Omeprazole v ranitidine for prevention of relapse in reflux oesophagitis. A controlled double blind trial of their efficacy and safety.

The aim of this study was to compare recurrence rates of reflux oesophagitis (after endoscopic healing with omeprazole) over a 12 month period of randomised, double blind, maintenance treatment with either daily omeprazole (20 mg every morning; n = 53), weekend omeprazole (20 mg on three consecutive days a week, n = 55) or daily ranitidine (150 mg twice daily, n = 51). Patients were assessed for relapse by endoscopy (with gastric biopsy) at six and 12 months, or in the event of symptomatic recurrence, and serum gastrin was monitored. At 12 months, the estimated proportions of patients in remission (actuarial life table method) were 89% when receiving daily omeprazole compared with 32% when receiving weekend omeprazole (difference 57%, p < 0.001, 95% confidence intervals: 42% to 71%) and 25% when receiving daily ranitidine (difference 64%, p < 0.001, 95% confidence intervals: 50% to 78%). Median gastrin concentrations increased slightly during the healing phase, but remained within the normal range and did not change during maintenance treatment. No significant pathological findings were noted, and no adverse events were attributable to the study treatments. In conclusion, for patients who respond favourably to acute treatment with omeprazole 20 mg every morning, the drug is a safe and highly effective maintenance treatment for preventing relapse of reflux oesophagitis and its associated symptoms over 12 months. By contrast, weekend omeprazole and daily ranitidine were ineffective.     

Erosive oesophagitis: outcome of repeated long term maintenance treatment with low dose omeprazole 10 mg or placebo

Aims—To investigate the efficacy of dailymaintenance treatment with omeprazole 10 mg in reducing the relapserate of healed erosive oesophagitis.
Methods—Three hundred patients with erosiveoesophagitis (grade 2 or greater) received omeprazole 20 mg daily for12 weeks, followed by 40 mg daily for a further 12 weeks if required.After healing, patients were randomised to double blind treatment with omeprazole 10 mg daily or placebo for up to 18 months. On relapse thetreatment cycle was repeated.
Results—The cumulative healing rate at 12 weeksin the initial healing period was 95%, and 96% and 98% on rehealingcourses after relapse in the first and second maintenance periodsrespectively. After 12 weeks of treatment, 98% of patients were freefrom heartburn and 97% were free of all reflux related symptoms.Relapse in the subgroup of patients who relapsed in both maintenanceperiods was infrequent on omeprazole 20 mg daily: only 9% at twoyears. Gastrin concentrations rose above normal in one third ofpatients. One patient had linear hyperplasia of endocrine cells andanother had micronodular hyperplasia. There were no side effectsdefinitely attributable to omeprazole.
Conclusion—Maintenance treatment with omeprazole10 mg daily keeps about 60% of patients with erosive oesophagitis inprolonged remission. Patients relapsing once are likely to do so again; they can subsequently be treated effectively with omeprazole 20mg daily.

Keywords:erosive oesophagitis; long term maintenancetreatment; omeprazole

     

Rabeprazole is equivalent to omeprazole in the treatment of erosive gastro-oesophageal reflux disease: A randomised, double-blind, comparative study of rabeprazole and omeprazole 20 mg in acute treatment of reflux oesophagitis, followed by a maintenance open-label, low-dose therapy with rabeprazole

BACKGROUND: Previous studies have shown similar effects of rabeprazole and omeprazole, when used at the same dose in the treatment of reflux oesophagitis. However, such studies have been conducted as superiority studies but interpreted as equivalence ones. AIM: To properly assess the comparative efficacy of rabeprazole and omeprazole in inducing complete endoscopic healing and symptom relief in patients with reflux oesophagitis. METHODS: Patients (n=560) with Savary-Miller grade I-III reflux oesophagitis were randomised in a double-blind, double-dummy fashion to rabeprazole or omeprazole 20 mg once daily for 4-8 weeks. Then, patients endoscopically healed and symptomatically relieved were openly maintained with rabeprazole 10 mg or 2x10 mg once daily (in the event of clinical and/or endoscopic relapse) for a maximum of 48 weeks. RESULTS: After 4-8 weeks of treatment, healing (primary end-point) was observed in 228/233 (97.9%) patients in the rabeprazole group and in 231/237 (97.5%) in the omeprazole one (equivalence effect demonstrated by p<0.0001 at Blackwelder test and an upper confidence limit at 97.5% of 0.023). However, rabeprazole was faster in inducing heartburn relief than omeprazole (2.8+/-0.2 versus 4.7+/-0.5 days of therapy to reach the first day with satisfactory heartburn relief, p=0.0045 at log-rank test). In the maintenance phase, 15.2% of patients had an endoscopic and/or clinical relapse. CONCLUSION: Rabeprazole is equivalent to omeprazole in healing reflux oesophagitis, but shows a faster activity on reflux symptoms in the early treatment phase.     

