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

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

Gastric acid control with esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole: a five-way crossover study

OBJECTIVES: Proton pump inhibitors owe their clinical efficacy to their ability to suppress gastric acid production. The objective of this study was to evaluate and compare intragastric pH following standard doses of esomeprazole, lansoprazole, omeprazole, pantoprazole and rabeprazole. METHODS: This randomized, open-label, comparative five-way crossover study evaluated the 24-h intragastric pH profile of oral esomeprazole 40 mg, lansoprazole 30 mg, omeprazole 20 mg, pantoprazole 40 mg, and rabeprazole 20 mg once daily in 34 Helicobacter pylori-negative patients aged 18-60 yr with symptoms of gastroesophageal reflux disease. Patients were randomly assigned to one of five treatment sequences and study drug was taken on 5 consecutive mornings 30 minutes prior to a standardized breakfast. A washout period of at least 10 days separated each treatment phase. RESULTS: Thirty-four patients provided evaluable data for all five comparators. The mean number of hours of evaluable pH data was > or =23.75 hours. On day 5, intragastric pH was maintained above 4.0 for a mean of 14.0 h with esomeprazole, 12.1 h with rabeprazole, 11.8 h with omeprazole, 11.5 h with lansoprazole, and 10.1 h with pantoprazole (p < or = 0.001 for differences between esomeprazole and all other comparators). Esomeprazole also provided a significantly higher percentage of patients with an intragastric pH greater than 4.0 for more than 12 h relative to the other proton pump inhibitors (p < 0.05). The frequency of adverse events was similar between treatment groups. CONCLUSIONS: Esomeprazole at the standard dose of 40 mg once daily provided more effective control of gastric acid at steady state than standard doses of lansoprazole, omeprazole, pantoprazole, and rabeprazole in patients with symptoms of gastroesophageal reflux disease.     

Comparison of pantoprazole 20 mg to ranitidine 150 mg b.i.d. in the treatment of mild gastroesophageal reflux disease

BACKGROUND: Despite a high prevalence of mild gastroesophageal reflux disease (GERD), few studies investigated efficacy and safety of proton pump inhibitors in this indication. This randomized double-blind study compares pantoprazole to ranitidine in GERD 0 and I, i.e. reflux without esophagitis or with confined lesions only. METHODS: Patients received either pantoprazole 20 mg o.a.d. or ranitidine 150 mg b.i.d. Outcome was assessed after 2 and 4 weeks. Primary criterion was relief of leading symptoms, i.e. heartburn, acid eructation and pain on swallowing, after 4 weeks of treatment. RESULTS: According to the per-protocol (PP) analysis, 69% (100/144) and 80% (115/144) of patients in the pantoprazole group were relieved of leading symptoms after 2 and 4 weeks, respectively. The rates in the ranitidine group were 47% (62/133) and 65% (86/133). Thus, superiority of pantoprazole could be proven. Quality-of-life parameters improved more in the pantoprazole group and patients' assessment of treatment was more favorable. Analysis for Helicobacter pylori status showed infection to lead to higher symptom relief rates. Both study medications were well tolerated. CONCLUSION: Pantoprazole 20 mg demonstrated superior efficacy with faster relief of reflux symptoms and similar tolerability compared to ranitidine 150 mg in the treatment of mild GERD.     

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.     

Effect of esomeprazole 40 mg vs omeprazole 40 mg on 24-hour intragastric pH in patients with symptoms of gastroesophageal reflux disease

Maintenance of intragastric pH > 4 is vital for effective management of gastroesophageal reflux disease (GERD). Esomeprazole 40 mg, the first proton pump inhibitor developed as an optical isomer, demonstrates improved acid inhibition over omeprazole 20 mg. Our aim was to compare esomeprazole 40 mg with omeprazole 40 mg, once-daily, on intragastric acidity in patients with symptoms of GERD. In this open-label, crossover study, 130 patients with symptoms of GERD received esomeprazole 40 mg or omeprazole 40 mg once-daily for five days. The 24-hr intragastric pH was monitored on days 1 and 5 of each treatment period. The mean percentage of the 24-hr period with intragastric pH > 4 was significantly greater (P < 0.001) with esomeprazole 40 mg than with omeprazole 40 mg on days 1 (48.6% vs 40.6%) and 5 (68.4% vs 62.0%). Interpatient variability was significantly less with esomeprazole than omeprazole. Esomeprazole was well tolerated. In conclusion, esomeprazole 40 mg provides more effective acid control than twice the standard dose of omeprazole.     

