Management of endoscopy-negative reflux disease: progress with short-term treatment

The efficacy of omeprazole in the treatment of endoscopy-negative reflux disease has been examined in five recently completed, multicentre, double-blind, randomized, parallel group studies. A total of 1959 patients with endoscopy-negative reflux disease took part in these trials in which 20 mg omeprazole once daily (n = 722) was compared with placebo (n = 304) and/or 10 mg omeprazole once daily (n = 624), 150 mg ranitidine twice daily (n = 213), or 10 mg cisapride four times daily (n = 96). In all studies, the primary outcome measures were assessed after 4 weeks of treatment. Absence of heartburn, defined as no episodes of heartburn during the fourth week of treatment, occurred in 14–29% of patients receiving placebo, 31% receiving cisapride, 35% receiving ranitidine, 31–60% receiving 10 mg omeprazole once daily, and 44–62% receiving 20 mg omeprazole once daily. Adequate control of heartburn, defined as only 1 day with episodes of mild heartburn during the seventh week of treatment, occurred in 24% of patients receiving placebo. 46% receiving cisapride, 46% receiving ranitidine, 49–60% receiving 10 mg omeprazole once daily, and 56–63% receiving 20 mg omeprazole once daily, on the basis of data from three of the studies. The differences between the two omeprazole doses and placebo, and between 20 mg omeprazole once daily, and either 10 mg omeprazole once daily, ranitidine or cisapride, were all statistically significant (P < 0.05). Diary cards for most patients who responded to omeprazole showed an absence of heartburn in the first week of treatment. Health-related quality of life was measured at baseline and after 4 weeks of treatment, using validated questionnaires (i.e. the Psychological General Well-Being Index and the Gastrointestinal Symptom Rating Scale). After 4 weeks of treatment, the general well-being of patients taking 10 or 20 mg omeprazole once daily had improved significantly (P < 0.05) compared with those taking placebo. In conclusion, 10 and 20 mg omeprazole once daily provides effective and rapid control of heartburn in patients with endoscopy-negative reflux disease. Absence of heartburn and adequate control of heartburn occur significantly more frequently in patients treated with 20 mg omeprazole once daily, compared with patients treated with 10 mg omeprazole once daily, 150 mg ranitidine twice daily, or 10 mg cisapride four times daily. Omeprazole also restores health-related quality of life, in terms of enhanced well-being, to the level observed in a healthy population.     

Esomeprazole improves healing and symptom resolution as compared with omeprazole in reflux oesophagitis patients: a randomized controlled trial. The Esomeprazole Study Investigators

BACKGROUND: The pharmacologic profile of the new proton pump inhibitor esomeprazole has demonstrated advantages over omeprazole that suggest clinical benefits for patients with acid-related disease. METHODS: 1960 patients with endoscopy-confirmed reflux oesophagitis (RO) were randomized to once daily esomeprazole 40 mg (n=654) or 20 mg (n=656), or omeprazole 20 mg (n=650), the standard recommended dose for RO, for up to 8 weeks in a US, multicentre, double-blind trial. The primary efficacy variable was the proportion of patients healed at week 8. Secondary variables included healing and heartburn resolution at week 4, time to first resolution and sustained resolution of heartburn, and per cent of heartburn-free days and nights. Safety and tolerability were also evaluated. RESULTS: Significantly more patients were healed at week 8 with esomeprazole 40 mg (94.1%) and 20 mg (89.9%) vs. omeprazole 20 mg (86.9%), using cumulative life table estimates, ITT analysis (each P < 0.05). Esomeprazole 40 mg was also significantly more effective than omeprazole for healing at week 4 and for all secondary variables evaluating heartburn resolution. The most common adverse events in all treatment groups were headache, abdominal pain and diarrhoea. CONCLUSION: Esomeprazole was more effective than omeprazole in healing and symptom resolution in GERD patients with reflux oesophagitis, and had a tolerability profile comparable to that of omeprazole.     

Rabeprazole: a review of its use in acid-related gastrointestinal disorders.

