Lansoprazole in the treatment of functional dyspepsia: two double-blind, randomized, placebo-controlled trials.

PURPOSE: The efficacy of proton pump inhibitor therapy for symptom resolution in patients with functional dyspepsia remains controversial. This study was designed to compare the efficacy of lansoprazole with placebo in relieving upper abdominal discomfort in patients with functional dyspepsia. METHODS: We enrolled 921 patients with functional dyspepsia (defined as persistent or recurrent upper abdominal discomfort during the prior 3 months) and moderate upper abdominal discomfort on at least 30% of screening days; none of the patients had predominant symptoms suggestive of gastroesophageal reflux or endoscopic evidence of erosive or ulcerative esophagitis, or gastric or duodenal ulcer or erosion. Patients were assigned randomly to receive lansoprazole 15 mg (n = 305), lansoprazole 30 mg (n = 308), or placebo (n = 308) daily for 8 weeks. Patients recorded the frequency and severity of symptoms in daily diaries. RESULTS: At week 8, significantly (P <0.001) greater mean reductions in the percentage of days with upper abdominal discomfort were reported in patients treated with lansoprazole 15 mg (35%) or 30 mg (34%) compared with those treated with placebo (19%). Similarly, more patients treated with lansoprazole 15 mg (44%) or 30 mg (44%) reported complete symptom resolution (defined as no episodes of upper abdominal discomfort in the 3 days before the study visit) at 8 weeks than did placebo-treated patients (29%, P <0.001). Improvement of upper abdominal discomfort, however, was seen only in patients who had at least some symptoms of heartburn at enrollment. CONCLUSION: Lansoprazole, at a daily dose of 15 mg or 30 mg, is significantly better than placebo in reducing symptoms of persistent or recurrent upper abdominal discomfort accompanied by at least some symptoms of heartburn.

Proton pump inhibitors: effective first-line treatment for management of dyspepsia.

The aim of this study was to evaluate the reasons for trial exclusion among dyspeptic patients and estimate the proportion that may have benefited from proton pump inhibitor (PPI) therapy. Stringent inclusion criteria for enrollment in two multicenter functional dyspepsia trials included dyspepsia (predominant persistent/recurrent upper abdominal discomfort [UAD] during the prior 3 months) of at least moderate intensity during > or =30% of days during the prior 2 to 3 weeks. Exclusion criteria were mild/infrequent UAD; heartburn and UAD of equal frequency; predominant heartburn with UAD; endoscopic evidence of erosive esophagitis or Barrett's or gastric and/or duodenal erosions (>5) or ulcers; irritable bowel syndrome (IBS); other gastrointestinal diagnoses; or other "non-categorized" disorders. Of 2,588 screened patients, 1,667 were excluded. Excluded patients by category had mild/infrequent UAD (12.5%, n=324), heartburn and UAD of equal frequency (1.1%, n=29), predominant heartburn with UAD (11.6%, n=300), endoscopic evidence of erosive esophagitis or Barrett's (6.2%, n=160), gastric and/or duodenal erosions (1.4%, n=36), gastric and/or duodenal ulcers (2.0%, n=53), IBS (7%, n=180), "other" gastrointestinal diagnoses (2.8%, n=73), or other "non-categorized" disorders (19.8%, n=512). Fifty-four percent of patients (902/1,667) had symptoms/diagnoses that would be expected to improve with PPI therapy. Individuals with IBS, "other," or "non-categorized" disorders were considered to have symptoms unlikely to respond to PPI treatment. Empiric PPI treatment would be expected to provide symptom relief to the majority of dyspepsia sufferer who present in clinical practice. PPIs represent the best currently available therapy for acid-related disorders and should be considered the first-line management approach in patients with uninvestigated dyspepsia.

Failures in a proton pump inhibitor therapeutic substitution program: lessons learned.

The pathogenesis of patient dissatisfaction following involuntary therapeutic substitutions involving proton pump inhibitors (PPIs) is poorly understood. The aim of this study was to describe the patient population experiencing therapeutic failure and investigate whether failure was related to individual differences in response to the different PPIs. Treatment failures in a lansoprazole-rabeprazole therapeutic substitution program were compared to switch successes. A subgroup was randomized in a double-blind, double-dummy, crossover study to four 2-week periods of lansoprazole-rabeprazole-lansoprazole-rabeprazole or vice versa. Measures included overall rating of gastrointestinal reflux disease (GERD) symptoms for the past week as well as the frequency and distress scales of the GERD Symptom Assessment Scale. One hundred fifteen nonresponders were compared with 54 successful responders. Nonresponders consisted primarily of patients with GERD (74%, vs. 44% of responders; P = 0.005) who had undergone upper gastrointestinal endoscopy (50%, vs. 31% of responders; P = 0.02). Twelve patients completed the randomized treatment study. The interrater kappa coefficient for responder status was estimated to be 0.80 for lansoprazole and 0.21 for rabeprazole. The majority of PPI nonresponders had a clinical diagnosis of GERD and were receiving >/=40 mg of rabeprazole daily. This pilot study provides new insights into the design of subsequent studies of nonresponders in PPI therapeutic substitution programs.

Risk factors for Helicobacter pylori resistance in the United States: the surveillance of H. pylori antimicrobial resistance partnership (SHARP) study, 1993-1999.

BACKGROUND: Pretreatment antimicrobial resistance has an important impact on the efficacy of many Helicobacter pylori treatment regimens. OBJECTIVE: To estimate the prevalence of H. pylori resistance to antimicrobials in the United States, to characterize risk factors associated with H. pylori antimicrobial resistance, and to explore the association between drug utilization and antimicrobial resistance patterns over time. DESIGN: Meta-analysis using patient-level data. SETTING: 20 nationwide trials of H. pylori eradication. PATIENTS: 3624 men and women, each of whom contributed one isolate. MEASUREMENTS: Rates of H. pylori resistance to clarithromycin, metronidazole, and amoxicillin, according to geographic region, age, sex, study year, ethnicity, ulcer status, test method, and study. RESULTS: Overall resistance to clarithromycin, metronidazole, and amoxicillin was 10.1% (95% CI, 9.1% to 11.1% [360 of 3571 patients]), 36.9% (CI, 35.1% to 38.7% [1063 of 2883 patients]), and 1.4% (CI, 1.0% to 1.8% [48 of 3486 patients]), respectively. In multivariable analyses, multiple risk factors were associated with resistance to individual agents. Clarithromycin resistance was significantly associated with geographic region (P = 0.050), older age (P < 0.001), female sex (P < 0.001), inactive ulcer disease (P < 0.001), and study (P = 0.010). Metronidazole resistance was significantly associated with female sex (P < 0.001), earlier year of study enrollment (P = 0.036), Asian ethnicity (P < 0.001), use of an epsilometer test (P = 0.002), and study (P < 0.001). Amoxicillin resistance was low and was not significantly associated with any risk factor. In the 1990s, when rates for use of oral macrolides and metronidazole were relatively stable, clarithromycin resistance rates were stable and metronidazole resistance rates varied. CONCLUSIONS: Clinicians should consider risk factors for antimicrobial resistance when deciding which patients should have susceptibility testing and when choosing appropriate H. pylori treatments in the empirical setting.