Symptom-relieving effect of esomeprazole 40 mg daily in patients with heartburn

BACKGROUND: To assess symptom relief in patients with heartburn following treatment with esomeprazole 40 mg daily. METHODS: Patients with heartburn (for > or = 6 months) were assessed in this double-blind, multicenter study. After a 3-day single-blind placebo run-in, 440 patients were randomized to esomeprazole 40 mg o.d., esomeprazole 20 mg b.i.d. or placebo for 14 days. Heartburn symptoms were recorded daily; as insufficient patients had data available from days 13 and 14, analyses included data up to day 12. Gastroesophageal reflux disease (GERD) was diagnosed by upper GI endoscopy and 24-h pH-monitoring. The primary end-point was total heartburn relief defined as no heartburn symptoms during the preceding 24-h period. RESULTS: 240 patients had erosive esophagitis (EO) and 114 patients had GERD defined by pH-monitoring. Proportions of patients with total heartburn relief increased during the first days of treatment and stabilized after Day 4. Total heartburn relief occurred in 67%-73%, 62%-70%, and 21%-32% of patients in the esomeprazole 40 mg o.d., esomeprazole 20 mg b.i.d., and placebo groups, respectively, between days 6 and 12. Proportions of patients with total heartburn relief were higher in patients with EO (71%-80% of patients from Day 4 onwards) compared to those without EO (52%-67% of patients from Day 4 onwards). Figures for patients diagnosed by pH-monitoring were 65%-73% of those with a positive diagnosis and 51%-58% with a negative diagnosis. CONCLUSION: Esomeprazole 40 mg o.d. treatment produces total heartburn relief in a high proportion of patients with GERD. Once-daily esomeprazole 40 mg dosing is recommended as no advantage was gained by splitting the dose.     

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.     

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.     

Comparative study of omeprazole, lansoprazole, pantoprazole and esomeprazole for symptom relief in patients with reflux esophagitis

AIM： To clarify whether there is any difference in the symptom relief in patients with reflux esophagitis following the administration of four Proton pump inhibitors （PPIs）. METHODS： Two hundred and seventy-four patients with erosive reflux esophagitis were randomized to receive 8 wk of 20 mg omeprazole （n = 68）, 30 mg of lansoprazole （n = 69）, 40 mg of pantoprazole （n = 69）, 40 mg of esomeprazole （n = 68） once a day in the morning. Daily changes in heartburn and acid reflux symptoms in the first 7 d 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 treated with esomeprazole more rapidly decreased than those receiving other PPI. Complete resolution of heartburn was also more rapid in patients treated with esomeprazole for 5 d compared with omeprazole （P = 0.0018, P = 0.0098, P = 0.0027, P = 0.0137, P = 0.0069, respectively）, lansoprazole （P = 0.0020, P = 0.0046, P = 0.0037, P = 0.0016, P = 0.0076, respectively）, and pantoprazole （P = 0.0006, P = 0.0005, P = 0.0009, P = 0.0031, P = 0.0119, respectively）. There were no significant differences between the four groups in the rate of endoscopic healing of reflux esophagitis at week 8. CONCLUSION： Esomeprazole may be more effective than omeprazole, lansoprazole, and pantoprazole for the rapid relief of heartburn symptoms and acid reflux symptoms in patients with reflux esophagitis.     

No clinical benefit of adding cisapride to pantoprazole for treatment of gastro-oesophageal reflux disease