Rabeprazole is an inhibitor of the gastric proton pump. It causes dose-dependent inhibition of acid secretion and has a more rapid onset of action than omeprazole. Duodenal ulcers healed faster after treatment with rabeprazole 20 or 40 mg/day than placebo or ranitidine 150 mg 4 times daily and at a generally similar rate to omeprazole 20 mg/day in patients with duodenal ulcers; rabeprazole was similar or superior to these agents in relieving symptoms. Rabeprazole 20 and 40 mg/day healed gastric ulcers faster than placebo, and rabeprazole 20 mg/day healed ulcers at a similar healing rate, to omeprazole 20 mg/day in well controlled 6-week studies. Gastric ulcer symptom relief with rabeprazole was similar or superior to that provided by omeprazole or placebo. In 8-week studies in patients with gastro-oesophageal reflux disease (GERD), rabeprazole 10, 20 and 40 mg/day were more effective than placebo, rabeprazole 20 mg/day was more effective than ranitidine 150 mg twice daily, and rabeprazole 20 mg/day was similar in efficacy to omeprazole 20 mg/day. Symptom relief with rabeprazole in 8-week trials in patients with GERD was superior to that provided by placebo, and similar to ranitidine or omeprazole. Rabeprazole was similar to omeprazole and superior to placebo in both maintenance of healing and prevention of symptoms in patients with healed GERD in 1-year studies. One-week triple therapy with rabeprazole 20 mg twice daily plus 2 antibacterial agents achieved > or = 90% Helicobacter pylori eradication, but, as would be expected, a regimen of rabeprazole 20 mg twice daily plus 1 antibacterial agent was less successful. The drug was as effective as omeprazole and lansoprazole as part of triple therapy for H. pylori eradication. Rabeprazole successfully reduced acid output to target levels and prevented further pathological changes in 10 patients with Zollinger-Ellison syndrome. Usual dosages of rabeprazole are 20 mg/day for 4 weeks to treat duodenal ulcers, 6 weeks for gastric ulcers and 8 weeks for GERD, although some patients with duodenal ulcer may respond to a 10 mg/day dosage. For long term maintenance of GERD healing, 10 or 20 mg daily doses are adequate. Patients with hypersecretory states may need individualised dosages starting at 60 mg/day. The drug was well tolerated in clinical trials, with headache, rash, infection, diarrhoea and flu syndrome as the most common adverse events. In conclusion, rabeprazole appears to be a well tolerated proton pump inhibitor with a rapid onset of action and a low potential for drug interactions. The drug may be used to achieve healing and the relief of symptoms of duodenal ulcer, gastric ulcer and GERD, maintain GERD healing, and can form part of effective regimens to eradicate H. pylori.     

Esomeprazole 20 mg maintains symptom control in endoscopy-negative gastro-oesophageal reflux disease: a controlled trial of 'on-demand' therapy for 6 months

BACKGROUND: Most patients with gastro-oesophageal reflux disease (GERD), regardless of endoscopic status, suffer symptomatic relapse within 6 months of stopping acid suppressant therapy. AIM: To assess the efficacy of 'on-demand' treatment of GERD with esomeprazole, the first proton pump inhibitor developed as an optical isomer. METHODS: In this multicentre, double-blind study, 342 endoscopy-negative GERD patients demonstrating complete resolution of heartburn during the final week of a 4-week treatment period with esomeprazole 20 mg or omeprazole 20 mg once daily were randomized to receive esomeprazole 20 mg or placebo on demand (maximum of one dose per day) for a further 6 months. Use of rescue antacids was permitted. RESULTS: All 342 patients (191 males), aged 19-79 (mean 49) years, were evaluable in the intention-to-treat analysis. The proportion of patients who discontinued treatment due to insufficient control of heartburn was significantly higher among placebo compared to esomeprazole recipients (51% vs. 14%; P < 0.0001). Patients randomized to esomeprazole on-demand therapy remained in the study longer than those in the placebo group (mean 165 vs. 119 days). Over 50% took the study medication for periods of 1--3 consecutive days (esomeprazole) or 4--13 consecutive days (placebo). Use of antacids was > 2-fold higher among placebo recipients. The frequency of adverse events was similar in the two groups, when adjusted for time spent in the study, as were the clinical laboratory profiles. CONCLUSIONS: On-demand therapy with esomeprazole 20 mg is effective and well tolerated in maintaining symptom control in endoscopy-negative GERD.     

