Cisapride for Gastroesophageal Reflux Disease: A Placebo-Controlled, Double-Blind Study

Objectives : To evaluate the safety and efficacy of cisapride in patients with gastroesophageal reflux disease. Methods : Patients (N = 177) were randomized to double-blind treatment with cisapride (10 or 20 mg q.i.d .) or placebo for 12 wk. Efficacy was determined by pre- and poststudy endoscopies, symptom assessments by patient and physician, and Maalox consumption. Safety evaluations included vital signs, electrocardiograms, clinical laboratory tests, and reports of adverse events. Results : Cisapride 10 ing significantly reduced daytime and nighttime heartburn at 4 wk compared with placebo. Cisapride 20 mg reduced both daytime and nighttime heartburn at 4, 8, and 12 wk, compared with placebo, and was also significantly superior to the 10-mg dose at 12 wk. The percent of patients with endoscopic healing was significantly higher with cisapride 20 mg than with placebo [healing: 51 vs 36% ( p ≤ 0.044)1. Maalox usage declined significantly with cisapride 20 mg compared with placebo. No clinically significant changes in safety variables occurred with cisapride. The most frequently reported adverse events in the cisapride group were diarrhea, headache, and sinusitis. Conclusions : Cisapride 10 and 20 mg q.i.d . were safe and well tolerated in a population of patients with mild-to-moderate gastro-esophageal reflux disease. Both symptoms and endoscopic grade improved after 12 wk of treatment with cisapride 20 mg q.i.d .     

Nizatidine versus placebo in gastroesophageal reflux disease

In a randomized, multicenter trial, nizatidine 150 mg or 300 mg, or placebo, was administered twice daily for six weeks to 515 patients with gastroesophageal reflux disease (GERD). Gelusil antacid tablets were taken as needed for pain. Significantly superior rates of endoscopically proven complete healing (normal-appearing mucosa) versus placebo occurred after three weeks with nizatidine 150 mg, and after six weeks with nizatidine 300 mg. Six-week healing rates were 38.5% for nizatidine 300 mg, 41.1% for nizatidine 150 mg, and 25.8% for placebo. The nizatidine 150 mg treatment group had significantly greater improvement in daytime and nighttime heartburn severity after one day of therapy versus placebo. Twice-daily administration of nizatidine 150 mg or 300 mg provides prompt relief from the major symptom of GERD, heartburn, and complete healing of esophagitis is seen in many patients.     

Effect of esomeprazole on nighttime heartburn and sleep quality in patients with GERD: a randomized, placebo-controlled trial

OBJECTIVES: Sleep disturbances are common in patients with gastroesophageal reflux disease (GERD). This study examined the effects of esomeprazole on nighttime heartburn, GERD-related sleep disturbances, sleep quality, work productivity, and regular activities. METHODS: This multicenter, randomized, double-blind, placebo-controlled trial included adults with GERD-associated sleep disturbances and moderate-to-severe nighttime heartburn (recorded by patient diary during screening). Patients received oral esomeprazole 40 mg (n = 220) or 20 mg (n = 226) or placebo (n = 229) once daily for 4 wk. The primary outcome was relief of nighttime heartburn. Secondary outcomes included resolution of sleep disturbances, sleep quality measured by the Pittsburgh Sleep Quality Index (PSQI) questionnaire, and work productivity measured by the Work Productivity and Activity Impairment Questionnaire. RESULTS: Nighttime heartburn was relieved in 53.1% (111/209), 50.5% (111/220), and 12.7% (28/221) of patients who received esomeprazole 40 mg, esomeprazole 20 mg, and placebo, respectively. Differences (95% CI) versus placebo were 40.5% (32.4%, 48.5%) and 37.8% (29.9%, 45.7%) and were highly significant (p < 0.0001). GERD-related sleep disturbances resolved in significantly more (p < 0.0001) patients who received esomeprazole 40 (73.7%) or 20 mg (73.2%) than in those who received placebo (41.2%). Both esomeprazole groups had greater PSQI global score changes from baseline (p < 0.0001 vs placebo) and more (p < 0.0001 vs placebo) work hours saved per week per patient compared with baseline (esomeprazole 40 mg, 11.6 h; esomeprazole 20 mg, 12.3 h; placebo, 6.2 h). CONCLUSIONS: Esomeprazole reduced nighttime heartburn and GERD-related sleep disturbances and improved sleep quality and work productivity.     