Effect of cisapride on relapse of reflux oesophagitis, healed with an antisecretory drug.

Maintenance treatment with cisapride was evaluated in 298 patients in whom reflux oesophagitis had been healed with antisecretory drugs. Initially, 34% of the patients had grade-I oesophagitis, 33% had grade II, and 33% had grade III. The patients were treated with 20 mg cisapride twice daily or placebo for 6 months or until endoscopic relapse was shown if this occurred earlier. Survival analysis showed that cisapride significantly prolonged the time to endoscopic relapse in grade-I patients (P = 0.02). The intergroup difference in symptomatic relapse in all patients was also significant (P = 0.010). The effect of cisapride was less clearcut in grade II or III, and/or in patients healed with omeprazole. Factors associated with early relapse were placebo therapy, prior omeprazole therapy, duration of pre-trial symptomatic period, and initial endoscopic severity grade. Adverse experiences were limited; diarrhoea was reported by 9% of the cisapride patients.     

A double-blind,randomized comparison of omeprazole Multiple Unit Pellet System (MUPS) 20 mg,lansoprazole 30 mg and pantoprazole 40 mg in symptomatic reflux oesophagitis followed by 3 months of omeprazole MUPS maintenance treatment: a Dutch multicentre trial

BACKGROUND: Proton pump inhibitors (PPIs) have proved to be effective in treating reflux oesophagitis. Until now, no study had compared the PPIs omeprazole Multiple Unit Pellet System (MUPS), lansoprazole and pantoprazole in patients with reflux oesophagitis. AIM: To compare omeprazole MUPS 20 mg, lansoprazole 30 mg and pantoprazole 40 mg for treatment effect in symptomatic reflux oesophagitis. METHOD: Patients with grade I-IV symptomatic reflux oesophagitis were randomized to double-blind omeprazole 20 mg once morning, lansoprazole 30 mg o.m. or pantoprazole 40 mg o.m. Patient satisfaction and symptoms were evaluated after 4 and 8 weeks. Patients not satisfied after 8 weeks were treated for another 4 weeks with omeprazole 40 mg MUPS (open). Successful treatment was followed by 3 months' maintenance treatment with omeprazole MUPS 20 mg (patients satisfied after 4 or 8 weeks) or omeprazole MUPS 40 mg (patients satisfied after 12 weeks). RESULTS: On intention-to-treat (ITT) analysis (n = 461) at 4 and 8 weeks, respectively, 84% and 87% (omeprazole MUPS), 78% and 81% (lansoprazole), and 84% and 89% (pantoprazole) were free of heartburn. Equivalence was found between omeprazole MUPS and pantoprazole (heartburn relief), but not with lansoprazole. Patient satisfaction after 4 and 8 weeks, respectively, was 79% and 89% (omeprazole MUPS), 76% and 86% (lansoprazole), and 79% and 91% (pantoprazole). Patient satisfaction was similar in all treatment groups. During maintenance, 87% in the omeprazole MUPS 20 mg group and 81% in the omeprazole MUPS 40 mg group were satisfied after 3 months. CONCLUSIONS: Omeprazole MUPS 20 mg and pantoprazole 40 mg have equivalent efficacy in the treatment of reflux oesophagitis. Based on patient satisfaction, omeprazole MUPS 20 mg, lansoprazole 30 mg and pantoprazole 40 mg are equally effective.     

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.     

Healing and prevention of relapse of reflux oesophagitis by cisapride.