Omeprazole is more effective than cimetidine for the relief of all grades of gastro-oesophageal reflux disease-associated heartburn, irrespective of the presence or absence of endoscopic oesophagitis

Background: Previous studies have demonstrated greater efficacy for omeprazole compared with cimetidine in patients with endoscopically verified oesophagitis, but excluded the substantial group of gastro-oesophageal reflux disease (GERD) patients with reflux symptoms but without endoscopic abnormality. This prospective, randomized, double-blind study compared omeprazole and cimetidine in the treatment of GERD-associated heartburn both in patients with symptomatic non-ulcerative oesophagitis and in those with heartburn but without oesophagitis. Methods: A total of 221 patients with heartburn and oesophageal mucosa grade 0 (normal, n = 51), 1 (no macroscopic erosions, n = 52), 2 (isolated erosions, n = 97) or 3 (confluent erosions, n = 21) were randomized to receive double-blind either omeprazole 20 mg daily or cimetidine 400 mg q.d.s. for a period of 4 weeks. Those still symptomatic after 4 weeks of treatment received omeprazole 20 mg daily for a further 4 weeks. Results: There was no correlation between severity of heartburn and endoscopic grade at entry (correlation coefficient = 0.196). After 4 weeks of treatment, the proportion of patients in whom heartburn was controlled (no more than mild symptoms on no more than 1 day in the previous 7) on omeprazole (66%; 74/112) was more than double that on cimetidine (31%; 34/109) (P < 0.0001). There was no significant difference between the relief of heartburn in the 47% of patients without unequivocal oesophagitis (endoscopic grade 0 or 1) and in the 53% of patients with erosive oesophagitis (grade 2 or 3) (P = 0.31). Only treatment with omeprazole (P < 0.0001) and lower severity of heartburn at entry (P < 0.01) were significant in predicting heartburn relief. Amongst those patients requiring an additional 4 weeks of treatment with omeprazole, 67% (54/81) reported that their heartburn was controlled after 8 weeks of treatment. Conclusion: We conclude that omeprazole is superior to cimetidine for the relief of all grades of heartburn in GERD, whether or not the patient has unequivocal endoscopic oesophagitis.     

Lansoprazole heals erosive reflux oesophagitis in patients with Barrett's oesophagus

Background : Barrett's oesophagus is thought to be a complication of severe gastro-oesophageal reflux.
Aim : To determine whether the proton pump inhibitor, lansoprazole, is effective in healing erosive reflux oesophagitis in patients with Barrett's oesophagus.
Methods : An 8-week, randomized, double-blind study was conducted using patients with both erosive reflux oesophagitis and Barrett's oesophagus. Erosive reflux oesophagitis was defined as grades 2–4 oesophagitis; Barrett's oesophagus, as specialized columnar epithelium obtained by biopsy from the tubular oesophagus; and healing, as a return to grade 0 or 1 oesophageal mucosa (complete re-epithelialization). One-hundred and five (105) patients from one centre were randomized to receive either lansoprazole 30 mg daily or ranitidine 150 mg twice daily. Unhealed or symptomatic lansoprazole patients at week 4 were randomized to receive the same 30 mg dose daily or an increased dose of 60 mg daily. Endoscopy was performed at baseline and at weeks 2, 4, 6 and 8.
Results : The treatment groups were similar in regards to baseline characteristics, erosive reflux oesophagitis grades and length of Barrett's oesophagus. At each 2-week interval, lansoprazole patients had significantly greater healing rates and less day and night heartburn and regurgitation than ranitidine patients. There were no significant differences between treatment groups in antacid use, quality of life parameters, or rate of reported adverse events. Median values for fasting serum gastrin levels remained within the normal range for both groups.
Conclusion : In patients with both Barrett's oesophagus and erosive reflux oesophagitis, lansoprazole is significantly more effective than ranitidine in relieving reflux symptoms and healing erosive reflux oesophagitis.     

Systematic review: the efficacy of intermittent and on-demand therapy with histamine H2-receptor antagonists or proton pump inhibitors for gastro-oesophageal reflux disease patients

