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.     

Esomeprazole (40 mg) compared with lansoprazole (30 mg) in the treatment of erosive esophagitis

OBJECTIVES: Esomeprazole, the S isomer of omeprazole, has been shown to have higher healing rates of erosive esophagitis than omeprazole. This study compared esomeprazole with lansoprazole for the healing of erosive esophagitis and resolution of heartburn. METHODS: This United States multicenter, randomized, double blind, parallel group trial was performed in 5241 adult patients (intent-to-treat population) with endoscopically documented erosive esophagitis, which was graded by severity at baseline (Los Angeles classification). Patients received 40 mg of esomeprazole (n = 2624) or 30 mg of lansoprazole (n = 2617) once daily before breakfast for up to 8 wk. The primary efficacy endpoint was healing of erosive esophagitis at week 8. Secondary assessments included proportion of patients healed at week 4, resolution of investigator-recorded heartburn, time to first and time to sustained resolution of patient diary-recorded heartburn, and proportion of heartburn-free days and nights. RESULTS: Esomeprazole (40 mg) demonstrated significantly higher healing rates (92.6%, 95% CI = 91.5-93.6%) than lansoprazole (30 mg) (88.8%, 95% CI = 87.5-90.0%) at week 8 (p = 0.0001, life-table estimates, intent-to-treat analysis). A significant difference in healing rates favoring esomeprazole was also observed at week 4. The difference in healing rates between esomeprazole and lansoprazole increased as baseline severity of erosive esophagitis increased. Sustained resolution of heartburn occurred faster and in more patients treated with esomeprazole. Sustained resolution of nocturnal heartburn also occurred faster with esomeprazole. Both treatments were well tolerated. CONCLUSIONS: Esomeprazole (40 mg) is more effective than lansoprazole (30 mg) in healing erosive esophagitis and resolving heartburn. Healing rates are consistently high with esomeprazole, irrespective of baseline disease severity.     

Long-Term Efficacy of Lansoprazole in Preventing Relapse of Erosive Reflux Esophagitis

In a phase III study of lansoprazole treatment, patients with healed or unhealed erosive esophagitis entered a titrated open-label treatment period and received lansoprazole for ≤6 years to assess long-term maintenance therapy. Doses were adjusted depending on symptom response. Endoscopy was performed yearly. One hundred ninety-five subjects received lansoprazole for <1 to 72 months; most received daily doses of ≤30 mg. Lansoprazole maintained erosive esophagitis remission in 75% of subjects receiving treatment for ≤72 months, with 39 subjects experiencing 50 recurrences. Most subjects (94–95%) had no or mild symptoms of day or night heartburn at study end, and 77% were asymptomatic at first erosive esophagitis recurrence. The most common treatment-related adverse events included diarrhea (10%), headache (8%), and abdominal pain (6%), and were mild or moderate in severity. Long-term lansoprazole is effective and well tolerated when used to maintain erosive esophagitis remission for ≤6 years.     

Esomeprazole once daily for 6 months is effective therapy for maintaining healed erosive esophagitis and for controlling gastroesophageal reflux disease symptoms: a randomized, double-blind, placebo-controlled study of efficacy and safety

OBJECTIVE: Esomeprazole, the S-isomer of omeprazole, achieves a significantly greater healing rate and symptom resolution of erosive esophagitis than that achieved by omeprazole. The objective of this study is to assess the efficacy of the new proton pump inhibitor esomeprazole in preventing relapse over a prolonged period in patients with healed erosive esophagitis. METHODS: A total of 318 gastroesophageal reflux patients whose erosive esophagitis was healed in a comparative study of esomeprazole 40 mg, 20 mg, or omeprazole 20 mg, were randomized to maintenance therapy with once daily esomeprazole 40 mg, 20 mg, or 10 mg, or placebo in a U.S., double-blind multicenter trial. RESULTS: After 6 months, healing was maintained (cumulative life table rates) in 93.6% (95% CI 87.4-99.7) of patients treated with esomeprazole 40 mg, 93.2% (95% CI 87.4-99.0) treated with esomeprazole 20 mg, and 57.1% (95% CI 45.2-69) treated with esomeprazole 10 mg; p < 0.001 vs placebo (29.1%; 95% CI 17.7-40.3). Of patients relapsing, mean time to first recurrence of esophagitis increased with dose, from 34 days (placebo) to 78 days (10 mg), 115 days (20 mg), and 163 days (40 mg). Patients treated with esomeprazole had less frequent and less severe heartburn than those treated with placebo. At month 6, more than 70% of patients being treated with esomeprazole remained symptom-free. CONCLUSIONS: Esomeprazole is effective and well tolerated in the maintenance of a healing erosive esophagitis. Esomeprazole 40 mg and 20 mg maintain healing in over 90% of patients while providing effective control of heartburn symptoms.     