Metoclopramide in Gastroesophageal Reflux Disease: Rationale for its Use and Results of a Double-Blind Trial

We investigated the acute effect of metoclopramide on lower esophageal sphincter pressure, esophageal contraction amplitude, and gastric emptying and compared metoclopramide, 10 mg four times a day, to placebo in improving the symptoms and objective parameters of reflux esophagitis in 19 patients in a randomized, double-blind 4-wk outpatient trial. Orally administered metoclopramide, 10 mg, significantly accelerated gastric emptying of a semisolid meal in patients in whom it was delayed; lower esophageal sphincter pressure was significantly increased for up to 90 min, but there were no changes in esophageal contraction amplitude. During the treatment trial, metoclopramide resulted in an overall improvement in heartburn and regurgitation of 60%, significantly better than 32% improvement after placebo (p less than 0.05). Compared to baseline symptoms scores, metoclopramide significantly improved both daytime and nighttime heartburn and regurgitation. Compared to placebo-treated patients, the metoclopramide group had significantly fewer episodes of daytime heartburn and regurgitation (p less than 0.05), while nighttime symptoms significantly improved with both treatments. Mean antacid consumption was significantly reduced by metoclopramide, 61%, compared to placebo-treated patients, 21% (p less than 0.05), who were ingesting a mean of 1.9 oz of antacid daily. Endoscopic and histological improvement were similar in both groups, although histological healing occurred in three patients after metoclopramide compared with none in the placebo group. Our data suggest that: 1) gastric emptying and lower esophageal sphincter pressure were significantly improved by acute administration of oral metoclopramide; 2) metoclopramide therapy for 4 wk is significantly more effective than placebo (medium dose antacid therapy) in relieving the symptoms of gastroesophageal reflux without significantly altering objective parameters of esophagitis; 3) metoclopramide effectively addresses the diffuse upper gastrointestinal motor disturbances present in reflux esophagitis patients.     

Rabeprazole in nonerosive gastroesophageal reflux disease: a randomized placebo-controlled trial

OBJECTIVES: Clinical results to date suggest that antisecretory therapy may be less effective in providing symptom relief for patients with nonerosive gastroesophageal reflux disease (GERD) than for patients with erosive disease. This study was carried out to assess the efficacy and rapidity of once-daily rabeprazole (10 mg or 20 mg) in relieving symptoms in endoscopically negative patients with moderately severe GERD symptoms and to evaluate the safety of these doses over 4 wk. METHODS: This placebo-controlled, double blind study enrolled 203 men and women with moderately severe symptoms of GERD. After a 2-wk, single-blind placebo run-in phase, patients were randomized to receive 10 mg or 20 mg of rabeprazole or placebo once daily for 4 wk. RESULTS: Rabeprazole rapidly and effectively relieved heartburn, with significant improvements on day 1 of dosing. It also improved most other GERD-related symptoms, including regurgitation, belching, bloating, early satiety, and nausea. Both rabeprazole doses were significantly superior to the placebo with respect to time to the first 24-h heartburn-free interval (2.5 and 4.5 days for 10 mg and 20 mg of rabeprazole, respectively, vs 21.5 days for the placebo) and first daytime or nighttime heartburn-free interval (1.5-3 days for rabeprazole groups vs 12.5-15 days for the placebo), as well as to percentage of time patients were heartburn-free and free of antacid use. Both rabeprazole doses were well tolerated. CONCLUSIONS: Based on these findings and prior studies, rabeprazole reliably relieves GI symptoms equally well in both nonerosive GERD and erosive GERD.     

Assessment by prolonged ambulatory manometry of the effect of oral cisapride on proximal small bowel inter-digestive motility

The effects of cisapride, given orally at standard therapeutic dosage (10 mg tds), on proximal small bowel interdigestive motility in ten healthy volunteers was assessed by prolonged ambulatory manometry. Cisapride did not alter the duration of the MMC cycle, duration of phase II or the propagation rate of phase III in either the daytime or nighttime periods. However, when compared to studies, in which subjects received no drug, both nighttime and daytime phase II mean contractile amplitude, but not contractile incidence, were significantly increased (P0.001) by cisapride. Cisapride significantly increased the incidence of distally propagated clustered activity. We conclude that the major effects of cisapride on healthy small bowel motor function is to increase the mean contractile amplitude and incidence of distally propagated clustered activity.Part of this work was presented to the American Gastroenterological Association during Digestive Disease Week in New Orleans, 1991.     

