Famotidine relieves symptoms of gastroesophageal reflux disease and heals erosions and ulcerations. Results of a multicenter, placebo-controlled, dose-ranging study. USA Merck Gastroesophageal Reflux Disease Study Group.

We conducted a double-blind, placebo-controlled, multicenter trial comparing the efficacy of famotidine 40 mg administered at bedtime (HS), 20 mg given twice daily (BID), and placebo to relieve heartburn and to heal endoscopically documented esophageal erosions or ulcerations. A total of 338 patients were randomized: 135 to receive famotidine 40 mg HS, 137 to receive famotidine 20 mg BID, and 66 to receive placebo. In the group given famotidine 20 mg BID, there was a significantly greater proportion of patients with complete relief of daytime heartburn, and both famotidine groups demonstrated statistically significant advantages over placebo in global scores or by successful outcome. Antacid consumption was significantly reduced in the group given famotidine 20 mg BID as compared with placebo. Both famotidine regimens resulted in a significantly greater proportion of patients with complete endoscopic healing than placebo, with the BID dosing being numerically superior to the 40-mg HS dose.     

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.     

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.     

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.     

Sucralfate used as adjunctive therapy in patients with severe erosive peptic esophagitis resulting from gastroesophageal reflux

A total of 36 patients with grade 2 or greater erosive esophagitis and an abnormal 24-h pH monitor study, were treated in a randomized, double-blind fashion to assess the efficacy of sucralfate suspension as adjunctive therapy to cimetidine for severe esophagitis secondary to gastroesophageal reflux. Treatment consisted of cimetidine, 300 mg qid and either sucralfate suspension (1 g/10 ml) or an identical placebo suspension, 10 ml after meals and 20 ml hs. Patients were treated for 12 wk unless endoscopic healing occurred earlier. Initial evaluation and monthly follow-up consisted of symptom monitoring, endoscopic evaluation and pre- and post-therapy esophageal manometry, Bernstein test, and 24-h pH monitoring. The combination of cimetidine and sucralfate suspension was superior to cimetidine alone in improving daytime heartburn symptoms (p less than 0.05) but not nighttime heartburn, dysphagia, or regurgitation. Sucralfate plus cimetidine improved the overall endoscopic outcome of esophagitis more than cimetidine alone (p less than 0.05). More patients exhibited endoscopic healing in the adjunctive sucralfate group than in the cimetidine-only group. Endoscopic healing, however, was not statistically different between groups. We conclude that sucralfate used as adjunctive therapy to cimetidine resulted in improvement of some of the symptoms of reflux, and probably increases the likelihood of complete healing of esophagitis, compared with cimetidine alone.     

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.     

Efficacy and safety of omeprazole in Japanese patients with nonerosive reflux disease

BACKGROUND: There is increasing awareness of nonerosive reflux disease (NERD) as a disease requiring treatment in Japan. This randomized, double-blind, placebo-controlled, parallel-group study was conducted to investigate the efficacy and safety of omeprazole 10 mg and 20 mg once daily in Japanese patients with NERD. METHODS: Patients with heartburn for at least 2 days a week during the month before entry into the study and no endoscopic signs of a mucosal break (grade M or N according to Hoshihara's modification of the Los Angeles classification) were randomly assigned to one of three groups (omeprazole 10 mg or 20 mg, or placebo) once daily for 4 weeks. RESULTS: Overall, 355 patients were enrolled, of whom 284 were randomly assigned to one of the three groups (omeprazole 10 mg, n = 96; omeprazole 20 mg, n = 93; placebo, n = 95). The rate of complete resolution of heartburn in week 4 was significantly higher in patients treated with omeprazole 10 mg [32.3%, 95% confidence interval (CI), 22.9%-41.6%] or 20 mg (25.8%, 95% CI, 16.9%-34.7%) than in the placebo group (12.0%, 95% CI, 5.3%-18.6%). No significant difference between the two omeprazole groups was observed. The rate of complete resolution of heartburn by omeprazole was similar between patients with grade M and those with grade N esophagus. Omeprazole also increased the rate of sufficient relief from heartburn. Omeprazole was well tolerated. CONCLUSIONS: Omeprazole 10 mg or 20 mg once daily is effective and well tolerated in patients with NERD regardless of their endoscopic classification.     