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.     

A Multicenter, Randomized, Double-Blind, 8-Week Comparative Trial of Standard Doses of Esomeprazole (40 mg) and Omeprazole (20 mg) for the Treatment of Erosive Esophagitis

To compare esomeprazole with omeprazole for healing erosive esophagitis (EE), 1148 patients with endoscopically confirmed EE were randomized to once-daily esomeprazole, 40 mg, or omeprazole, 20 mg, for 8 weeks in this multicenter, double-blind, parallel-group trial. The primary outcome was the proportion of patients with healed EE at week 8. Secondary outcomes included diary and investigator assessments of heartburn symptoms. At week 8, estimated healing rates were 92.2% (95% CI, 89.9%–94.5%) with esomeprazole and 89.8% (95% CI, 87.2%–92.4%) with omeprazole. Healing rates with esomeprazole were significantly higher than those with omeprazole at weeks 8 (88.4% vs 77.5%; P = 0.007) and 4 (60.8% vs 47.9%; P = 0.02) in patients with moderate to severe (Los Angeles grade C or D) EE at baseline but were not significantly different for patients with mild (Los Angeles grade A or B) EE. Both treatments were comparable for other secondary measures and had similar tolerability profiles.An erratum to this article can be found at     

Symptom response and healing of erosive esophagitis with proton-pump inhibitors in patients with Helicobacter pylori infection

OBJECTIVES: The aim of this article is to determine the severity of esophagitis and the response to treatment with proton-pump inhibitors in patients with and without evidence of Helicobacter pylori infection. METHODS: This retrospective analysis evaluated data collected in a randomized, double-blind clinical trial that assessed the efficacy and safety of once-daily esomeprazole 40 mg (n = 2,624) versus lansoprazole 30 mg (n = 2,617) for up to 8 wk in the treatment of reflux-associated erosive esophagitis. At baseline, erosive esophagitis was graded using the Los Angeles (LA) classification; serologic testing for H. pylori was performed using a FlexSure HP serum test. RESULTS: There were 14.7% of patients who were seropositive for H. pylori. The percentages of seropositive and seronegative patients with each grade of esophagitis were: LA grade A, 38%, 36%; LA grade B, 41%, 39%; LA grade C, 16%, 19%; and LA grade D, 5%, 6%, respectively. Severe heartburn was present at baseline in 42% of H. pylori-positive and 42% of H. pylori-negative patients. Life-table healing rates with esomeprazole were not influenced by H. pylori status (seropositive 92.6% (95% confidence interval: 89.8-95.4); seronegative 92.6% (95% confidence interval: 91.4-93.7)). The rates with esomeprazole were significantly higher than those with lansoprazole (seropositive 90.5% (95% confidence interval: 87.5-93.5); seronegative 88.5% (95% confidence interval: 87.1-89.8)) after adjusting for baseline H. pylori status (p = 0.001). CONCLUSIONS: The severity of erosive esophagitis at baseline was similar regardless of H. pylori seropositivity. Healing rates were not influenced by H. pylori status.     

Maintenance therapy for erosive esophagitis in children after healing by omeprazole: is it advisable?

