the maintenance of healed erosive esophagitis and resolution of gastroesophageal reflux disease-related symptoms in a United States population. METHODS: Patients who entered this double-blind, randomized, parallel-group, multicenter, maintenance trial had been treated and healed (no endoscopic evidence of erosive esophagitis) with esomeprazole 40 mg or lansoprazole 30 mg once daily (patients with Los Angeles grades C and D erosive esophagitis at baseline) or esomeprazole 40 mg (patients with Los Angeles grades A and B erosive esophagitis at baseline) and had no heartburn or acid regurgitation symptoms during the previous week. Patients were randomized to maintenance once-daily therapy with esomeprazole 20 mg (n = 512) or lansoprazole 15 mg (n = 514) for up to 6 months. Esophago-gastroduodenoscopies were done at months 3 and 6, and investigators assessed symptom severity at months 1, 3, and 6. Endoscopic/symptomatic remission was defined as no erosive esophagitis and no study withdrawal as a result of reflux symptoms. RESULTS: The estimated endoscopic/symptomatic remission rate during a period of 6 months was significantly higher (P = .0007) for patients who received esomeprazole 20 mg once daily (84.8%) compared with those who received lansoprazole 15 mg (75.9%). Most patients had no heartburn (383/462 and 369/466) or acid regurgitation (401/462 and 400/466) symptoms at 6 months, and there were no significant differences between treatments. Both treatments were well-tolerated. CONCLUSION: Esomeprazole 20 mg is more effective than lansoprazole 15 mg in maintaining endoscopic/symptomatic remission in patients with healed erosive esophagitis.     

Pattern of acid reflux in patients with reflux esophagitis 'resistant' to H2-receptor antagonists

Ambulatory 24-h esophageal pH monitoring was carried out in 54 patients with erosive/ulcerative reflux esophagitis before a 12- to 24-week treatment with either ranitidine, 150 to 300 mg twice daily, or famotidine, 20 to 40 mg twice daily. After this period, 21 patients continued to present endoscopic evidence of esophagitis. Patients who did not respond to the therapy showed a more severe pretreatment pattern of acid reflux than those who healed, with regard to both median percentage time of reflux (16.2% versus 11.0%, respectively, p less than 0.05) and median number of reflux episodes (88.0 versus 55.0; p less than 0.05). Ambulatory 24-h esophageal pH-metry is therefore to be recommended in all patients with acid reflux symptoms, even in those who already show endoscopic lesions of the esophageal mucosa, since this test is a valid prognostic indicator of response to treatment.     

Omeprazole versus high-dose ranitidine in mild gastroesophageal reflux disease: short- and long-term treatment. The Dutch Reflux Study Group

OBJECTIVE: Patients with reflux esophagitis suffer from a chronic condition that may cause considerable discomfort because of recurrent symptoms and diminished quality of life. This study was designed to evaluate acute and long-term treatment comparing standard doses of omeprazole and high-dose ranitidine. METHODS: Patients with endoscopically verified symptomatic esophagitis grade I or II were initially treated with omeprazole 20 mg daily or ranitidine 300 mg twice daily for 4-8 wk. Patients who were symptom free were randomized to maintenance treatment with omeprazole 10 mg daily or ranitidine 150 mg twice daily. Patients were seen every 3 months or at symptomatic relapse. RESULTS: The percentage of asymptomatic patients after 4 and 8 wk treatment were 61% and 74%, respectively, for omeprazole and 31% and 50%, respectively, for ranitidine. Of 446 patients treated initially, 277 were asymptomatic, of whom 263 entered the maintenance study. The estimated proportion of patients in remission after 12 months of maintenance treatment with omeprazole 10 mg daily (n = 134) and ranitidine 150 mg twice daily (n = 129) were 68% and 39%, respectively (p < 0.0001). CONCLUSIONS: Omeprazole 20 mg daily is superior to high-dose ranitidine in the symptomatic treatment of reflux esophagitis grade I and II. Furthermore, omeprazole at half the standard dose is more effective than ranitidine in a standard dose in keeping patients in remission for a period of 12 months.     