A randomized,double-blind,placebo-controlled clinical study of the histamine H<Subscript>2</Subscript>-receptor antagonist famotidine in Japanese patients with nonerosive reflux disease

BACKGROUND: To investigate whether histamine H2-receptor antagonists are sufficient to treat heartburn in nonerosive reflux disease in Japanese, who produce less gastric acid than Westerners, the efficacy of famotidine in Japanese nonerosive reflux disease patients was studied in a double-blind, placebo-controlled, parallel group-comparative, multicenter study. METHODS: The Los Angeles classification system with Japanese modifications was used to assess the severity of nonerosive reflux disease. Famotidine (10-or 20-mg doses) or placebo was administered to patients twice daily for 8 weeks. Heartburn symptoms were recorded daily by patients. RESULTS: A total of 528 patients participated in the study. The percentage of days without heartburn, the primary end point of the efficacy evaluation, was 62% for 40 mg and 59% for 20 mg of famotidine, and 55% for placebo, with a statistically significant difference between the 40-mg dose and placebo (P = 0.001; significance level, 0.025 one-sided). Famotidine at both doses provided immediate relief from heartburn, and relief persisted throughout the 8-week study with the 40-mg dose. CONCLUSIONS: The results indicate that famotidine relieves heartburn symptoms in Japanese nonerosive reflux disease patients.     

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.     

Oral pantoprazole for erosive esophagitis: a placebo-controlled, randomized clinical trial. Pantoprazole US GERD Study Group

OBJECTIVES: The aim of this dose-response study was to compare the effectiveness of 10 mg, 20 mg, and 40 mg of pantoprazole with that of placebo tablets in the healing and symptom relief of gastroesophageal reflux disease associated with erosive esophagitis, and to determine the optimal dose. METHODS: A total of 603 patients with endoscopically confirmed (Hetzel-Dent scale) erosive esophagitis of grade 2 (64.5%) or grades 3 or 4 (35.3%) were enrolled in a double-blind, multicenter study and randomly assigned to receive pantoprazole (10 mg, 20 mg, or 40 mg) or placebo, administered once daily in the morning, for 4 or 8 wk depending on healing. RESULTS: The healing rates after 4 wk for placebo and pantoprazole 10 mg, 20 mg, and 40 mg/day were 14%, 42%, 55%, and 72%, respectively (p < 0.001 for all doses of pantoprazole vs placebo). Cumulative healing rates after 8 wk for placebo and pantoprazole 10 mg, 20 mg, and 40 mg/day were 33%, 59%, 78%, and 88%, respectively (p < 0.001 for all doses of pantoprazole vs placebo). The 40-mg pantoprazole dose produced greater rates of healing and earlier healing of esophagitis than either the 10- or 20-mg dose, regardless of severity. Pantoprazole, at any dose, was significantly more effective than placebo in relieving reflux symptoms. Patients on pantoprazole 40 mg experienced relief of symptoms on day 1 of treatment. No serious treatment-related adverse events occurred. CONCLUSIONS: Pantoprazole was safe and effective for healing erosive esophagitis and provided rapid symptomatic relief. These results indicate that pantoprazole offers a new option for treatment of erosive esophagitis. Among the three doses studied, the 40-mg dose was the most effective.     