AIM: To perform a systematic review on the efficacy of intermittent and on-demand therapy with either histamine H2-receptor antagonists or proton pump inhibitors for patients with erosive oesophagitis or symptomatic heartburn. METHOD: We conducted randomized-controlled trials of non-continuous therapy in gastro-oesophageal reflux disease patients. RESULTS: Fourteen studies met inclusion criteria. Because of variation in outcome measures statistical pooling of results was not possible. Results were analysed qualitatively. Four studies evaluated intermittent therapy of treatment 3 days a week with omeprazole 20 mg or daily with ranitidine which were not efficacious compared to a daily proton pump inhibitor. Famotidine 10 and 20 mg, ranitidine 75 mg and cimetidine 200 mg were efficacious in five on-demand studies for relief of symptomatic heartburn episodes. In three of four studies, evaluating only non-erosive (endoscopy-negative) gastro-oesophageal reflux disease patients, esomeprazole 20 and 40 mg and omeprazole 10 and 20 mg a day were efficacious using willingness to continue as an endpoint. Lansoprazole 30 mg and omeprazole 20 mg maintained symptom control in 60-70% of healed oesophagitis patients. CONCLUSIONS: Intermittent proton pump inhibitor or H2-receptor antagonist therapy is not effective in maintaining control in oesophagitis patients. H2-receptor antagonists are effective for relief of heartburn episodes. On-demand proton pump inhibitor therapy may work in a proportion of non-erosive gastro-oesophageal reflux disease patients.     

Omepmazole or high-dose ranitidine in the treatment of patients with reflux oesophagitis not responding to ''standard doses''of H2-receptor antagonists

Ninety-eight patients (26 females), who presented with erosive and/or ulcerative oesophagitis, despite at least a 3-month period of treatment with standard doses of cimetidine (greater than or equal to 1200 mg daily) or ranitidine (greater than or equal to 300 mg daily), were included in a double-blind, randomized trial to compare omeprazole (40 mg o.m.) with a high dose of ranitidine (300 mg b.d.). The treatment was given for 4-12 weeks; endoscopy assessment and laboratory screening were performed on entry to the trial and thereafter every fourth week. Endoscopic healing was defined as complete epithelialization of all macroscopic erosions or ulcers in the squamous epithelium. An 'intention-to-treat' analysis of the clinical data revealed omeprazole to be superior to ranitidine: 63% of those patients who were given omeprazole were healed endoscopically after a 4-week period of treatment, compared with only 17% of those given ranitidine. This difference in healing rate persisted during the 12-week study period (90% vs 47% after 12 weeks; P less than 0.0001). Reflux symptoms were more rapidly and completely relieved with omeprazole: heartburn resolved completely in 86% of patients treated with omeprazole for 4 weeks compared with 32% in the ranitidine group (P less than 0.0001). The mean basal gastrin concentrations increased only in those given omeprazole from 18.9 pmol/L at pre-entry to a mean value of 31.7 pmol/L on the last day of omeprazole administration. In ranitidine-treated patients no significant increase in basal gastrin concentration was observed. Both drugs were well tolerated with few adverse events, which were mainly mild and transient. These results demonstrate the superiority of omeprazole over a high dose of ranitidine in the treatment of resistant reflux oesophagitis.     

An evaluation of increasing doses of ranitidine for treatment of heartburn

BACKGROUND: This was a randomized, double-blind, placebo-controlled, multicentre, parallel group, dose-ranging trial of ranitidine tablets for relief of episodic heartburn. Adult out-patients who reported heartburn relieved by antacids at least seven times per week were eligible. METHODS: Patients who successfully completed a 1-week single-blind placebo run-in phase and who did not achieve adequate relief in more than 50% of heartburn episodes were randomized to a 1-week, double-blind treatment phase during which they received ranitidine doses of 25, 75 or 125 mg, or placebo. RESULTS: Of 577 patients randomized, 566 had at least one evaluable heartburn episode and were included in the intention-to-treat analysis. All three ranitidine doses were statistically significantly superior to placebo in providing overall episodic heartburn relief for the first episode (P < 0.002), last episode (P相似文献   