On-demand therapy with pantoprazole 20 mg as effective long-term management of reflux disease in patients with mild GERD: the ORION trial

AIMS: To compare safety and efficacy of on-demand pantoprazole 20 mg/40 mg versus placebo in the long-term management of patients with mild gastroesophageal reflux disease (GERD) after heartburn relief. METHODS: A total of 634 patients with endoscopically confirmed GERD grade 0/I and heartburn were included. During the acute phase, patients were treated with pantoprazole 20 mg once daily for 4 weeks. Those patients relieved from heartburn entered the long-term phase, and were randomly assigned to either treatment group pantoprazole 20 mg, 40 mg or placebo. Over 6 months, patients took study medication on demand (antacids as rescue medication) and discontinued the drug once symptoms abated. RESULTS: After 4 weeks a total of 87.1%/90.0% of patients were free of heartburn (ITT/PP), and entered the subsequent long-term phase. The perceived average daily symptom load (placebo: 3.93, pantoprazole 20 mg: 2.91, pantoprazole 40 mg: 2.71, ITT) and the number of antacid tablets taken (average number, placebo: 0.68, pantoprazole 20 mg: 0.45, pantoprazole 40 mg: 0.33, ITT) were significantly higher in the placebo than in both pantoprazole groups (p<0.0001), with no statistically significant difference between the two pantoprazole groups. The discontinuation rate due to insufficient control of heartburn was significantly lower in both pantoprazole groups compared to placebo (placebo: 10.9, pantoprazole 20 mg: 2.8, pantoprazole 40 mg: 0.9, ITT). CONCLUSIONS: Our findings favor on-demand treatment with pantoprazole 20 mg for the long-term management of heartburn in patients with uncomplicated GERD (grade 0/I) with superiority to placebo.     

Cisapride versus placebo in reflux esophagitis. A multicenter double-blind trial

In a 6 to 12-week double-blind trial, the effect of cisapride (10 mg q.i.d.) was compared with that of placebo in 63 patients with esophagitis confirmed by endoscopy and/or biopsy. In only one patient (3%) in the cisapride group but in 43% of the placebo patients (p = 0.001), symptoms had not improved after 6 weeks. Forty patients continued treatment until week 12. At that time, control endoscopy showed a significantly (p = 0.005) higher rate of healing (no erosions, ulcers, or bleeding mucosa) in the cisapride patients (63%) than in the placebo patients (12%). At week 12, only three of the 21 cisapride patients still had moderate reflux symptoms, whereas eight of the 19 placebo patients had moderate or severe symptoms (p less than 0.05). Cisapride patients also took significantly (p less than 0.001) less antacids during the trial. These results show that cisapride, 10 mg q.i.d., heals esophagitis lesions and greatly reduces associated symptoms. The treatment was well tolerated.     

Effect of cisapride on functional dyspepsia in patients with and without histological gastritis: A double-blind placebo-controlled trial

In the present double-blind placebo-controlled study the effect of cisapride on functional dyspepsia was evaluated in patients with and without histological gastritis. Patients with functional dyspepsia and whose symptoms persisted after a 2 week run-in period with antacid treatment were randomized to receive cisapride (10 mg) or matching placebo three times daily for 4 weeks. Symptoms of epigastric pain, bloating, nausea, belching, early satiety and heartburn were graded on a four-point scale based on patients’ feedback and diary card recording. A global response was also formulated by the investigators. One hundred and four patients entered the study and 76 completed the trial, comprising 36 patients with histological gastritis and 40 patients without gastritis. Symptom scores in both gastritis and non-gastritis groups were significantly improved by both cisapride and placebo; however, the improvement was not statistically different between the two treatment groups. Cisapride produced a good or better global response in 58% of subjects with histological gastritis and in 53% of subjects without gastritis compared with 47% and 52%, respectively, of patients on placebo; this difference was not statistically significant. Gastric histology did not influence the effect of cisapride on the symptoms of functional dyspepsia.     

Treatment of chronic constipation with cisapride and placebo.