Efficacy of pantoprazole 20 mg daily compared with esomeprazole 20 mg daily in the maintenance of healed gastroesophageal reflux disease: a randomized, double-blind comparative trial - the EMANCIPATE study

OBJECTIVES: To compare the efficacy and tolerability of pantoprazole 20 mg once daily with that of esomeprazole 20 mg once daily for 6 months as maintenance therapy in patients with previously healed gastroesophageal reflux disease. METHODS: In an initial open-label acute phase, outpatients with endoscopically confirmed gastroesophageal reflux disease (Los Angeles grades A-D) received pantoprazole 40 mg once daily for 4 or 8 weeks. Those healed (defined as the absence of esophagitis, and 'no' or 'mild' heartburn and acid regurgitation) were randomized in the double-blind manner for maintenance therapy with pantoprazole 20 mg once daily or esomeprazole 20 mg once daily for 6 months. RESULTS: In the acute healing phase, 1452 patients were recruited to receive pantoprazole 40 mg once daily. Healing success was 91% (intent-to-treat analysis). A total of 1303 patients entered the maintenance phase of the study. Pantoprazole 20 mg once daily and esomeprazole 20 mg once daily were equally effective at maintaining patients in remission; 84 and 85% of pantoprazole and esomeprazole recipients remained in combined endoscopic and symptomatic remission at 6 months (intent-to-treat analysis). The confidence interval of the difference was (-5.7; +infinity), showing that pantoprazole is as effective as esomeprazole with a noninferiority margin of 5.8%. Combined endoscopic and symptomatic remission was independent of Helicobacter pylori status. Both treatments were well tolerated and safe. CONCLUSION: Treatment with pantoprazole 20 mg once daily or esomeprazole 20 mg once daily provides similarly effective and well-tolerated maintenance of previously healed gastroesophageal reflux disease irrespective of baseline H. pylori status.     

Effect of omeprazole and high doses of ranitidine on gastric acidity and gastroesophageal reflux in patients with moderate-severe esophagitis

Thirty to fifty percent of patients with reflux esophagitis fail to heal after treatment with conventional doses of H2-receptor antagonists, whereas omeprazole administration induces more than 90% healing. To investigate the effect of omeprazole and higher-than-presently-recommended doses of H2-blockers, we evaluated gastric acidity and gastroesophageal reflux in 17 patients with severe-moderate esophagitis before and after treatment with 300 mg ranitidine twice daily or 20 mg omeprazole once daily. Three pH-metric studies were performed, in a cross-over design, before and after 8 days of treatment with omeprazole or ranitidine. Both drugs significantly reduced intragastric acidity (p less than 0.001) during both night and day hours. Median hourly 24-h intragastric pH was 1.8 in the basal study, 2.9 after ranitidine, and 3.4 after omeprazole. Intragastric acidity fell from 84.0 mmol/L in the basal study to 14.2 mmol/L (79% inhibition) with ranitidine and 9.3 mmol/L (84% inhibition) with omeprazole. Patients with esophagitis were significantly more exposed to acid than healthy subjects, in both the supine and upright position (p less than 0.01). The time with esophageal pH less than 4 dropped from 23.9% in the basal study to 8.5% with ranitidine and to 7.2% with omeprazole (p less than 0.001). Both drugs significantly reduced esophageal exposure to acid in both the supine and upright positions (p less than 0.001), whereas neither had any effect on esophageal acid clearance.     

High-Dose Famotidine in the Maintenance Treatment of Refractory Esophagitis: Results of a "Medium-Term" Open Study

Forty-four patients with esophagitis refractory to standard H2-blocker therapy, who had healed after a 4- to 16-wk course with either 20-40 mg omeprazole or ranitidine at doses of 300-600 mg daily in a randomized double-blind study, commenced a 3-month maintenance course of therapy with 40 mg bid famotidine. The aims of this investigation were to assess the effectiveness of this regimen in preventing recurrence of esophagitis lesions and symptoms in this subgroup of patients with therapy-resistant disease and to verify whether patients previously healed with omeprazole have a higher recurrence rate than those healed with ranitidine. The results of the study show that, despite the high dose of famotidine, 48% of patients relapsed within 3 months, a third of whom were asymptomatic. Moreover, previous omeprazole treatment is associated with a significantly higher risk of recurrence.     

Esomeprazole once daily for 6 months is effective therapy for maintaining healed erosive esophagitis and for controlling gastroesophageal reflux disease symptoms: a randomized, double-blind, placebo-controlled study of efficacy and safety