OBJECTIVE: Although a proton pump inhibitor (PPI) and a prokinetic drug are often combined for the medical treatment of gastro-oesophageal reflux disease (GORD), there are few well-conducted clinical studies on the efficacy and tolerability of this therapy. This study investigates whether pantoprazole plus cisapride leads to an additional benefit in comparison to pantoprazole alone. DESIGN AND SETTING: Randomized double-blind prospective multicentre study conducted in patients of 33 hospitals in Ireland, South Africa and the UK. PARTICIPANTS: A total of 350 intention-to-treat (ITT) patients aged 18 years or older with GORD of grade II and III were included in the study. The per-protocol (PP) population comprised 152 patients in the pantoprazole group and 136 in the pantoprazole plus cisapride group. INTERVENTIONS: Patients received either pantoprazole 40 mg once daily or pantoprazole 40 mg once daily plus cisapride 20 mg twice daily. Treatment outcome was assessed after 4 and 8 weeks. The primary criterion was endoscopically confirmed healing after 4 weeks. Additionally, relief of leading symptoms was studied. MAIN OUTCOME MEASURES: The prior null hypothesis was no difference in healing rates between both treatment groups. RESULTS: After 4 weeks of treatment 81% and 82%, and after 8 weeks 89% and 90%, of PP patients treated with pantoprazole or pantoprazole plus cisapride were healed, respectively. Thus, equivalence of the two treatment strategies could be proven. Additionally, improvement of symptom relief showed no significant difference between the two regimens. In contrast to disease grade at baseline, Helicobacter pylori status did not influence the healing rates in our study. Both study medications were tolerated well. CONCLUSION: Addition of cisapride to pantoprazole provides no further benefit in the treatment of GORD.     

Effect of intravenous application of esomeprazole 40 mg versus pantoprazole 40 mg on 24-hour intragastric pH in healthy adults

BACKGROUND: It has been demonstrated that therapy with proton pump inhibitors reduces recurrence of bleeding following initial endoscopic treatment of bleeding peptic ulcers. AIM: This study compared the effects of esomeprazole 40 mg and pantoprazole 40 mg on intragastric acid control. Both substances were administered intravenously as 15-min infusion and as bolus injection. METHODS: Healthy men and women volunteers were enrolled in this single-center, open, randomized, three-way crossover study. After administration of esomeprazole 40 mg and pantoprazole 40 mg intravenously as 15-min infusion, and pantoprazole 40 mg intravenously as bolus injection, continuous 24-h intragastric pH monitoring was carried out. RESULTS: pH data were available for 21 Helicobacter pylori-negative and seven H. pylori-positive volunteers. In H. pylori-negative volunteers, esomeprazole 40 mg intravenously resulted in 11.8 h with an intragastric pH>4 compared with 5.6 h for pantoprazole 40 mg intravenously as infusion (P<0.0001), and 7.2 h for pantoprazole 40 mg intravenously as bolus injection (P<0.001). During the first 6 h of administration, the corresponding values were 3.4, 1.1 (P<0.000001), and 2.1 h (P<0.001), respectively. CONCLUSIONS: In H. pylori-negative patients, a single dose of esomeprazole 40 mg intravenously provides an intragastric acid control that is faster and more pronounced than administration of pantoprazole 40 mg intravenously.     

Night-time gastro-oesophageal reflux disease: prevalence, hazards, and management

Patients who complain of symptoms of gastro-oesophageal reflux disease (GORD) that occur at night require special attention. Night-time GORD can profoundly impair quality of life by causing pain, disturbing sleep, and interfering with next-day mental and physical functioning. Sleep impairs oesophageal acid clearance resulting in a prolongation of acid mucosal contact, and nocturnal reflux portends a greater risk of erosive oesophagitis and other significant complications of gastro-oesophageal reflux. Lifestyle changes such as elevating the head of the bed and adjusting the sleeping position can relieve night-time heartburn, and instituting some dietary changes along with occasional use of histamine H2 blockers can also be helpful. Relief of night-time reflux and its attendant symptoms usually requires a medication with acid-suppressing properties that extend into the sleeping interval. In most instances, more powerful acid suppression in the form of proton-pump inhibitors will be required. Clinical studies have shown that 40 mg esomeprazole provides better control of night-time GORD symptoms than 20 mg omeprazole or 30 mg lansoprazole. Furthermore, 40 mg pantoprazole offers even faster relief than 40 mg esomeprazole for night-time GORD symptoms. Of the several proton-pump inhibitors available on the market, esomeprazole and pantoprazole appear to have some advantages, which have been documented in recent studies. Esomeprazole has been shown to be more effective than lansoprazole in relieving GORD symptoms, and esomeprazole and pantoprazole appear to be equally effective in resolving GORD symptoms in a comparative study. Pantoprazole has pharmacokinetic properties that document a longer half-life compared with the other proton-pump inhibitors, and pantoprazole has the slowest inhibition recovery rate. These properties lend credence to pantoprazole as an effective treatment for associated symptoms of night-time reflux.     