Altogether, 138 patients were included in a study aimed at evaluating the effect of cisapride on healing and relapse of oesophagitis shown endoscopically. In the first phase of the study cisapride was given in an open fashion at 10 mg four times a day for 8 to 16 weeks, and healing was obtained in 69% of patients. Healing occurred later in patients with grades II to IV oesophagitis. The total score for reflux symptoms decreased by 67%. Eighty of the healed patients were included in the second phase. They were randomly assigned to double blind treatment with either cisapride 10 mg (n = 37) or placebo (n = 43) twice a day. Control endoscopy was performed when symptoms recurred or at the end of the six month trial. The cumulative percentage of patients in remission was higher (p = 0.06, survival analysis) in the cisapride group than in the placebo group, the relapse rates being 20% and 39%. The duration of remission tended to be longer in patients with a lower initial degree of oesophagitis. Adverse effects were no more frequent with cisapride than with placebo. In conclusion, cisapride is efficacious in healing oesophagitis, and, unlike other gastrointestinal prokinetic drugs or low dose cimetidine (400-800 mg daily) or ranitidine (150 mg daily), it may prevent relapse of oesophagitis.     

Pantoprazole 20 mg is an effective maintenance therapy for patients with gastro-oesophageal reflux disease

OBJECTIVES: To compare the efficacy of 20 mg with 40 mg pantoprazole in maintaining symptomatic and endoscopic remission in patients with gastro-oesophageal reflux disease (GORD). STUDY DESIGN: Patients (18-84 years old; n = 433) with healed GORD II or III were included in this prospective multi-centre, randomized, parallel, double-blind study. Pantoprazole was administered once daily for up to 1 year as either a 20 mg or 40 mg enteric-coated tablet to 221 and 212 patients, respectively. Symptoms of GORD were assessed every 3 months. Endoscopy was performed at entry, after 6 and 12 months, or when symptoms of GORD were perceived on at least three consecutive days. The primary efficacy parameter was the time until endoscopically proven relapse of GORD occurred (stage I or greater); the secondary parameters included tolerability, safety, and time until symptomatic relapse occurred. RESULTS: In the 20 mg treatment group, 87% and 75% of patients were in endoscopic remission after 6 and 12 months, respectively; the corresponding rates in the 40 mg treatment group were 91% and 78%. In both treatment groups, GORD stage I accounted for about 50% of endoscopic relapses. The symptomatic remission rates in the 20 mg group were estimated as 85% and 77% after 6 and 12 months, respectively; the corresponding values in the 40 mg group were 87% and 76%. No correlation was seen either between the endoscopically proven relapse and perception of symptoms, or between the severity of the pre-treatment stage of GORD and the maintenance dose of pantoprazole. Both doses were well tolerated. CONCLUSIONS: Both the 20 mg and 40 mg doses of pantoprazole are safe and effective in maintaining patients with healed reflux oesophagitis in remission. Moreover, for the majority of patients, the 20 mg dose provides adequate long-term therapeutic efficacy at a minimal drug exposure and lower costs.     

Omeprazole 20 mg three days a week and 10 mg daily in prevention of duodenal ulcer relapse. Double-blind comparative trial

In a double-blind, parallel-group clinical trial of 195 patients with duodenal ulcers who after a short-term study had relief of pain and healed ulcers proved endoscopically, 65 were randomized to receive 20 mg omeprazole 3 days a week (once in the morning from Friday to Sunday), 64 to receive 10 mg omeprazole once daily in the morning, and 66 to receive placebo for up to 6 months. The patients underwent repeat endoscopy with biopsy of the gastric fundic mucosa (qualitative assessment of argyrophilic cell population), assessment of symptoms, and laboratory screening with measurement of basal serum gastrin concentrations at 3 and 6 months or more often if indicated by recurrence of symptoms. At 3 months, endoscopically proved ulcer relapse occurred in 16% receiving 20 mg omeprazole 3 days a week; 21% receiving 10 mg omeprazole daily; and 50% receiving placebo. At 6 months, corresponding rates were 23%, 27%, and 67% with 95% confidence intervals of difference between the placebo group and omeprazole groups of 28%-60% and 24%-56% (P less than 0.00001), respectively, and between omeprazole groups of -19%-11% (NS). No major clinical or laboratory side effects were noted. Thus both omeprazole regimens are effective and safe in preventing duodenal ulcer relapse.     