Healing and relapse of severe peptic esophagitis after treatment with omeprazole

We have studied the response of erosive or ulcerative esophagitis to treatment with omeprazole and its subsequent relapse on cessation of therapy in 196 patients. In the first phase of the study omeprazole (20 or 40 mg daily) was compared with placebo in 64 patients. After 4 wk there was endoscopic healing in 81% (25 of 31) of omeprazole-treated patients and in only 6% (2 of 32) of placebo-treated patients. Endoscopic healing of esophagitis was accompanied by symptom relief and histologic healing of ulceration. In the second (dose finding) phase a further 132 patients were randomized to omeprazole (20 or 40 mg daily) and endoscopic healing was assessed. In patients with the mildest grade of ulcerative esophagitis (grade 2), healing occurred at 4 wk in 87% receiving 20 mg and in 97% receiving 40 mg. In patients with grade 3 esophagitis, 67% (20 mg) and 88% (40 mg) were healed. Less than half the patients with grade 4 esophagitis (Barrett's ulcers or confluent ulceration) healed with either 20 mg (48%) or 40 mg (44%). Regression analysis in the 164 omeprazole-treated patients showed no evidence that healing was influenced by factors other than severity of esophagitis at entry and omeprazole dose. In phase 3 of the study the rate of endoscopic relapse was determined in 107 endoscopically healed patients after stopping omeprazole. Erosive or ulcerative esophagitis recurred in 88 of 107 (82%) by 6 mo. Neither initial dose, grade of esophagitis, nor smoking was shown to influence relapse rate. Omeprazole is a highly effective treatment for peptic esophagitis. The 40-mg/day dosage produces endoscopic healing slightly more quickly than the 20-mg/day dosage, and the initial endoscopic gradings are of prognostic value. Relapse occurs rapidly when treatment is stopped.     

Comparing lansoprazole and omeprazole in onset of heartburn relief: results of a randomized, controlled trial in erosive esophagitis patients

OBJECTIVE: This randomized, double-blind, multicenter study was conducted to confirm a previous finding that lansoprazole relieves heartburn faster than omeprazole in patients with erosive esophagitis. METHODS: A total of 3510 patients with erosive esophagitis and at least one episode of moderate to very severe daytime and/or nighttime heartburn during the 3 days immediately before the screening visit were randomized to lansoprazole 30 mg once daily or omeprazole 20 mg once daily for 8 wk. Patients recorded the presence and severity of daytime and nighttime heartburn in daily diaries. On treatment days 1-4, patients were telephoned to confirm the completion of their daily diary. The primary efficacy parameters were the percentage of heartburn-free days and heartburn-free nights, as well as the average severity of daytime and nighttime heartburn. RESULTS: During treatment day I and all evaluation time points including the entire 8-wk treatment period, significantly (p < 0.05) higher percentages of patients treated with lansoprazole than those treated with omeprazole did not experience a single episode of heartburn. Onset of heartburn relief was more rapid in lansoprazole-treated versus omeprazole-treated patients: on day 1, 33% versus 25% of lansoprazole- versus omeprazole-treated patients were heartburn-free. The percentages of heartburn-free days and heartburn-free nights were also significantly (p < 0.01) greater for patients treated with lansoprazole at all evaluation time points. Heartburn severity was significantly less among those treated with lansoprazole compared with omeprazole. Both treatments were safe and well tolerated. CONCLUSIONS: Over 8 wk, lansoprazole 30 mg once daily relieved heartburn symptoms faster and more effectively than omeprazole 20 mg once daily in patients with erosive esophagitis.     

Cisapride 20 mg b.i.d. Provides Symptomatic Relief of Heartburn and Related Symptoms of Chronic Mild to Moderate Gastroesophageal Reflux Disease