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.     

High-dose esomeprazole is required for intraesophageal acid control in gastroesophageal reflux disease patients with hiatus hernia

Background and Aim: The aim of this study was to assess whether the efficacy of proton pump inhibitors (PPI) therapy at a standard dose in esophageal acid control is affected by the presence of hiatus hernia in Chinese gastroesophageal reflux disease patients, and whether a higher dose of PPI is required for acid control. Methods: Consecutive gastroesophageal reflux disease patients who had typical reflux symptoms and abnormal baseline 24‐h esophageal pH and underwent upper endoscopy were enrolled to receive esomeprazole at 40 mg once daily for 4 weeks. Patients underwent the dual‐channel 24‐h pH test at the end of 4‐week therapy. If the 24‐h esophageal pH was still abnormal at the end of 4‐week therapy, then esomeprazole at 40 mg twice daily was given for another 4 weeks after a washout interval of 1 week, and a 24‐h pH test was repeated at the end of the therapy. Results: Overall, 76 patients were included, 13 with hiatus hernia. Of the 76 patients treated with a 40 mg of esomeprazole daily, esophageal acid exposure was normalized in 64 (84.2%). Normalization of acid exposure was achieved by standard PPI therapy in 53.2% (7/13) of patients with hiatus hernia and 90.5% (57/63) of those without (P = 0.004). A double dose of esomeprazole was successful in normalizing the esophageal pH in all 12 non‐responders to the standard dose of esomeprazole, including the six patients with hiatus hernia and six patients without. Conclusions: The standard‐dose of esomeprazole fails to normalize the esophageal pH in almost 50% of patients with hiatus hernia, in whom the “double‐dose” esomeprazole therapy is required.     

Financial restrictions in health care systems could affect treatment quality of GERD-patients

AIMS: To directly compare the efficacy and safety of pantoprazole 40 mg VS. omeprazole 20 mg in patients with gastroesophageal reflux disease (GERD). MATERIAL AND METHODS: 915 Patients suffering from symptomatic GERD B-D (Los Angeles classification) were included in a double-blind randomized multicenter clinical trial and treated with either pantoprazole 40 mg od or omeprazole 20 mg od for six weeks. Primary efficacy criterion was the first time to reach normal symptoms as assessed by the questionnaire ReQuest-GI. RESULTS: Compared to omeprazole 20 mg, pantoprazole 40 mg achieved a significantly faster rate of symptom relief (p = 0.0298). Thus, as assessed with the ReQuest questionnaire, patients treated with pantoprazole 40 mg experienced relief from the 7 leading GERD symptoms 2 days earlier than those treated with omeprazole 20 mg. Long-lasting sustained relief from symptoms was also achieved earlier with pantoprazole than with omeprazole; in patients treated with pantoprazole, the daily symptom load was lower than in those treated with omeprazole. After 6 weeks of treatment, over 90 percent of patients were free from symptoms in both treatment groups (93.7 % in the pantoprazole, vs. 91.8 % in the omeprazole group, PP). Both medications were well tolerated. CONCLUSIONS: GERD patients treated with pantoprazole 40 mg experience a significantly faster relief from their leading symptoms than those treated with omeprazole 20 mg.     

Gastric Helicobacter pylori infection accelerates healing of reflux esophagitis during treatment with the proton pump inhibitor pantoprazole.