OBJECTIVE: Esomeprazole, the S-isomer of omeprazole, achieves a significantly greater healing rate and symptom resolution of erosive esophagitis than that achieved by omeprazole. The objective of this study is to assess the efficacy of the new proton pump inhibitor esomeprazole in preventing relapse over a prolonged period in patients with healed erosive esophagitis. METHODS: A total of 318 gastroesophageal reflux patients whose erosive esophagitis was healed in a comparative study of esomeprazole 40 mg, 20 mg, or omeprazole 20 mg, were randomized to maintenance therapy with once daily esomeprazole 40 mg, 20 mg, or 10 mg, or placebo in a U.S., double-blind multicenter trial. RESULTS: After 6 months, healing was maintained (cumulative life table rates) in 93.6% (95% CI 87.4-99.7) of patients treated with esomeprazole 40 mg, 93.2% (95% CI 87.4-99.0) treated with esomeprazole 20 mg, and 57.1% (95% CI 45.2-69) treated with esomeprazole 10 mg; p < 0.001 vs placebo (29.1%; 95% CI 17.7-40.3). Of patients relapsing, mean time to first recurrence of esophagitis increased with dose, from 34 days (placebo) to 78 days (10 mg), 115 days (20 mg), and 163 days (40 mg). Patients treated with esomeprazole had less frequent and less severe heartburn than those treated with placebo. At month 6, more than 70% of patients being treated with esomeprazole remained symptom-free. CONCLUSIONS: Esomeprazole is effective and well tolerated in the maintenance of a healing erosive esophagitis. Esomeprazole 40 mg and 20 mg maintain healing in over 90% of patients while providing effective control of heartburn symptoms.     

Stability of gastric secretory inhibition during 6-month treatment with omeprazole in patients with gastroesophageal reflux disease

OBJECTIVE: A trend toward relapse of reflux symptoms and esophagitis during long-term treatment with proton pump inhibitors has been reported. The purpose of this study was to evaluate the existence of tachyphylaxia to the effect of proton pump inhibitors on gastric acidity and gastroesophageal reflux over time. METHODS: A total of 23 patients with reflux esophagitis underwent 24-h intragastric and intraesophageal pH-metry after 7, 90, and 180 days of continued dosing with 20 mg of omeprazole once daily before breakfast. RESULTS: The total median percentages of time gastric pH <4 (interquartile range) were 49% (35-70%), 60% (36-76%), and 42% (26-66%) after 7, 90, and 180 days (p = 0.14). Percentages of time gastric pH <3 were 41%, 54%, and 34%, respectively (p = 0.19). The median percentages of total time esophageal pH <4 were 1.1%, 2.5%, and 1.1%, respectively (p = 0.70). Healing of esophagitis was achieved in 84% of the patients after 6 months. Heartburn improved in six, worsened in three, and was unchanged in 10 patients (p = 0.16). There was no statistical significant relationship between change in esophageal acid exposure and change in severity of heartburn. CONCLUSIONS: A dose of 20 mg of omeprazole once daily consistently controlled patients' symptoms and kept gastric acidity at a stable level over a period of 6 months. There is no evidence of diminution in the effects of 20 mg of omeprazole over time that could indicate the development of tolerance.     

Pattern of Acid Reflux in Patients with Reflux Esophagitis ‘Resistant’ to H2-Receptor Antagonists

Ambulatory 24-h esophageal pH monitoring was carried out in 54 patients with erosive/ulcerative reflux esophagitis before a 12- to 24-week treatment with either ranitidine, 150 to 300 mg twice daily, or famotidine, 20 to 40 mg twice daily. After this period, 21 patients continued to present endoscopic evidence of esophagitis. Patients who did not respond to the therapy showed a more severe pretreatment pattern of acid reflux than those who healed, with regard to both median percentage time of reflux (16.2% versus 11.0%, respectively, p < 0.05) and median number of reflux episodes (88.0 versus 55.0; p < 0.05). Ambulatory 24-h esophageal pH-metry is therefore to be recommended in all patients with acid reflux symptoms, even in those who already show endoscopic lesions of the esophageal mucosa, since this test is a valid prognostic indicator of response to treatment.     

Comparative study of nizatidine and famotidine for maintenance therapy of erosive esophagitis

BACKGROUND: The therapeutic effect of combined administration of prokinetics and histamine H2 receptor antagonists (H2RA) in gastroesophageal reflux disease is reported to be superior to that of monotherapy with H2RA alone. In addition to its acid-suppressing effect, the H2RA nizatidine also has a prokinetic action by suppressing acetylcholine esterase. The present multicenter, randomized controlled study was performed to investigate whether nizatidine is superior to famotidine, which does not suppress acetylcholine esterase activity, in maintenance therapy for erosive esophagitis. In addition, the question as to whether the grade of erosive esophagitis affects the non-recurrence rate during the maintenance therapy with H2RA was also investigated. METHODS: Seventy-two patients with endoscopically healed erosive esophagitis after 8 weeks of initial treatment with proton pump inhibitors were randomly divided into two groups. Patients in the nizatidine group were treated with 150 mg nizatidine twice a day (b.i.d.), while patients in the famotidine group were treated with 20 mg famotidine b.i.d. for 6 months. At the end of therapy, and at the time when patients complained of symptoms, endoscopic investigations were repeated to find out whether the esophagitis had recurred. RESULTS: Nizatidine produced a significantly higher non-recurrence rate than famotidine (P = 0.049 in intention-to-treat [ITT] analysis). This difference of remission rate between nizatidine and famotidine was observed mainly in grade B esophagitis (P = 0.016 in ITT analysis). CONCLUSION: Nizatidine is a more effective H2RA than famotidine in the maintenance therapy of patients with reflux esophagitis.     