The effect of cisapride (20 mg bid), a new prokinetic drug, on bowel habits and laxative consumption was studied in patients with idiopathic painless constipation and chronic laxative intake. After a four week base line period, spontaneous defection (frequency without laxative intake) and total defecation (total frequency) were measured. Patients with a spontaneous defecation of less than three stools per week entered the treatment period and were randomly assigned to double blind treatment with either cisapride (n = 64) or placebo (n = 62). After eight weeks of treatment, a four week run out phase on single blind placebo medication was conducted. Cisapride and placebo increased spontaneous stool frequency from 1.1 +/- 0.2 SEM to 3.0 +/- 0.2 per week (p less than 0.001) and from 1.2 +/- 0.1 to 1.5 +/- 0.2 (p greater than 0.05), respectively. Laxative consumption was decreased from 3.6 +/- 0.3 to 1.8 +/- 0.2 doses/week by cisapride (p less than 0.001) and from 3.3 +/- 0.3 to 2.8 +/- 0.3 by placebo (p less than 0.05). Both drugs improved constipation as assessed by the patient by means of a visual analogue scale, but cisapride did so to a larger extent than placebo. The effects of cisapride partly outlasted active medication by at least four weeks. It is concluded that cisapride improves bowel habits in patients with idiopathic constipation and reduces laxative consumption.     

Symptom relief in gastroesophageal reflux disease: a randomized, controlled comparison of pantoprazole and nizatidine in a mixed patient population with erosive esophagitis or endoscopy-negative reflux disease.

OBJECTIVES: Gastroesophageal reflux disease (GERD) in primary care practice presents symptomatically, and resources to distinguish promptly between erosive esophagitis and endoscopy-negative reflux disease (ENRD) are limited. It is therefore important to determine the roles of proton pump inhibitors and histamine-2-receptor antagonists for first-line symptom-based therapy in patients with erosive esophagitis and ENRD. The aim of this study was to compare pantoprazole 40 mg once daily versus nizatidine 150 mg b.i.d. in a mixed GERD patient population with ENRD or erosive esophagitis (Savary-Miller grades 1-3). METHODS: A 4-wk randomized, double-blind, parallel-group, multicenter study conducted in Canada. Eligible patients had experienced GERD symptoms > or = 4 times weekly for > 6 months. Patients were randomized to pantoprazole 40 mg once daily or nizatidine 150 mg b.i.d.. Endoscopy was performed before randomization and after 4 wk of therapy. RESULTS: Of 220 patients randomized to therapy, 208 were available for a modified intent-to-treat analysis. Erosive esophagitis was present in 125 patients; 35 patients were Helicobacter pylori positive. There was complete symptom relief after 7 days of therapy in 14% of patients on nizatidine and in 40% of those on pantoprazole (p < 0.0001), and after 28 days of treatment in 36% and 63% of patients, respectively (p < 0.0001). After 28 days of treatment, adequate heartburn control was reported by 58% of the nizatidine group and in 88% of the pantoprazole (p < 0.0001); erosive esophagitis healing rates were 44% for nizatidine and 79% for pantoprazole (p < 0.001). Rescue antacid was needed by a greater number of patients using nizatidine than of those using pantoprazole (p < 0.001). H. pylori infection was associated with an increased probability of erosive esophagitis healing. CONCLUSIONS: Pantoprazole once daily was superior to nizatidine b.i.d. in producing complete heartburn relief in a mixed population of GERD patients and in achieving erosion healing. The proportions of patients with complete symptom relief were greater with pantoprazole after 7 days of therapy than with nizatidine after 28 days. The present study data suggest that pantoprazole is a highly effective first-line therapy for the management of gastroesophageal reflux disease in a primary care practice setting.     

Effects of cisapride on gastric emptying of oil and aqueous meal components, hunger, and fullness.