BACKGROUND & AIMS: In previous studies an exaggerated effect of proton pump inhibitors (PPIs) on intragastric pH in Helicobacter pylori-infected patients was observed. Because healing and improvement of symptoms in patients with gastroesophageal reflux disease (GERD) is directly associated with an increase of intragastric pH during treatment, we hypothesized that the response to treatment with a PPI in patients with reflux esophagitis would be better in H. pylori-infected patients than in patients without H. pylori infection. METHODS: We recruited 971 patients with endoscopically verified reflux esophagitis grades II and III (Savary/Miller). At study entry, H. pylori status was assessed by a 13C-urea breath test and baseline characteristics were recorded. Physicians and patients were not notified about the results of the breath test until completion of the study. All patients underwent treatment with pantoprazole, 40 mg orally once daily for 4 weeks. Healing was verified by endoscopy after 4 or 8 weeks of treatment. If the esophagitis had not completely healed at this time, treatment was continued for a further 4-week period. Healing rates and symptom relief were compared for patients with and without H. pylori infection. RESULTS: The prevalence of H. pylori was 39.9% (95% confidence interval [CI], 36.9-42.9), and neither gender, smoking, nor alcohol consumption were associated with the H. pylori infection (P > 0.4). The trial was completed by 846 patients without protocol violation. Overall healing rates of reflux esophagitis were 80.4% (95% CI, 77.7-83.1) and 93.6% (95% CI, 91.8-95.2) after 4 and 8 weeks, respectively. In H. pylori-positive patients, healing rates were significantly higher after 4 (86.6% vs. 76.3%; P = 0.0005) and 8 weeks (96.4% vs. 91.8%; P < 0.004). Relief of symptoms after 4 weeks was also significantly (P < 0.05) better in H. pylori-infected patients than in uninfected patients. CONCLUSIONS: Patients with reflux esophagitis and H. pylori infection respond significantly better than H. pylori-negative patients to the PPI pantoprazole.     

Efficacy and tolerability of 20 mg pantoprazole versus 300 mg ranitidine in patients with mild reflux-oesophagitis: a randomized, double-blind, parallel, and multicentre study

BACKGROUND AND AIM: The aim of this study was to compare the efficacy and tolerability of low dose pantoprazole (20 mg) (a gastric proton pump inhibitor) with standard dose ranitidine (300 mg) (a histamine-receptor antagonist), in their ability to relieve symptoms and heal oesophageal lesions associated with gastrooesophageal reflux disease (GORD). METHODS: Patients with endoscopically established mild GORD (stage I, modified Savary-Miller classification) were enrolled into a multicentre, randomized, double-blind, parallel-group comparison study (intention-to-treat population, n = 201; age range, 18-82 years). Patients took either oral pantoprazole 20 mg in the morning (n = 101) or ranitidine 300 mg in the evening (n = 100) once daily for 4 weeks or, if the healing was not complete, 8 weeks. Relief from key symptoms (heartburn, acid regurgitation, pain on swallowing) was assessed after 2, 4, and if applicable, 8 weeks. Healing of lesions was confirmed endoscopically after 4 and, if applicable, 8 weeks. RESULTS: Complete relief from key symptoms was noted after 2 weeks in 70/88 (80%) patients treated with pantoprazole vs 45/89 (51%) patients treated with ranitidine ('per-protocol and key-point available' populations, P < 0.001); the corresponding results after 4 weeks were 77/88 (88%) vs 51/88 (58%) (P < 0.001). Complete healing of lesions after 4 weeks of treatment was seen in 74/88 (84%) vs 49/89 (55%) in the pantoprazole and ranitidine group, respectively (P < 0.001, per-protocol); by week 8 the cumulative healing rates were 84/88 (95%) vs 69/89 (78%) in the pantoprazole and ranitidine group, respectively (P < 0.001). For the intention-to-treat populations, the corresponding values for healing after 4 and 8 weeks were 73% vs 49% (P < 0.001) and 83% vs 69% (P < 0.05), respectively. Both study medications were well tolerated. CONCLUSION: Compared to ranitidine 300 mg, the regimen with pantoprazole 20 mg provides faster relief from symptoms and is significantly more effective in healing of oesophageal lesions in patients with mild reflux-oesophagitis. Thus, the low dose of pantoprazole offers a treatment approach which minimizes drug exposure and costs while retaining high efficacy.     

Esomeprazole 40 mg and 20 mg is efficacious in the long-term management of patients with endoscopy-negative gastro-oesophageal reflux disease: a placebo-controlled trial of on-demand therapy for 6 months

BACKGROUND: On-demand therapy may offer an effective approach to the long-term management of gastro-oesophageal reflux disease (GORD) without oesophagitis. AIM: To examine the efficacy of the novel proton pump inhibitor esomeprazole as on-demand therapy in endoscopy-negative GORD. PATIENTS AND METHODS: Endoscopy-negative GORD patients who achieved complete resolution of heartburn after short-term esomeprazole or omeprazole treatment (n = 721) were randomized to esomeprazole 20 mg (n = 282), 40 mg (n = 293) or placebo (n = 146) on demand (maximum one dose/day) for 6 months. The primary and secondary efficacy endpoints were time to study discontinuation due to (i) unwillingness to continue and (ii) inadequate control of heartburn, respectively. RESULTS: Both doses of esomeprazole were more effective than placebo. During the 6-month period, 42% of placebo recipients discontinued treatment due to unwillingness to continue, compared with 8% and 11% of esomeprazole 20 mg and 40 mg recipients, respectively. Overall, more patients treated with esomeprazole were free from gastrointestinal symptoms after 6 months of on-demand therapy. CONCLUSIONS: Esomeprazole 20 mg was superior to placebo for on-demand treatment of GORD; a higher dose did not confer additional clinical benefit. Over 90% of patients were willing to continue on-demand treatment with esomeprazole 20 mg over a 6-month period.     