Objective: We evaluated the efficacy and safety of a twice-daily dosage regimen of cisapride 20 mg in relieving the symptoms of mild-moderate gastroesophageal reflux disease (GERD) in patients with moderate intensity heartburn and no history of erosive esophagitis.
Methods: After a 2-wk, single-blind, placebo run-in period, 398 patients who continued to experience moderate intensity heartburn were randomized to either placebo (  n = 196  ) or cisapride 20 mg (  n = 202  ) twice daily for 4 wk.
Results: Compared with placebo, cisapride significantly reduced scores for daytime and nighttime heartburn (   p < 0.001  ), total regurgitation (   p < 0.001  ), eructation (   p = 0.04  ), and early satiety (   p = 0.04  ). Cisapride 20 mg b.i.d. was also superior to placebo in reducing total use of rescue antacid medication (   p < 0.001  ); reducing, in concordance analyses, daytime and nighttime heartburn with antacid usage (   p < 0.001  ); increasing the percentage of heartburn-free days and antacid-free nights (   p < 0.5  ); and increasing the percentage of patients self-rated as having minimal or better symptomatic improvement (   p = 0.01  ). Cisapride 20 mg b.i.d. was well tolerated. The most common adverse event in the cisapride group was diarrhea, reported by 10% of patients, compared with an incidence of 4% in the placebo group.
Conclusion: Cisapride 20 mg b.i.d. was shown to be effective and safe for the short-term treatment of daytime and nighttime heartburn and for other symptoms associated with mild-moderate GERD.     

Effect of omeprazole and sucralfate on prepyloric gastric ulcer. A double blind comparative trial and one year follow up.

This study compared healing rates, relief of symptoms, frequency of adverse events, and proportion of patients in remission after one year follow up in 104 patients with active prepyloric ulcer during treatment with 40 mg omeprazole once daily or 2 g sucralfate twice daily, using a randomised double blind controlled trial. Healing rates after two, four, and six weeks were (omeprazole/sucralfate) 49%/23%; 83%/59%; 90%/70% respectively. After two weeks, omeprazole was more efficient than sucralfate in relief of daytime and nocturnal epigastric pain, nausea, and heartburn. The proportion of patients in remission after one year follow up was significantly higher in the omeprazole group (p < 0.01). Of the healed patients ulcers recurred in 36% in the omeprazole group and in 46% in the sucralfate group. It is concluded that the ulcer healing rate was higher and symptom relief was more pronounced in the omeprazole group compared with the sucralfate group, and that more patients were still in remission after a one year follow up period.     

Efficacy of adding sodium alginate to omeprazole in patients with nonerosive reflux disease: a randomized clinical trial

Nonerosive reflux disease (NERD) is the most common form of gastroesophageal reflux disease. Patients with NERD have a lower response rate to proton pump inhibitors (PPIs) than patients with erosive esophagitis when gauged from relief of heartburn. Sodium alginate decreases the acidity of refluxate and protects the esophageal mucosa. However, whether the addition of sodium alginate to PPI therapy can improve NERD symptoms remains unknown. Accordingly, the aim of this study was to evaluate the efficacy of adding sodium alginate to basal PPI therapy for NERD. Patients who had experienced heartburn on at least 2 days per week during the 1-month period before entering the study and had no endoscopic mucosal breaks (grade M or N according to Hoshihara's modification of the Los Angeles classification) were randomized to one of two treatments for 4 weeks: omeprazole (20 mg once daily) plus sodium alginate (30 mL four times a day) (group A) or omeprazole (20 mg once daily) alone (group B). Eighty-seven patients were enrolled, and 76 patients were randomly assigned to group A (n = 36) or group B (n = 40). Complete resolution of heartburn for at least 7 consecutive days by the end of treatment was significantly more common in group A (56.7%) than in group B (25.7%). One patient from group A had mild drug-related diarrhea that was not clinically serious. In conclusion, omeprazole combined with sodium alginate was better than omeprazole alone in Japanese patients with NERD.     

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 (40 mg) is superior to ranitidine in short-term treatment of ulcerative reflux esophagitis