To evaluate the effects of cisapride on gastric emptying of extracellular fat and hunger and fullness 10 volunteers consumed a meal consisting of 60 ml technectium-99m (99mTc)-V-thiocyanate labelled olive oil and 290 ml indium-113m (113mIn) labelled soup after taking cisapride (10 mg four times daily orally) and placebo, each for four days, in randomised, double blind fashion. Gastric emptying was quantified scintigraphically. Hunger and fullness before and after the meal were evaluated using visual analogue scales. Cisapride accelerated gastric emptying of oil and aqueous components by reducing the lag phase mean (SEM) (20.3 (7.0) min v 40.7 (4.1) min (p < 0.05) for oil and 4.1 (2.5) min v 10.0 (3.1) min (p < 0.05) for aqueous). Cisapride had no effect on the post-lag emptying rate of oil. Treatment with cisapride was associated with reduced retention of oil in the proximal stomach (p < 0.05). Subjects were more hungry before ingestion of the meal while receiving cisapride (6.7 (0.9) v 3.9 (0.7), p < 0.001). The scores for hunger at 120 and 180 minutes were inversely related to gastric emptying of oil on both cisapride (r > -0.62, p < 0.05) and placebo (r > -0.86, p < 0.001). Fullness increased after the meal while receiving placebo (p < 0.01), but not cisapride and postprandial fullness was less with cisapride at (30 min; 0.4 (0.3) v 3.3 (1.0), p < 0.05). With placebo, but not cisapride, the score for fullness at 15 minutes was inversely related to emptying of the aqueous phase (r = 0.68, p < 0.05). These results show that in normal volunteers after ingestion of an oil/aqueous meal: (a) postprandial hunger is inversely related to gastric emptying of oil, while fullness is inversely related to gastric emptying of the aqueous phase, (b) cisapride affects the intragastric distribution and accelerates gastric emptying of both oil and aqueous meal components, and (c) cisapride increases preprandial hunger and reduces postprandial fullness.     

Ranitidine therapy for gastroesophageal reflux disease. Results of a large double-blind trial

In a multicenter, double-blind trial, 284 patients with gastroesophageal reflux disease were evaluated before, during, and after six weeks of treatment with either placebo or ranitidine (150 mg twice daily). Randomization resulted in two comparable patient groups. Ranitidine treatment was significantly more effective than placebo treatment in decreasing the frequency and the severity of heartburn during both daytime and nighttime assessment periods. There was a significant correlation between improvement in heartburn symptoms and decrease in antacid consumption; hence, patients receiving ranitidine consumed significantly fewer antacid tablets. Among patients with endoscopic esophagitis at baseline, the overall change in endoscopic classification after six weeks of therapy was significantly better for the ranitidine-treated patients. The ranitidine-treated group had less evidence of erosions and ulcerations as well as greater healing. There were no differences between the groups with respect to changes in esophageal mucosal sensitivity to acid perfusion or changes in histologic grading of esophageal mucosal biopsy specimens. The ranitidine safety profile was similar to that of previous studies. We conclude that, in patients with gastroesophageal reflux disease, ranitidine therapy, 150 mg twice daily, markedly reduced the heartburn symptoms of reflux disease and significantly improved the endoscopic appearance of the esophageal mucosa.     

Cisapride does not improve precolonoscopy bowel preparation with either sodium phosphate or polyethylene glycol electrolyte lavage

BACKGROUND: Oral sodium phosphate solution (NAP) and polyethylene glycol-electrolyte lavage (PEG-EL) are used for precolonoscopy bowel preparation. The benefit of adding cisapride to PEG-EL is controversial, and its influence on the effectiveness of NAP has not been investigated. The primary aim of this study was to determine whether cisapride improves the effectiveness and/or tolerableness of bowel preparation with either NAP or PEG-EL. METHODS: In 187 patients undergoing colonoscopy, a randomized, double-blind, placebo-controlled trial with a Latin square design was conducted to compare 4 different bowel preparations: NAP plus either cisapride (10 mg; 2 doses) or placebo, or PEG-EL plus either cisapride (10 mg; 1 dose) or placebo. Quality of the bowel preparation was graded by the endoscopist according to the amount of stool present in the colon (excellent, satisfactory, unsatisfactory). To assess tolerability, patients rated 8 symptoms, the taste of the lavage solution, and the ease of preparation on a 5-point scale (1: easy; 5: distressing). RESULTS: Endoscopists scored the bowel preparation as either excellent or satisfactory as follows: NAP: cisapride 50% versus placebo 61% (p = 0.3); PEG-EL: cisapride 80% versus placebo 78% (p = 1.0). Cisapride did not improve tolerability or the frequency of adverse symptoms associated with either solution. The ease of bowel preparation was significantly better in the NAP group versus PEG-EL group (mean score 1.8 versus 2.8; p < 0.0001). CONCLUSIONS: Cisapride does not improve the quality of bowel preparation with either NAP or PEG-EL. NAP is better tolerated by patients than PEG-EL; however, PEG-EL results in better bowel preparation.     