Esomeprazole 40 mg once a day in patients with functional dyspepsia: the randomized, placebo-controlled "ENTER" trial

OBJECTIVE: The etiologies of functional dyspepsia (FD) are unclear, but in some studies, treatment with a proton pump inhibitor has been beneficial. The objective of this study was to evaluate the efficacy of esomeprazole 40 mg once a day compared to placebo in achieving symptom relief in primary care patients with FD. METHODS: This was a randomized, placebo-controlled trial in adult FD patients, who had at least moderate severity of symptoms, defined as a score of > or =4 on a 7-point Global Overall Symptom (GOS) scale. Patients were excluded if they had predominant symptoms of heartburn or regurgitation; after a normal baseline endoscopy, patients were randomized to esomeprazole 40 mg once daily or placebo for 8 wk. The primary outcome measure was symptom relief (GOS < or =2) at 8 wk. RESULTS: Of the 502 enrolled patients, 224 were randomized. The main reasons for exclusion were abnormal endoscopic findings, especially esophagitis. A significantly greater proportion of patients in the esomeprazole group achieved symptom relief at 4 but not at 8 wk compared to placebo: 4 wk esomeprazole 50.5% versus placebo 32.2%, p= 0.009; 8 wk esomeprazole 55.1% versus placebo 46.1%, p= 0.16. A similar relationship at 4 and 8 wk was seen for symptom resolution (GOS = 1) and improvement (DeltaGOS > or =2). CONCLUSION: For the primary outcome measure of symptom relief at 8 wk, there was no statistically significant difference between esomeprazole 40 mg once a day and placebo. However, at 4 wk, esomeprazole was significantly more effective than placebo for symptom relief. The difference in therapeutic gain between 4 and 8 wk was largely due to a higher placebo response rate at 8 wk.     

Efficacy of S-Pantoprazole 20?mg Compared with Pantoprazole 40?mg in the Treatment of Reflux Esophagitis: A Randomized, Double-Blind Comparative Trial

Background

S-isomer (S) pantoprazole is known to be more effective and less dependent on cytochrome 2C19 than R-isomer (R)-pantoprazole.

Aim

The purpose of this study was to compare the efficacy and safety of S-pantoprazole 20?mg versus pantoprazole 40?mg for treatment of reflux esophagitis.

Methods

This multi-center, double-blind, randomized trial enrolled patients with endoscopically documented reflux esophagitis. Patients were assigned to receive either 20?mg S-pantoprazole or 40?mg pantoprazole once daily for 4?weeks. Endoscopy and symptoms were assessed after 4?weeks of treatment. In patients whose reflux esophagitis was not resolved at 4?weeks, treatment was extended to 8?weeks and symptoms were reassessed. Heartburn, chest pain, acid regurgitation, globus, and overall symptoms were rated. The primary efficacy endpoint was healing of esophagitis, and secondary endpoints were symptomatic and endoscopic improvement.

Results

Sixty-seven patients in the S-pantoprazole group (52 male, mean age 51?years) and 62 in the pantoprazole group (61 male, mean age 50?years) were analyzed per protocol. The healing rate of reflux esophagitis was 85?% at 4?weeks and 94?% at 8?weeks in the S-pantoprazole group, which did not differ from those in the pantoprazole group (84 and 97?%, respectively). After treatment, individual and overall gastroesophageal reflux disease (GERD) symptoms and esophagitis improved compared with baseline inflammation in both groups. Intergroup differences in symptoms and endoscopic healing were not significant.

Conclusion

The efficacy and safety of 20?mg S-pantoprazole were comparable to those of 40?mg pantoprazole for treatment of reflux esophagitis and symptomatic improvement of GERD.