Lansoprazole versus ranitidine for the treatment of reflux oesophagitis

Background: Lansoprazole is a H⁺, K⁺-ATPase (proton pump) inhibitor with an anti-secretory action and is therefore potentially useful in the treatment of gastro-oesophageal reflux. Methods: This study was conducted to determine the efficacy and short-term safety of lansoprazole at doses of 30 mg or 60 mg once daily, compared with ranitidine 150 mg twice daily, in the treatment of patients with reflux oesophagitis. This was a double-blind, stratified, randomized, comparative, parallel group study conducted in five centres in the UK. A total of 229 patients (155 men) aged 18–79 years with endoscopically-confirmed oesophagitis were randomized to receive lansoprazole 30 mg p.o. daily, lansoprazole 60 mg p.o. daily, or ranitidine 150 mg p.o. b.d. Efficacy was assessed by endoscopic examination at 4 weeks and 8 weeks, together with symptom relief and antacid usage. Results: Lansoprazole 30 mg and 60 mg were superior at 4 and 8 weeks (P < 0.01) to ranitidine in healing reflux oesophagitis: respective healing rates being 84%, 72% and 39% after 4 weeks and 92%, 91% and 53% after 8 weeks. Relief of heartburn with lansoprazole 30 mg and 60 mg was superior to that achieved with ranitidine at both week 4 (P < 0.01) and week 8 (P < 0.02). Sixty-four patients experienced a total of 85 adverse events, one-third of which were considered drug-related. The incidence and severity were similar in the three groups. Conclusion: Lansoprazole 30 mg and 60 mg once daily are more effective than ranitidine 150 mg twice daily in the short-term treatment of reflux oesophagitis.     

Daily omeprazole surpasses intermittent dosing in preventing relapse of oesophagitis: a US multi-centre double-blind study

Introduction: Relapse of erosive oesophagitis occurs in almost all patients if treatment is stopped after initial healing. Aim: To assess the potential of different therapeutic regimens of omeprazole to prevent relapse of erosive reflux oesophagitis after initial healing with omeprazole. Patients and methods: Patients whose active erosive reflux oesophagitis (grade 2) had healed (grade 0 or 1) after 4–8 weeks of open-label omeprazole 40 mg daily (phase I) were eligible to join a multi-centre, 6-month double-blind, placebo-controlled maintenance study (phase II), which included endoscopy, symptom assessments, serum gastrin measurements, and gastric fundic biopsies. During phase I, endoscopy was performed at weeks 0, 4, and 8. At the end of phase I, 429 of 472 patients (91%) were healed, and there were significant reductions in heartburn, dysphagia and acid regurgitation. Of the 429 patients who healed, 406 joined phase II and were randomized to one of three groups: 20 mg omeprazole daily (n=138), 20 mg omeprazole for 3 consecutive days each week (n=137), or placebo (n=131). During phase II, endoscopy was performed at months 1, 3, and 6 or at symptomatic relapse. Results: The percentages of patients still in endoscopic remission at 6 months were 11% for placebo, 34% for omeprazole 3-days-a-week, and 70% for omeprazole daily. Both omeprazole regimens were superior to placebo in preventing recurrence of symptoms (P<0.001); however, omeprazole 20 mg daily was superior to omeprazole 20 mg 3-days-a-week (P<0.001). Compared to baseline, omeprazole therapy resulted in no significant differences among treatment groups in the distribution of gastric endocrine cells. Conclusions: These results show that after healing of erosive oesophagitis with 4–8 weeks of omeprazole, relapse of oesophagitis and recurrence of reflux symptoms can be prevented in 70% of patients with a maintenance regimen of 20 mg daily, but that intermittent dosing comprising 3 consecutive days each week significantly compromises efficacy.     

Omeprazole 40 mg once a day is equally effective as lansoprazole 30 mg twice a day in symptom control of patients with gastro-oesophageal reflux disease (GERD) who are resistant to conventional-dose lansoprazole therapy-a prospective, randomized, multi-centre study

BACKGROUND: Comparative studies of omeprazole and lansoprazole are scarce and even scarcer are comparisons of higher doses. Most of the comparative studies have assessed the effect of the two proton pump inhibitors (PPIs) on gastric acid secretion or gastric pH. Few studies have compared clinical end-points such as oesophageal healing and symptom control. AIM: To determine the clinical efficacy of omeprazole 40 mg daily as compared to lansoprazole 30 mg twice a day in symptom control of patients with severe symptomatic GERD. METHODS: Ninety-six patients who failed a standard dose of lansoprazole (30 mg once daily), were enrolled in a prospective fashion from three VA medical centres and were randomized to receive 6 weeks of either omeprazole 40 mg daily or lansoprazole 30 mg twice daily. Patients reported daily on symptom severity and frequency, antacid consumption and side-effects. RESULTS: Forty-six patients received omeprazole and 44 lansoprazole. Although not statistically significant, there was a consistent trend of better symptom control in the omeprazole group for daytime and night-time heartburn and acid regurgitation. There was no statistical difference between the two groups in mean antacid consumption overall and at the end of each of the 6 weeks of the study. In addition, there was no significant difference in the overall frequency of side-effects between the two groups nor for each individual side-effect. CONCLUSION: Omeprazole 40 mg once daily is equally effective and tolerated as lansoprazole 30 mg twice daily in symptom control of patients with GERD.     