Rabeprazole for the prevention of pathologic and symptomatic relapse of erosive or ulcerative gastroesophageal reflux disease. Rebeprazole Study Group

OBJECTIVE: We evaluated the effectiveness and safety profile of 10 and 20 mg of rabeprazole, a new proton pump inhibitor, once daily versus placebo in preventing endoscopic and symptomatic relapse for up to 1 yr among patients with healed erosive or ulcerative gastroesophageal reflux disease (GERD). METHODS: The 52-wk trial used a multicenter, randomized, double-blind, parallel-group design in which 209 men and women were assigned to 10 or 20 mg of rabeprazole once daily in the morning or placebo. RESULTS: Both rabeprazole doses were significantly superior to placebo in preventing endoscopic relapse (p < 0.001), and 20 mg was significantly more effective than 10 mg (p < 0.04). Both doses were also significantly superior to placebo in reducing the frequency and severity of heartburn relapse (p < 0.001). When adjusted for differences in exposure to study medication, no significant differences were found in the incidence of adverse events. No clinically significant changes were found regarding clinical laboratory parameters, vital signs, electrocardiograms, ophthalmological evaluations, body weight, serum gastrin, and enterochromaffin-like cell histology. CONCLUSIONS: Once-daily therapy with 10 or 20 mg of rabeprazole effectively prevents pathological and symptomatic GERD relapse. The 20-mg dose is significantly more effective than the 10-mg dose in preventing endoscopic recurrence. Treatment was well tolerated, and no clinically significant safety findings emerged. Our findings support rabeprazole's efficacy in preventing GERD recurrence with excellent tolerability and a short-term favorable safety profile.     

Effect of chronic administration of cisapride on gastric emptying of a solid meal and on dyspeptic symptoms in patients with idiopathic gastroparesis.

In a double blind crossover comparison with placebo, the effects of cisapride (10 mg tid for two weeks), a non-antidopaminergic gastrointestinal prokinetic drug, on gastric emptying times and on symptoms were evaluated in 12 patients with chronic idiopathic dyspepsia and gastroparesis. Gastric emptying was studied by a radioisotopic gamma camera technique. The test meal was labelled in the solid component (99mTc-sulphur colloid infiltrated chicken liver). Nine symptoms (nausea, belching, regurgitations, vomiting, postprandial drowsiness, early satiety, epigastric pain or burning, heartburn) were graded weekly on a questionnaire. Cisapride was significantly more effective than placebo in shortening the t1/2 of gastric emptying (p2 = 0.04), but no significant difference was observed between the two treatments with regard to the improvement of total symptom score (p2 = 0.09). No side effects were reported during the study.     

Healing of grade-II and III oesophagitis through motility stimulation with cisapride

The clinical relevance of cispride's stimulating effects on lower oesophageal motility was studied in 19 patients with documented (endoscopy, biopsy) grade II or III oesophagitis. Patients were treated for 8 or 16 weeks (depending essentially on whether the result was cure or failure) with 10 mg of cisapride four times a day (n = 11) or placebo (n = 8). Cisapride was superior to placebo with regard to mucosal healing (p less than 0.001) and symptomatic improvement (p less than 0.05): at the end of treatment, healing (grade 0) was observed in 8 cisapride patients, against 1 placebo patient, and reflux symptoms had disappeared in 7 and 1 patients, respectively. In conclusion, cisapride was of significant benefit to oesophagitis patients and was well tolerated.     

Two doses of omeprazole versus placebo in symptomatic erosive esophagitis: the U.S. Multicenter Study.

Two hundred thirty patients with reflux symptoms and endoscopically proven erosive esophagitis were enrolled from 15 U.S. centers into a randomized, double-blind, dose-ranging study comparing placebo with omeprazole, 20 or 40 mg given once daily in the morning. Esophagitis grade 2 was present in 44% of patients, grade 3 in 37% of patients, and grade 4 in 19% of patients. Endpoints, defined as complete relief of heartburn and complete esophageal mucosal healing, were assessed after 4 and 8 weeks of treatment. Both omeprazole doses were significantly superior to placebo in complete endoscopic healing. After 8 weeks of treatment, 73.5% of patients in the 20-mg omeprazole group and 74.7% in the 40-mg omeprazole group, compared with 14.0% in the placebo group, had complete healing of the esophageal mucosa. At the end of the study, complete relief of daytime heartburn was obtained in 79.5% of patients in the 20-mg omeprazole group, 81.6% in the 40-mg omeprazole group, and 37.2% in the placebo group (P less than or equal to 0.05). Complete relief of nighttime heartburn was noted by 79.5% of patients in the 20-mg omeprazole group, 85.1% in the 40-mg omeprazole group, and 34.9% in the placebo group (P less than or equal to 0.05). The median time to complete relief of daytime and nighttime heartburn occurred earlier in the 40-mg group than in the 20-mg group (9 vs. 17 days and 9 vs. 20 days, respectively); however, these differences were not statistically significant. Relief of acid regurgitation and dysphagia also occurred earlier in the 40-mg group. Omeprazole was well tolerated in this group of patients. No unexpected adverse experiences occurred. The results of this study confirm those of six multicenter, international trials in which omeprazole in doses of 20-60 mg provided a degree of esophageal mucosal healing and complete relief of reflux symptoms superior to any other medical treatment.     