Efficacy of omeprazole for the treatment of symptomatic acid reflux disease without esophagitis

BACKGROUND: Up to three quarters of patients with gastroesophageal reflux disease (GERD) have symptoms, such as heartburn, but no macroscopic evidence of erosive esophagitis, making symptomatic GERD a common clinical problem in the primary care setting. OBJECTIVE: To compare the efficacy and safety of omeprazole, 20 mg once daily; omeprazole, 10 mg once daily; and placebo in the treatment of symptomatic GERD without erosive esophagitis. METHODS: Patients with a history of heartburn (> or =12 months) and episodes of moderate to severe heartburn on 4 or more of the 7 days before endoscopy were eligible to participate in this 4-week, randomized, double-blind, placebo-controlled trial. The absence of erosive esophagitis was established through endoscopy. Eligible patients were randomized to 1 of 3 treatment groups: omeprazole, 20 mg once daily; omeprazole, 10 mg once daily; or placebo. Patients were assessed at weeks 2 and 4. The efficacy of omeprazole for the treatment of heartburn was determined mainly through the following diary card data: daily resolution of heartburn and complete resolution of heartburn every day during 1 week of treatment. The efficacy of omeprazole for the treatment of acid regurgitation, dysphagia, epigastric pain, and nausea was also assessed. RESULTS: Of 359 randomized patients, 355 were included in the statistical analysis (intention-to-treat population). Daily proportions of patients with no heartburn were consistently greater in the 20-mg omeprazole group (62%, day 7; 74%, day 27) than in the 10-mg omeprazole group (41%, day 7; 49%, day 27) or the placebo group (14%, day 7; 23%; day 27). Complete resolution of heartburn every day during the last treatment week was significantly (P< or =.002) higher in the 20-mg omeprazole group (48%) than in the 10-mg omeprazole (27%) or placebo (5%) group. Omeprazole was significantly (P< or =.003) more effective than placebo for the treatment of acid regurgitation, dysphagia, epigastric pain, and nausea. CONCLUSIONS: Patients with symptomatic GERD require profound acid suppression to achieve symptomatic relief. Omeprazole, 20 mg once daily, was superior to omeprazole, 10 mg once daily, and to placebo in providing early and sustained resolution of heartburn, as well as treatment of other troublesome GERD symptoms.     

Prevention of duodenal ulcer relapse with omeprazole 20 mg daily: A randomized double-blind, placebo-controlled study

Abstract We report the first double-blind, placebo-controlled study that assesses the efficacy and safety of omeprazole 20 mg daily in the maintenance treatment of duodenal ulcer. For the healing phase, 128 patients with endoscopically proven active duodenal ulcer and a history of three or more relapses during the 2 years prior to the study were treated until healing with omeprazole 40 mg daily for 2 and up to 8 weeks. One hundred and twenty-three patients whose ulcers were healed were randomized to receive omeprazole 20 mg daily (n = 60) or placebo (n = 63) for 12 months as maintenance treatment. Patients were interviewed at 3, 6, 9 and 12 months, and endoscopy was performed at 3, 6 and 12 months and whenever symptoms recurred. The healing rates of the 124 patients completing the healing phase were 84, 98 and 100% at 2, 4 and 8 weeks, respectively. During the maintenance phase, eight and four patients discontinued treatment from the omeprazole and placebo groups, respectively. The proportion of patients in remission in the omeprazole group and placebo group after 12 months were 94 and 9% respectively (life table estimates, P < 0.0001). No significant clinical or laboratory changes were observed in patients on therapy with omeprazole. Patients with a history of frequent relapses thus continued to have a very high relapse rate without prophylactic treatment. Omeprazole 20 mg daily was effective and safe in maintaining such patients in remission.     

Double blind cross-over placebo controlled study of omeprazole in the treatment of patients with reflux symptoms and physiological levels of acid reflux--the "sensitive oesophagus".