OBJECTIVES: To evaluate the efficacy of acid-suppressive maintenance therapy for gastroesophageal reflux disease (GERD) in children, after the healing of reflux esophagitis. METHODS: Forty-eight children (median age 105 months, range 32-170) with erosive reflux esophagitis were initially treated with omeprazole 1.4 mg/kg/day for 3 months. Patients in endoscopic remission were assigned in a randomized, blinded manner by means of a computer-generated list to three groups of 6-month maintenance treatment: group A (omeprazole at half the starting dose, once daily before breakfast), group B (ranitidine 10 mg/kg/day, divided in two doses), and group C (no treatment). Endoscopic, histological, and symptomatic scores were evaluated at: T0, enrollment; T1, assessment for remission at 3 months after enrollment (healing phase); T2, assessment for effective maintenance at 12 months after T0 (3 months after the completion of the maintenance phase). Relapse was defined as the recurrence of macroscopic esophageal lesions. After the completion of the maintenance phase, patients without macroscopic esophagitis relapse were followed up for GERD symptoms for a further period of 30 months. RESULTS: Of 48 initially treated patients, 46 (94%) healed and entered the maintenance study. For all patients, in comparison to T0, the histological, endoscopic, and symptomatic scores were significantly reduced both at T1 and T2 (P<0.0001, for each). No significant difference was found in these three scores, comparing group A, B, and C at T1 and T2. A relapse occurred in one patient only, who presented with macroscopic esophageal lesions at T2. Three months after the completion of the maintenance phase, 12 (26%) patients complained of symptoms sufficiently mild to discontinue GERD therapy, excluding the patient who showed macroscopic esophagitis relapse. Three of 44 (6.8%) patients reported very mild GERD symptoms within a period of 30 months after maintenance discontinuation. CONCLUSIONS: Our pediatric population showed a low rate of erosive esophagitis relapse and GERD symptom recurrence long term after healing with omeprazole, irrespective of the maintenance therapy.     

奥美拉唑、泮托拉唑、兰索拉唑和埃索美拉唑对反流性食管炎患者症状缓解的比较研究

目的比较奥美拉唑、泮托拉唑、兰索拉唑和埃索美拉唑对反流性食管炎患者症状缓解之间的差异。方法320例内镜诊断为反流性食管炎患者被随机分为4组,并分别服用奥美拉唑20mg,1次／d,8周;兰索拉唑30mg,1次／d,8周;泮托拉唑40mg,1次／d,8周;埃索美拉唑40mg,1次／d,8周。用six—point scale（0：无,1：轻度,2：轻度-中度,3：中度,4：中度-重度,5：重度）评价服用4种质子泵抑制剂后7天内的烧心和反流症状。结果埃索美拉唑组的平均烧心积分比其他质子泵抑制剂下降更迅速。埃索美拉唑组第1～5天的烧心症状完全消失率明显高于奥美拉唑组（P值分别为0．0054、0．0072、0．0089、0．0107、0．0134）、兰索拉唑组（P值分别为0．0043、0．0034、0．0044、0．0011、0．0052）、泮托拉唑组（P值分别为0．0156、0．0003、0．0005、0,0024、0．0172）。内镜下反流性食管炎愈合率4组之间无明显差异。结论埃索美拉唑比奥美拉唑、兰索拉唑、泮托拉唑更迅速地减轻反流性食管炎患者的烧心和反流症状。     

Selection of patients for successful maintenance treatment of esophagitis with low-dose omeprazole: use of 24-hour gastric pH monitoring

OBJECTIVE: Treating patients with erosive esophagitis and maintaining remission in a cost-effective fashion is a desirable goal in clinical practice. There are no established criteria to identify patients with healed esophagitis who will subsequently remain in remission with low-dose omeprazole therapy. We investigated whether 24-h esophageal-gastric pH monitoring could provide criteria to select patients for low-dose omeprazole maintenance therapy. METHODS: Seventy consecutive symptomatic outpatients with grade 2-3 reflux esophagitis were prospectively investigated. They were treated with 20 mg/day omeprazole for 2 months. Those with healed esophagitis were given alternate-evening 20-mg omeprazole maintenance therapy for 6 months. Clinical evaluation, endoscopy, and 24-h esophageal-gastric pH were done at the end of each treatment period. Results of pH studies of patients in remission were compared with those with endoscopically documented relapse of esophagitis. RESULTS: In 63/70 patient (intention-to-treat, 90%; 95% confidence interval [CI], 83-97%) esophagitis was healed at 2 months. During the 6-month maintenance period esophagitis remain healed in 28 (G1) (40%; 95% CI, 29-52%), but recurred in 32 patients (G2). During healing with omeprazole 20 mg/day the 24-h gastric pH was below 4 for <10% of the time in 96% of the patients, who subsequently remained in long-term remission with low-dose maintenance therapy (G1), but not in any patient with recurrence of esophagitis (G2). The 10% threshold value has a specificity of 1.00 and sensitivity of 0.96. CONCLUSIONS: The 24-h intragastric pH monitoring during 20 mg/day omeprazole therapy provides criteria by which to preselect patients with reflux esophagitis who will remain in remission with low-dose omeprazole 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.     