Double-blind, placebo-controlled comparison of rabeprazole 20 mg vs. omeprazole 20 mg in the treatment of erosive or ulcerative gastro-oesophageal reflux disease

Background:

Rabeprazole sodium is the most recent member of a class of substituted benzimidazole molecules known as proton pump inhibitors. Other proton pump inhibitors have been shown to be effective in healing oesophagitis.

Methods:

In this randomised, double-blind, multicentre study, conducted at 27 European sites, the efficacy and safety of rabeprazole and omeprazole were compared in patients with erosive or ulcerative gastro-oesophageal reflux disease (GERD).100 patients received rabeprazole 20 mg, and 102 patients omeprazole 20 mg once daily for 4 or 8 weeks, with healing monitored by endoscopy.

Results:

Overall GERD healing rates observed and evaluated at weeks 4 and 8 were equivalent. Four-week healing rates for rabeprazole and omeprazole were 81%–81% and 92%–94% for 8-week healing. Rabeprazole-treated patients had similar relief of the frequency and intensity of heartburn to those treated with omeprazole. Both drugs were well tolerated over the 8-week treatment period. Mean changes in fasting serum gastrin were comparable. No significant differences in laboratory parameters were seen. Biopsies for argyrophil ECL cell histology at the end-point revealed a similar distributions of hyperplasia grades to those at baseline in both groups. Biopsies of body and antral mucosa for other parameters were similar between treatments for Helicobacter pylori colonization, presence or degree of inflammation, atrophy or intestinal metaplasia at the end-point.

Conclusion:

In this study, GERD healing rates following rabeprazole 20 mg once daily were equivalent to those obtained with omeprazole 20 mg once daily. Both treatments resulted in a comparable relief of the frequency and intensity of heartburn associated with this disease, and both were well tolerated.

     

The role of acid suppression in patients with endoscopy-negative reflux disease: the effect of treatment with esomeprazole or omeprazole

BACKGROUND: Patients with endoscopy-negative reflux disease have reflux symptoms, mainly heartburn, but not mucosal breaks characteristic of erosive oesophagitis. Standard-dose proton pump inhibitors can provide symptom relief in endoscopy-negative reflux disease but the effect of greater acid suppression has not been studied. AIM: To test the hypothesis that esomeprazole produces heartburn resolution in a greater proportion of patients with ENRD than omeprazole. METHODS: Three multi-centre randomized, controlled, double-blind, 4-week acute treatment studies were conducted in endoscopy-negative reflux disease patients. In study A (n = 1282), patients received either esomeprazole 40 mg, esomeprazole 20 mg or omeprazole 20 mg daily; in studies B (n = 693) and C (n = 670) patients received either esomeprazole 40 mg or omeprazole 20 mg (B), and esomeprazole 20 mg or omeprazole 20 mg (C), respectively. RESULTS: Resolution of heartburn at 4 weeks (no heartburn symptoms during the last 7 days) was achieved in similar proportions of patients in each treatment arm in study A (esomeprazole 40 mg, 56.7%; esomeprazole 20 mg, 60.5%; omeprazole 20 mg, 58.1%), study B (esomeprazole 40 mg, 70.3%; omeprazole 20 mg, 67.9%) and study C (esomeprazole 20 mg, 61.9%; omeprazole 20 mg, 59.6%). There were no significant differences between treatment groups within each study. CONCLUSIONS: More than 60% of endoscopy-negative reflux disease patients reported heartburn resolution but, after 4 weeks of therapy, these proportions did not differ significantly between treatments.     

Bedtime ranitidine does not eliminate the need for a second daily dose of omeprazole to suppress nocturnal gastric pH