BACKGROUND: At least 10-15% of patients with reflux symptoms have a normal endoscopy and physiological levels of acid reflux on pH monitoring. Such patients with 50% or more of symptoms associated with acid reflux episodes have "a positive symptom index" (SI), and it has been proposed that this defines the "sensitive oesophagus". AIM: To test the response to omeprazole 20 mg twice daily for four weeks of patients with normal levels of acid reflux using a randomised, placebo controlled, double blind, cross-over design. PATIENTS: Eighteen patients with normal levels of reflux, 12 of whom had a positive SI. METHODS: Response was measured by symptomatic assessment and the SF-36 quality of life (QOL) questionnaire. RESULTS: Patients with a positive SI showed the following improvements on omeprazole compared with placebo: decrease in symptom frequency (p < 0.01), severity (p < 0.01) and consumption of antacids (p < 0.01). In the group with a negative SI only one patient clearly improved. The QOL parameters for bodily pain (65.6 v 53.4, p = 0.03) and vitality (60.6 v 48.8, p = 0.049) were significantly better on omeprazole than placebo for the group overall. CONCLUSION: Omeprazole improves symptoms in 11 of 18 patients with normal endoscopy and pH monitoring, particularly those with a positive SI. This supports the theory that such patients have an oesophagus which is "sensitive" to acid reflux and are part of the GORD spectrum.     

Maintenance Treatment for Gastro-Oesophageal Reflux Disease: A Placebo-Controlled Evaluation of 10 Milligrams Omeprazole Once Daily in General Practice

Background: Gastro-oesophageal reflux disease (GORD) is a frequent cause for consultation in general practice and is a chronically relapsing disease. Methods: This general practice study was a 6-month randomized, double-blind parallel-group placebo-controlled assessment of the efficacy and safety of continuous treatment with 10 mg omeprazole every morning after initial symptom control in 495 patients with GORD but without erosive oesophagitis. Results: On the basis of life-table estimates for cumulative relapse rates, patients in the placebo group (52%) were almost twice as likely as those in the omeprazole group (27%) to discontinue therapy before 24 weeks because of inadequate relief of heartburn or for other reasons including adverse events (all-patients-treated analysis, log rank test, P = 0.0001). Conclusions: This study has shown that 10 mg omeprazole once daily is an effective and well-tolerated treatment strategy in general practice for the long-term management of symptoms of GORD in patients without erosive oesophagitis.     

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.     

Double blind comparison of omeprazole (40 mg od) versus cimetidine (400 mg qd) in the treatment of symptomatic erosive reflux oesophagitis, assessed endoscopically, histologically and by 24 h pH monitoring.

This double blind, double dummy study compares the rate of healing of erosive reflux oesophagitis, assessed endoscopically, with four and eight weeks treatment using omeprazole or cimetidine, and the effect of four and eight weeks treatment of reflux oesophagitis with omeprazole or cimetidine on reflux symptoms, microscopic healing, and in a subgroup of patients, oesophageal pH measurements. Omeprazole 40 mg once daily achieves (i) greater and more rapid symptom relief, (ii) more rapid and sustained endoscopic and histological healing, and (iii) greater reduction of oesophageal acid exposure than cimetidine 400 mg four times daily.     

Long-term management of gastro-oesophageal reflux disease with omeprazole or open antireflux surgery: results of a prospective, randomized clinical trial. The Nordic GORD Study Group