The efficacy and safety of omeprazole, 40 mg once daily for four to eight weeks of treatment, were studied in 61 patients with ulcerative reflux esophagitis. A double-blind controlled study design was used, and the patients were randomly allocated to treatment with either omeprazole 40 mg once daily or ranitidine 150 mg twice daily. Endoscopy was performed prior to inclusion into the study, after four weeks and, if unhealed, again after eight weeks. Healing of esophagitis was defined as complete disappearance of all esophageal ulcerations. Symptoms were recorded before entry, after four weeks, and again after eight weeks in unhealed patients. Fifty-one patients were included in the per-protocol analysis at day 29, and 50 patients at day 57. The healing rate after four weeks of treatment was 22 of 26 patients (85%) treated with omeprazole and 10 of 25 patients (40%) treated with ranitidine (P<0.001). The corresponding figures after eight weeks were 24 of 25 (96%), and 13 of 25 (52%) (P<0.001). These results were confirmed in the intent-to-treat analysis. Patients treated with omeprazole showed a significantly faster and more profound relief in heartburn than patients treated with ranitidine: 85% had no heartburn after four weeks of treatment with omeprazole compared to 24% in patients treated with ranitidine (P=0.00007). The percentage of patients who were free of all reflux symptoms was significantly greater in the omeprazole-treated group as compared to the ranitidine-treated group (62% and 12% respectively, P=0.0001). There were no clinically significant changes in laboratory values in any of the treatment groups. Adverse events were few and mainly mild and transient.     

Early heartburn relief with proton pump inhibitors: a systematic review and meta-analysis of clinical trials.

BACKGROUND & AIMS: Proton pump inhibitors (PPIs) are often taken for short-term treatment of heartburn. We performed a systematic review of the efficacy of PPIs for heartburn relief within the first 1-2 days of therapy. METHODS: Bibliographic databases were searched for clinical trials of PPIs in patients with heartburn that provided information about the proportion with heartburn relief at day 1-2. The sample size-weighted pooled proportions of patients with complete or sustained (7 consecutive days) relief were calculated. Meta-analyses of randomized comparisons of PPIs were also performed. RESULTS: Eighteen trials met inclusion criteria. At day 1 of PPI therapy, complete 24-hour, daytime, nighttime, and sustained heartburn relief occurred in 0.31 (95% confidence interval [CI], 0.30-0.32), 0.49 (95% CI, 0.48-0.50), 0.55 (95% CI, 0.53-0.56), and 0.21 (95% CI, 0.20-0.22) of patients. Up to 37% of the heartburn relief achievable with 28 days of PPIs occurred on day 1. Placebo was significantly less effective than PPIs for 24-hour relief on day 1 (relative risk [RR], 0.41; 95% CI, 0.29-0.58), and single-dose PPI therapy was less effective than double-dose therapy (RR, 0.82; 95% CI, 0.74-0.92). CONCLUSIONS: Complete heartburn relief for the entire day occurs in approximately 30% of patients after their first PPI dose and 9% of patients after their first placebo (RR for relief on day 1 for placebo versus PPI was 0.41 [95% CI, 0.28-0.58]). Although PPIs might provide benefit from the first day of therapy, most patients will not have symptom relief with 1 or 2 days of PPI therapy.     

Symptom relief in patients with reflux esophagitis: comparative study of omeprazole, lansoprazole, and rabeprazole

BACKGROUND AND AIM: Rabeprazole has a faster onset of antisecretory activity than omeprazole and lansoprazole. The aim of the present study was to clarify whether there is any difference in the speed of symptom relief in patients with reflux esophagitis following the administration of these three proton pump inhibitors (PPI). METHODS: Eighty-five patients with erosive reflux esophagitis were randomized to receive 8 weeks of 20 mg of omeprazole (n = 30), 30 mg of lansoprazole (n = 25), or 20 mg of rabeprazole (n = 30) once a morning. Daily changes in heartburn and acid reflux symptoms in the first 7 days of administration were assessed using a six-point scale (0: none, 1: mild, 2: mild-moderate, 3: moderate, 4: moderate-severe, 5: severe). RESULTS: The mean heartburn score in patients administered rabeprazole decreased more rapidly than those given the other PPI. Complete heartburn remission also occurred more rapidly in patients administered rabeprazole (compared with omeprazole: P = 0.035, compared with lansoprazole: P = 0.038 by log-rank test). No differences were seen in the rate of endoscopic healing of reflux esophagitis at 8 weeks between the three treatment regimens. CONCLUSION: Rabeprazole may be more effective than omeprazole and lansoprazole for the rapid relief of heartburn symptoms in patients with reflux esophagitis.