BACKGROUND: We have previously shown that 70% of patients experience nocturnal gastric acid breakthrough (defined as pH<4 for more than 60 min between 22.00 and 06.00 hours) on twice a day (b.d.) proton pump inhibitor. Adding 150 or 300 mg of ranitidine at bedtime is more effective than additional omeprazole at bedtime in control of night-time acid breakthrough. AIM: To assess whether omeprazole 20 mg AM plus ranitidine 150 mg HS would be as effective as omeprazole 20 mg before breakfast and dinner (b.d. AC) in intragastric pH control, particularly during the overnight period. METHODS: Twenty healthy volunteers (11 males, 9 females, mean age 32.7 years) were treated with omeprazole (OME) 20 mg b.d. AC and placebo HS or omeprazole 20 mg AM and placebo before dinner plus ranitidine (RAN) 150 mg HS for 7 days, in a randomized, double-blind, crossover design, with a 1 week washout between study periods. On day 8 subjects were monitored for 24 h with a single channel pH probe placed in the stomach 10 cm below the proximal border of the LES. Percentage time pH<4 for total, upright and recumbent positions were compared between the two regimens using Wilcoxon matched pairs testing. RESULTS: Expressed in median values of percentage time pH<4: upright time intragastric pH<4 on OME 20 mg b.d. AC was 18.9 compared to 29.7 on OME AM + RAN HS (P = 0.003). Recumbent time pH<4 on OME 20 mg b.d. AC was 23.45 compared to 44.75 on OME AM + RAN HS (P = 0.02). CONCLUSION: Bedtime ranitidine does not eliminate the need for an evening dose of omeprazole to control intragastric pH in patients requiring more than a single daily dose of omeprazole.     

Efficacy of esomeprazole 40 mg vs. lansoprazole 30 mg for healing moderate to severe erosive oesophagitis

BACKGROUND: Secondary analyses from previous studies indicated that esomeprazole was more effective than lansoprazole and omeprazole in healing moderate or severe (Los Angeles grades C or D) erosive oesophagitis (EE). AIM: To compare prospectively healing rates with esomeprazole vs. lansoprazole in patients with moderate to severe EE. METHODS: In this multicentre, randomized, double-blind, parallel-group trial, adult patients with endoscopically confirmed moderate or severe EE received esomeprazole 40 mg (n = 498) or lansoprazole 30 mg (n = 501) once daily for up to 8 weeks. The primary end point was EE healing through week 8. Secondary assessments included investigator-assessed resolution of symptoms and safety and tolerability. RESULTS: Time to healing was significantly different (P = 0.007), favouring esomeprazole. Estimated healing rates at week 8 were 82.4% with esomeprazole 40 mg and 77.5% with lansoprazole 30 mg. Heartburn resolved at week 4 in 72% and 64% of patients who received esomeprazole and lansoprazole, respectively (P = 0.005). Control of other GERD symptoms was similar between treatments. Both treatments were well tolerated. CONCLUSIONS: With 8 weeks' treatment, esomeprazole 40 mg once daily heals moderate to severe EE faster and in more patients, and resolves heartburn in more patients after 4 weeks of treatment, than lansoprazole 30 mg once daily.     

Effects of ranitidine, given t.d.s., on intragastric and oesophageal pH in patients with gastrooesophageal reflux

The purpose of this study was to determine the effects of 150 mg ranitidine, 300 mg ranitidine or placebo, administered every 8 h, on gastro-oesophageal pH and heartburn parameters in reflux patients. Twelve symptomatic reflux patients received each of the three treatments in a randomized, double-blind, crossover fashion. Intragastric and oesophageal pH were monitored continuously for a 24 h period. Meals were standardized, consumed at set times and patients were allowed to recline and sleep from 23.00 hours until 06.00 hours only. The gastric record was analysed for the percentage of time that the pH was greater than or equal to 4. The oesophageal record was analysed for acid contact time (percentage time (%) pH less than or equal to 4.0) and reflux episode frequency. Finally, patients recorded each new episode of heartburn and graded daytime heartburn severity at the end of each hour. Ranitidine increased the median (%) time that the intragastric pH remained at or above 4, from 4.5 (placebo) to 33.9% (150 mg dose) and 33.3% (300 mg dose). Ranitidine dose-dependently reduced the median 24-hour oesophageal acid contact time from 13.3% (placebo) to 6.8% (150 mg dose) and 2.5% (300 mg dose). The 300 mg dose significantly reduced daytime heartburn episode frequency and severity while the 150 mg dose reduced heartburn severity only. We conclude that 150 and 300 mg doses of ranitidine administered every 8 h have major, sometimes dose-dependent effects on the objective parameters and symptoms of gastro-oesophageal reflux.     