BACKGROUND AND AIM: The efficacy of antireflux surgery (ARS) and omeprazole treatment in the control of gastrooesophageal reflux disease (GORD) are well established. We have compared these two therapeutic options in a randomized, clinical trial. PATIENTS AND METHODS: Three hundred and ten patients with erosive oesophagitis were enrolled into the trial. After a run-in period when all patients had < or = 40 mg of omeprazole daily to heal the oesophagitis and relieve symptoms, 155 patients were randomized to continuous omeprazole therapy and 155 to open antireflux surgery, of whom 144 later had an operation. One hundred and thirty-nine and 129 in the omeprazole and antireflux surgery groups, respectively, completed the 3-year follow-up. Symptoms, 24-h pH monitoring and endoscopy were used to document the outcome. Quality of life was evaluated by the psychological general well-being (PGWB) index and the gastrointestinal symptom rating scale (GSRS). RESULTS: Analysis of time to treatment failure (defined as moderate to severe GORD symptoms for > or = 3 days during the last 7 days, oesophagitis or changed therapy) revealed a significant difference in favour of antireflux surgery (P = 0.0016). Seventeen patients originally submitted to antireflux surgery experienced symptom relapse alone, 14 had oesophagitis at endoscopy and another six had omeprazole for different reasons, leaving 97 patients in clinical remission after 3 years. The corresponding figures in the omeprazole arm were 50 relapses, 18 with oesophagitis, two had surgery, leaving 77 patients in remission. Allowing a dose adjustment in the case of relapse in those on omeprazole therapy to either 40 or 60 mg, the curves describing the failure rates were not significantly different from each other. Quality of life assessment showed a comparable outcome in the two study groups. CONCLUSION: In this randomized multicentre trial we found antireflux surgery to be very efficacious in controlling GORD, a level of control which could also be achieved by omeprazole provided that advantage was taken of the opportunity of adjusting the dose.     

Effects of ranitidine and cisapride on acid reflux and oesophageal motility in patients with reflux oesophagitis: a 24 hour ambulatory combined pH and manometry study.

The effect of ranitidine and cisapride on acid reflux and oesophageal motility was investigated in 18 patients with endoscopically verified erosive reflux oesophagitis. Each patient was treated with placebo, ranitidine (150 mg twice daily), and ranitidine (150 mg twice daily) plus cisapride (20 mg twice daily) in a double blind, double dummy, within subject, three way cross over design. Oesophageal acidity and motility were monitored under ambulatory conditions for 24 hours on the fourth day of treatment, after a wash out period of 10 days during which patients received only antacids for relief of symptoms. Acid reflux was monitored by a pH electrode located 5 cm above the lower oesophageal sphincter. Intraoesophageal pressure was simultaneously recorded from four transducers placed 20, 15, 10, and 5 cm above the lower oesophageal sphincter. Upright reflux was three times higher than supine reflux (median (range) 13.3 (3.7-35.0)% v 3.7 (0-37.6)% of the time with pH < 4.0, p < 0.01, n = 18). Compared with placebo, ranitidine decreased total reflux (from 10.0 (3.2-32.6)% to 6.4 (1.2-22.9)%, p < 0.01), upright reflux (p < 0.05), supine reflux (p < 0.001), and postprandial reflux (p < 0.01), but did not affect oesophageal motility. The combination of ranitidine with cisapride further diminished the acid reflux found with ranitidine--that is, cisapride led to an additional reduction of total reflux (from 6.4 (1.2-22.9)% to 3.7 (1.0-12.7)%, p < 0.01), supine reflux (p < 0.05), and postprandial reflux (p < 0.05). Cisapride also reduced both the number (p<0.01) and duration (p<0.05) of reflux episodes and significantly increased amplitude, duration, and propagation velocity of oesophageal contractions (p<0.05) but did not affect the number of contractions. The findings show that the 30% reduction of oesophageal acid exposure achieved by a conventional dose of ranitidine (150 mg twice daily) can be improved to more than 60% by combination with cisapride (20 mg twice daily). The cisapride induced increase in oesophageal contractile force and propagation velocity seems to enhance the clearance of gastro-oesophageal reflux. Combination of a histamine H2 receptor antagonist with a prokinetic agent may therefore provide an alternative treatment for reflux oesophagitis.     