Minimal change esophagitis: prospective comparison of endoscopic and histological markers between patients with non-erosive reflux disease and normal controls using magnifying endoscopy

INTRODUCTION: More than half the patients with gastroesophageal reflux disease (GERD) show no endoscopic abnormality or minimal change esophagitis (non-erosive reflux disease, NERD). We investigated the value of endoscopic and histological markers for the prediction of NERD before and after treatment with 20 mg esomeprazole. METHODS: Between July and October 2002, consecutive patients presenting for upper endoscopy were stratified into GERD and non-reflux patients (control group) with the help of a questionnaire. The endoscopist was blind to the presence of reflux symptoms. Using magnifying endoscopes minimal change esophagitis was defined by the presence of vascular injection or vascular spots above the Z-line, villous mucosal surface and islands of squamous cell epithelium below the Z-line. Targeted and random biopsies were taken below and above the Z-line. Patients with endoscopically visible classical signs of esophagitis (Los Angeles A-D) or histologically proven Barrett's esophagus were not further investigated in the study (drop out). The esophageal specimens were histologically evaluated for erosions, infiltration with leukocytes, hyperplasia of basal cells and length of papillae. Patients with NERD were treated with 20 mg esomeprazole/day for 4 weeks and reevaluated by endoscopy as described before. RESULTS: 39 patients with heartburn and 39 patients without reflux symptoms (controls) were finally included in the analysis (per protocol). Patients with NERD significantly (p = 0.005) more often showed endoscopic signs of minimal change esophagitis (27/39) than the control group (8/39). An increased length of papillae (14/39 versus 2/39; p = 0.005) and basal cell hyperplasia (17/39 versus 4/39; p = 0.009) were significantly more common in the heartburn group. After treatment with esomeprazole, no significant endoscopic or histological differences between the NERD and control group could be observed. CONCLUSIONS: Minimal change esophagitis can be seen with high resolution magnifying endoscopy. By combining endoscopic and histological markers NERD can be predicted with a sensitivity of 62% and a specificity of 74%. Treatment with esomeprazole for 4 weeks reverses the slight alterations to normal.     

Clinical Symptoms in Endoscopic Reflux Esophagitis: Evaluation in 8031 Adult Subjects

This study aimed to evaluate the correlation between symptoms and endoscopic findings in reflux esophagitis. Subjects, 8031 persons without medication for gastrointestinal disease, were briefly asked about the presence of heartburn, dysphagia, odynophagia, and acid regurgitation by associated medical staff before endoscopy for assessment of esophagitis utilizing the Los Angeles Classification. Endoscopically, 1199 (14.9%) were classified as positive reflux esophagitis, and 2223 (27.7%) had heartburn, 1522 (19.0%) had dysphagia, 493 (6.1%) had odynophagia, and 1466 (18.3%) had acid regurgitation. Multivariate analysis indicated that the symptom most related to esophagitis was heartburn (odds ratio: 2.46), although approximately 40% of subjects with grade C or D did not complain of heartburn. Regarding the other symptoms, less than 30% subjects with severe esophagitis complained of the symptoms and the odds ratio was approximately 1. These results indicate that endoscopic esophagitis was not equivalent to any reflux symptoms from which subjects suffered in their daily lives.     