Omeprazole or ranitidine plus metoclopramide for patients with severe erosive oesophagitis. A cost-effectiveness analysis

The objective of this study was to evaluate the clinical and economic effects of 2 clinical strategies for treating severe (grade II and above) erosive oesophagitis or poorly responsive gastro-oesophageal reflux disease. A single-blind, randomised controlled trial of up to 8 weeks' duration was undertaken comparing omeprazole with ranitidine plus metoclopramide in patients with severe and symptomatic erosive oesophagitis (endoscopic grade II and above). Two cost-effectiveness ratios were calculated: cost per healed patient and cost per symptom-free day. The study perspective was that of the payer or insurer of medical care. Healing rates were significantly higher among omeprazole-treated patients than among those who received ranitidine/metoclopramide at 4 weeks (68.5% vs 30.4%; p < 0.01) and overall (81.5% vs 45.7%; p < 0.01). Overall, mean gastrointestinal-related direct medical costs per healed patient were lower for the omeprazole group ($US189.60) than for the ranitidine/metoclopramide group ($US319.28). The incremental cost of an additional cure with omeprazole compared with ranitidine/metoclopramide was $US24.05. The overall average cost per symptom-free day was lower in the omeprazole group ($US7.88) than in the ranitidine/metoclopramide group ($US10.81). The incremental cost to obtain an additional symptom-free day with omeprazole, compared with ranitidine/metoclopramide, was $US1.41. In conclusion, superior efficacy at comparable cost is achieved by omeprazole compared with ranitidine/metoclopramide in the treatment of patients with severe erosive oesophagitis.     

Omeprazole is more effective than cimetidine in the prevention of recurrence of GERD-associated heartburn and the occurrence of underlying oesophagitis

Background:

There is documentation of the long-term use of omeprazole 10 mg o.d. in patients with reflux oesophagitis but not in the large number of gastro-oesophageal reflux disease (GERD) patients without oesophagitis. There is also a paucity of data on the long-term use of cimetidine in GERD patients.

Methods:

One hundred and fifty-six patients (100 male) who previously had symptomatic non-ulcerative oesophagitis (81%) or symptoms without oesophagitis (19%), were recruited. All patients were in symptomatic remission following 4 weeks of omeprazole 20 mg o.d. or cimetidine 400 mg q.d.s. and, if required, a further 4 weeks of omeprazole 20 mg o.d. Patients were randomized to receive, double-blind, either omeprazole 10 mg o.m. (n = 77) or cimetidine 800 mg nocte (n = 79) for 24 weeks.

Results:

A greater proportion of patients receiving omeprazole, compared with cimetidine, were in symptomatic remission after 12 (69 vs. 27%) and 24 weeks (60 vs. 24%) (each P < 0.0001). The median time to symptomatic relapse was longer for patients receiving omeprazole (169 vs. 15 days) (P = 0.0001). Of patients leaving the study in symptomatic remission, a greater proportion receiving omeprazole, compared with cimetidine, was free of oesophagitis (84 vs. 53%) (P < 0.05).

Conclusion:

Omeprazole 10 mg o.m. is more effective than cimetidine 800 mg nocte in the prevention of recurrence of GERD-associated heartburn and the occurrence of underlying oesophagitis.

     

Pantoprazole provides rapid and sustained symptomatic relief in patients treated for erosive oesophagitis

BACKGROUND: Effective symptom control is a primary concern of most heartburn suffers. AIM: To compare the safety and efficacy of pantoprazole, placebo and the H2 antagonist nizatidine in relieving symptoms in patients with erosive oesophagitis. METHODS: Data from two randomized, double-blind studies were pooled. Patients received pantoprazole 10, 20 or 40 mg, or placebo daily (study 1, n = 603), or pantoprazole 20 or 40 mg daily or 150-mg nizatidine b.d. (study 2, n = 243) for either 4 or 8 weeks. Endoscopy was performed at baseline, week 4 and week 8. Persistent absence of symptoms was defined as the first day that no symptoms were reported by the patient on that day or any subsequent study day. RESULTS: A significantly higher percentage (P < 0.05) of pantoprazole patients reported elimination of all symptoms by week 8. Daytime heartburn, night-time heartburn and regurgitation were significantly better controlled with pantoprazole (with a dose-response at most time-points). Absence of symptoms was a powerful predictor of healing; presence of symptoms correlated poorly. CONCLUSION: Pantoprazole is more effective than placebo or nizatidine for controlling heartburn and acid regurgitation in patients with erosive oesophagitis. Relief of GERD symptoms is highly predictive of healing of erosive oesophagitis at 4 and 8 weeks.