OMEPRAZOLE AND COMPLICATED GASTRO-OESOPHAGEAL REFLUX DISEASE

Abstract Suppression of acid secretion with omeprazole is highly effective for the healing of oesophagitis. The aims of the present study were to determine whether recovery of gastro-oesophageal reflux disease in patients with stricture improves dysphagia and decreases the dilatation need and to compare the efficacy of omeprazole versus H₂-receptor antagonists. Thirty-eight patients with peptic stricture (grade IV oesophagitis) and erosive oesophagitis underwent endoscopic dilatation and were randomized to omeprazole (40 mg daily; n = 20) versus ranitidine (150 mg twice daily; n=18). Healing was proven endoscopically and patients were interviewed for dysphagia relief. Patients were assessed for relapse by endoscopy 6 months later. The follow-up period was a further 6 months. Patients received maintenance treatment with 40 mg omeprazole daily or ranitidine 150 mg twice daily and the total duration of treatment was 1 year. At 6 months, omeprazole produced a highly significant (P < 0.0001) greater rate of oesophagitis healing and highly significant (P < 0.0001) fewer dilatations compared with H₂-receptor antagonists (18 (90%) patients vs five (28%) patients, respectively; 3.5 vs 9.0 dilatations/patient). At 12 months, not one of the 18 successfully treated patients from the omeprazole group had relapsed. The two remaining patients required further dilatation and 40 and 60 mg omeprazole daily for healing. In comparison, all patients on ranitidine had to undergo further bougienage. In conclusion, omeprazole is a safe and effective maintenance treatment for preventing relapse of complicated reflux oesophagitis.     

Omeprazole 10 Milligrams Once Daily,Omeprazole 20 Milligrams Once Daily,or Ranitidine 150 Milligrams Twice Daily,Evaluated as Initial Therapy for the Relief of Symptoms of Gastro-oesophageal Reflux Disease in General Practice

Background: The efficacy of omeprazole, 20 mg once daily, in the treatment of reflux oesophagitis and the therapeutic advantages over the histamine H₂ receptor antagonists are well documented. This study assessed 20 mg omeprazole daily (OM20), 10 mg omeprazole daily (OM10), and 150 mg ranitidine (RAN) twice daily for symptom relief in gastro-oesophageal reflux disease (GORD). Methods: Patients (n = 994) presenting with heartburn to their general practitioner underwent endoscopy to exclude peptic ulcer disease and were randomized into a UK, multicentre, parallel-group, double-blind comparison of the three treatments for 4 weeks. Symptoms were assessed at clinic visits after 2 and 4 weeks. Results: Symptom relief after 4 weeks was achieved by 61 % (OM20), 49% (OM10), and 40% (RAN) patients (OM20 versus OM10, P < 0.0167; OM20 versus RAN, P < 0.0001; OM10 versus RAN, P < 0.01). Among the patients (32%) with erosive reflux oesophagitis, symptom relief was achieved in 79% (OM20), 48% (OM10), and 33% (RAN) (OM20 versus OM10, P < 0.0001; OM20 versus RAN, P < 0.0001; OM10 versus RAN, NS). Conclusion: Omeprazole, 20 mg, is the most effective initial therapy for relief of GORD symptoms.     

Helicobacter pylori eradication does not exacerbate reflux symptoms in gastroesophageal reflux disease.

BACKGROUND & AIMS: Observational studies have suggested that Helicobacter pylori may protect against gastrointestinal reflux disease (GERD), but these results could be due to bias or confounding factors. We addressed this in a prospective, double blind, randomized, controlled trial. METHODS: H. pylori-positive patients with at least a 1-year history of heartburn with a normal endoscopy or grade A esophagitis were recruited. Patients were randomized to 20 mg omeprazole, 250 mg clarithromycin, and 500 mg tinidazole twice a day for 1 week or 20 mg omeprazole twice a day and identical placebos. A second concurrently recruited control group of H. pylori-negative patients were given open label 20 mg omeprazole twice a day for 1 week. All patients received 20 mg omeprazole twice a day for the following 3 weeks and 20 mg omeprazole once daily for a further 4 weeks. Omeprazole was discontinued at 8 weeks and patients were followed up for a further 10 months. A relapse was defined as moderate or severe reflux symptoms. H. pylori eradication was determined by 13C-urea breath test. RESULTS: The H. pylori-positive cases were randomized to antibiotics (n = 93) or placebo (n = 97). Relapse of GERD occurred in 83% of each of the antibiotic, placebo, and H. pylori-negative groups during the 12-month study period. Life tables revealed no statistical difference between the 2 H. pylori-positive groups (log rank test, P = 0.84) or between the 3 groups (log rank test, P = 0.94) in the time to first relapse. Two patients in each group developed grade B esophagitis at 12 months. CONCLUSIONS: H. pylori eradication therapy does not seem to influence relapse rates in GERD patients.