The impact of body mass index on the application of on-demand therapy for Los Angeles grades A and B reflux esophagitis

BACKGROUND AND AIMS: Patients with Los Angeles grade A or B reflux esophagitis (RE-AB) can potentially be switched from active-phase therapy to on-demand esomeprazole as maintenance therapy. Body mass index (BMI) correlates significantly with reflux symptoms. We investigated whether BMI affects the efficacy of esomeprazole in active-phase or subsequent on-demand therapy. METHODS: Three hundred fifty patients with RE-AB were prospectively enrolled to receive an 8-wk course of esomeprazole (40 mg/day) as active-phase therapy. Based on the daily severity of acid regurgitation and heartburn, the cumulative proportions of patients with sustained symptomatic response (SSR), defined as free from symptoms for the last 7 days, were compared among different BMI groups (control: BMI <25 kg/m2, overweight: BMI 25-30 kg/m2, obese: BMI >30 kg/m2). In patients who had achieved SSR by week 8, on-demand therapy for 2 months was started. The number of 40-mg esomeprazole tablets used per 4-wk period was recorded. RESULTS: SSR rates were lower in both the overweight and obese groups than in the control group (P < 0.001). During on-demand therapy, the mean number of tablets used per 4-wk period was lower in the control group than in either the overweight or the obese group (13.2 vs 15.3 or 16.2, P < 0.05). The failure rate of on-demand therapy increased with increasing BMI-2.4%, 5.3%, and 14.2%, respectively, for the control, overweight, and obese groups (P= 0.002). CONCLUSION: For RE-AB, a higher BMI decreases the rate of SSR after 8-wk of esomeprazole therapy, and increases the need for medication and the failure rate of on-demand therapy.     

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.     

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.     

Efficacy and safety of esomeprazole compared with omeprazole in GERD patients with erosive esophagitis: a randomized controlled trial

OBJECTIVE: In patients with gastroesophageal reflux disease (GERD), esomeprazole, the S-isomer of omeprazole, has demonstrated pharmacological and clinical benefits beyond those seen with the racemic parent compound. This study was designed to further evaluate the efficacy and tolerability of esomeprazole relative to that of omeprazole in healing erosive esophagitis and resolving accompanying symptoms of GERD. METHODS: Esomeprazole 40 mg was compared with omeprazole 20 mg once daily in 2425 patients with erosive esophagitis (Helicobacter pylori negative by serology) in an 8-wk, multicenter, randomized, double-blind, parallel-group study conducted in 163 centers throughout the US. The primary efficacy endpoint was the proportion of patients with healed esophagitis at wk 8. Secondary endpoints were the proportion of patients healed at wk 4, resolution of heartburn at wk 4, time to first resolution and sustained resolution of heartburn, and proportion of heartburn-free days and nights. Safety and tolerability were also assessed. RESULTS: Significantly more patients were healed with esomeprazole versus omeprazole at wk 8 (93.7% vs 84.2%, p < 0.001; life table estimates, intention-to-treat analysis). Healing rates at wk 4 were 81.7% and 68.7%, respectively. Esomeprazole was superior to omeprazole for all secondary measures and had a similar safety profile. The most common adverse events in both treatment groups were headache, diarrhea, and nausea. CONCLUSIONS: Esomeprazole demonstrates significantly greater efficacy than omeprazole in the treatment of GERD patients with erosive esophagitis. The tolerability and safety of esomeprazole are comparable to that of omeprazole. (Am     

Daily low-dose versus alternate day full-dose lansoprazole in the maintenance treatment of reflux esophagitis

OBJECTIVE: For the long term maintenance treatment of reflux esophagitis several strategies have been proposed with the aim of reducing the daily dosage or the frequency of drug administration. However, the available clinical studies are scarce and are often not controlled or conducted on a reduced number of cases. We aimed to compare the efficacy of two doses of lansoprazole (15 mg once daily and 30 mg on alternate days) in maintaining endoscopic healing and symptom relief over a 6-month period. METHODS: One hundred thirty-seven patients with Savary-Miller grades I-III reflux esophagitis healed after an 8-wk treatment with lansoprazole (30 mg daily) were divided into two main groups for a 6-month maintenance therapy period: lansoprazole, 15 mg once daily (group 15qd) and lansoprazole, 30 mg on alternate days (group 30qod). These two main groups were further subdivided according to the time of drug administration; morning (15qdm and 30qodm) and evening (15qde and 30qode). Each patient underwent esophagogastroduodenoscopy before entry into the study, after 8 wk of acute therapy, and after 6 months of maintenance therapy; 24-h esophageal-gastric pH monitoring was performed at baseline and during the last week of maintenance therapy. RESULTS: At the end of the maintenance period the recurrence of esophagitis was observed in 12.1% of group 15qd patients and in 19.0% of group 30qod patients, without significant differences between the two groups. The frequency of patients without reflux symptoms after the 6-month period was the same for both groups; however, a significant increase of heartburn was observed in group 30qod patients (from 12.1% to 28.6%, p = 0.007). The time of drug administration (morning and evening) had no influence on the outcome of treatment. Both regimens significantly reduced esophageal acid exposure time and increased the median 24-h gastric pH. CONCLUSIONS: Both long term lansoprazole regimens are equally effective in preventing the recurrence of esophagitis, independent of the modality of drug administration. The daily administration seems to have a better effect on the prevention of symptom recurrence.     