Management of heartburn in a large, randomized, community-based study: comparison of four therapeutic strategies

OBJECTIVE: Our objective was to compare four management strategies for heartburn: therapy with an H2-receptor antagonist (ranitidine), therapy with a proton pump inhibitor (lansoprazole), crossover from ranitidine to lansoprazole ("step-up" therapy), and crossover from lansoprazole to ranitidine ("step-down" therapy). METHODS: This was a controlled, double-blind, multicenter trial comprising 593 adults with heartburn, randomized to one of four groups for 20 wk. Subjects received either ranitidine 150 mg b.i.d. for 20 wk, or lansoprazole 30 mg once daily for 20 wk, or ranitidine 150 mg b.i.d. for 8 wk [corrected] followed by lansoprazole 30 mg once daily for 12 wk ("step-up"), or lansoprazole 30 mg once daily for 8 wk followed by ranitidine 150 mg b.i.d. for 12 wk ("step-down"). Outcome measures were based on self-reports in daily diaries of 24-h heartburn severity, measured by maximum daytime and nighttime severity, and percentage of 24-h heartburn-free days measured by absence of both daytime and nighttime heartburn. RESULTS: Median heartburn severity was significantly lower (p < 0.05) for lansoprazole (0.25) than the other groups (0.46 ranitidine, 0.44 "step-up," 0.35 "step-down"). The lansoprazole group had a significantly higher percentage of 24-h heartburn-free days (median 81.4%, p < 0.01) than other groups (66.6, 66.9, and 73.6%, respectively). In the "step-up" and "step-down" groups, heartburn was less severe, and percentages of 24-h heartburn-free days were higher during lansoprazole treatment regardless of treatment sequence. CONCLUSION: Proton pump inhibitor treatment provides more consistent heartburn relief than an H2-receptor antagonist, or "step-up" or "step-down" therapy.     

A randomized trial comparing omeprazole, ranitidine, cisapride, or placebo in helicobacter pylori negative, primary care patients with dyspepsia: the CADET-HN Study

BACKGROUND: The management of Helicobacter pylori negative patients with dyspepsia in primary care has not been studied in placebo-controlled studies. METHODS: H. pylori negative patients with dyspepsia symptoms of at least moderate severity (> or =4 on a seven-point Likert scale) were recruited from 35 centers. Patients were randomized to a 4-wk treatment of omeprazole 20 mg od, ranitidine 150 mg bid, cisapride 20 mg bid, or placebo, followed by on-demand therapy for an additional 5 months. Treatment success was defined as no or minimal symptoms (score < or = 2 out of 7), and was assessed after 4 wk and at 6 months. RESULTS: Five hundred and twelve patients were randomized and included in the intention-to-treat (ITT) analysis. At 4 wk, success rates (95% CI) were: omeprazole 51% (69/135; 43-60%), ranitidine 36% (50/139, 28-44%), cisapride 31% (32/105, 22-39%), and placebo 23% (31/133, 16-31%). Omeprazole was significantly better than all other treatments (p < 0.05). The proportion of patients who were responders at 4 wk and at 6 months was significantly greater for those receiving omeprazole 31% (42/135, 23-39%) compared with cisapride 13% (14/105, 7-20%), and placebo 14% (18/133, 8-20%) (p= 0.001), but not ranitidine 21% (29/139, 14-27%) (p= 0.053). The mean number of on-demand study tablets consumed and rescue antacid used was comparable across groups. Economic analysis showed a trade-off between superior efficacy and increased cost between omeprazole and ranitidine. CONCLUSION: Treatment with omeprazole provides superior symptom relief compared to ranitidine, cisapride, and placebo in the treatment of H. pylori negative primary care dyspepsia patients.