Omeprazole 10 mg or 20 mg once daily in the prevention of recurrence of reflux oesophagitis. Solo Investigator Group.

This study determined the optimal maintenance dose of omeprazole in reflux oesophagitis. One hundred and ninety three patients rendered asymptomatic and healed after four or eight weeks omeprazole were randomised double blind to 10 mg omeprazole once daily (n = 60 evaluable), 20 mg omeprazole once daily (n = 68), or placebo (n = 62) for one year or until symptomatic relapse. Each omeprazole regimen was superior to placebo in preventing both symptomatic relapse (life table analysis, p < 0.001) and endoscopically verified relapse (p < 0.001). At 12 months, the life table endoscopic remission rates (proportions of patients without grade > or = 2 oesophagitis) were: 50% (95% confidence intervals 34 to 66%) with 10 mg omeprazole once daily, 74% (62 to 86%) with 20 mg omeprazole once daily, and 14% (2 to 26%) with placebo. At 12 months, the life table symptomatic remission rates (proportions of patients asymptomatic or with mild symptoms) were: 77% (64 to 89%) with 10 mg omeprazole once daily, 83% (73 to 93%) with 20 mg omeprazole once daily, and 34% (16 to 52%) with placebo. Both 10 mg and 20 mg omeprazole once daily were effective in prolonging the remission of reflux oesophagitis: 10 mg may be appropriate to start longterm treatment, though the existence of a dose response relation means that 20 mg once daily may be effective in patients for whom 10 mg once daily is suboptimal.     

Failure of Initial 24-Hour Esophageal pH Monitoring to Predict Refractoriness and Intractability in Reflux Esophagitis

Prolonged esophageal pH monitoring is considered to be the most sensitive and specific test for the diagnosis of gastroesophageal reflux disease (GERD). However, the role of pH monitoring in predicting the clinical and endoscopic response of reflux esophagitis is not well defined. In this study, 106 patients with moderate to severe symptoms of GERD and esophagitis (grades 0-IV) by endoscopy were initially studied by ambulatory esophageal pH monitoring, and their clinical response to standard H2 antagonist therapy was monitored at 8 wk. Refractory patients were defined as those who failed to heal and/or had intractable reflux symptoms after 8 wk of H2 antagonist therapy, and who required continuous therapy with higher doses of H2 antagonists, addition of prokinetic agents, or omeprazole. There was a positive correlation (r = 0.89) between endoscopic severity of esophagitis upon entry into the study and refractoriness to standard medical therapy. However, there were no differences in the various pH parameters analyzed between the 58 patients who responded and the 48 patients who were refractory to medical therapy, regardless of the endoscopic grading of their esophagitis. We conclude that 24-h ambulatory esophageal pH monitoring does not predict refractoriness of reflux esophagitis to standard therapy. The decision for more aggressive methods of treatment probably requires assessment of symptomatic and endoscopic response after 8 week standard H2 antagonist therapy.     

The effect of omeprazole or ranitidine treatment on 24-hour esophageal acidity in patients with reflux esophagitis

Twenty-two consecutive patients with gastroesophageal reflux and erosive or ulcerative esophagitis entered a double-blind, randomized study comparing the effect of 20 mg omeprazole once daily with that of 150 mg ranitidine twice daily on esophageal acidity. Ambulatory 24-h esophageal pH measurements were performed within 1 month before inclusion and after 3 weeks of medication. Omeprazole significantly (p less than 0.05) reduced the number of reflux (pH less than 4) episodes, the number of refluxes lasting greater than 5 min, and the total reflux time. In contrast, ranitidine significantly reduced only the total reflux time. When the two treatment groups were compared, a significant difference in favor of omeprazole was found for daytime and total reflux values, except for the longest reflux and the number of reflux episodes lasting greater than 5 min. Substantial differences, also in favor of omeprazole, were found with regard to the effect on endoscopic healing of the esophagitis.