Endoscopic reflux esophagitis in patients with upper abdominal pain-predominant dyspepsia

BACKGROUND: Reflux symptom assessment had reliable accuracy in the diagnosis of gastroesophageal reflux disease (GERD). However, patients may recognize heartburn or regurgitation as dyspepsia because of inaccurate understanding or atypical presentation. The aim of the present study was to estimate endoscopic reflux esophagitis in patients with upper abdominal pain as a predominant symptom in the absence of heartburn or regurgitation. METHODS: Two hundred and sixty-three consecutive patients presenting dyspepsia without heartburn or regurgitation were enrolled. Patients with heartburn or regurgitation were excluded using the symptom interviewer method. Dyspepsia was categorized into pain-predominant or dysmotility-predominant groups according to the Rome II proposal. Endoscopic reflux esophagitis was graded using the Los Angeles classification. RESULTS: One hundred and five patients were included in the pain-predominant group and 119 in the dysmotility-predominant group. Reflux esophagitis was found in 18.8% (42/224) of all dyspeptic patients. Grade A esophagitis was noted in 27.6% (29/105) of the pain-predominant group and in 7.6% (9/119) of the dysmotility-predominant group. Grade B was noted in two patients in each group. A total of 29.5% (31/105) and 9.3% (11/119) had reflux esophagitis, respectively (P < 0.001). Comparing patients with or without reflux esophagitis, there was no difference in body mass index, smoking habit, alcohol consumption, or Helicobacter pylori infection status. CONCLUSIONS: A significant proportion of patients presenting dyspepsia, especially pain-predominant dyspepsia, have endoscopic reflux esophagitis. In view of GERD, pain-predominant dyspepsia should be investigated and managed differently from dysmotility-predominant dyspepsia.     

Clinical and endoscopic evaluation of gastroesophageal reflux disease in patients successfully treated with esomeprazole

BACKGROUND: Esomeprazole, an S-isomer of omeprazole, is the first proton pump inhibitor developed as an optical isomer, and it has shown high healing rates in erosive esophagitis. AIM: To evaluate the efficacy and tolerability of esomeprazole in subjects with erosive esophagitis, according to the Los Angeles classification study design: an open, multi-center clinical study. MATERIAL AND METHODS: Two hundred and eighteen subjects with reflux esophagitis confirmed by endoscopy were included in an open, multi-center study in Brazil. All of them received esomeprazole 40 mg, once daily, for a 4-week period. Subjects who had unhealed esophagitis by week 4 continued the treatment for another 4 weeks. The primary efficacy endpoint was the healing rates by weeks 4 and 8. The secondary endpoints were the number of patients with symptom resolution by week 4, the number of days to sustained symptom resolution, number of symptom-free days and nights and safety and tolerability of the drug. RESULTS: Healing rates by weeks 4 and 8 were 82% (confidence interval: 77.4%-87.6%) and 96.1% (confidence interval: 93.5% - 98.8%), respectively. Ninety-nine (99%) of the patients had heartburn resolution by week 2. The most common adverse events were headache (4%), diarrhea (2.6%) and epigastric pain (2.2%). CONCLUSION: For the studied period, esomeprazole was shown to be a safe and well-tolerated drug, providing significant healing rates of mucosal breaks, regardless of LA classification, in patients with erosive esophagitis. Esomeprazole was also shown to be effective in quickly relieving symptoms.