Controlling on-demand gastric acidity in obese subjects: a randomized, controlled trial comparing a single dose of 20 mg rabeprazole and 20 mg omeprazole.

BACKGROUND: Obesity is associated with a risk of gastroesophageal reflux disease. The pharmacodynamic efficacy of proton pump inhibitors has not been specifically evaluated in obese subjects. The aim of this study was to compare the antisecretory response to a single oral dose of 20 mg rabeprazole, 20 mg omeprazole and placebo in obese subjects. METHODS: Gastric pH was monitored for 24 hours on three separate occasions in eighteen H. pylori-negative, asymptomatic obese subjects. Subjects were given omeprazole, rabeprazole or placebo in a randomized order and in a double-blind fashion. The main analysis criterion was 24-h percent of time post dose with intragastric pH above 3; secondary criteria were percentage of time above pH 4, median pH, [H+] concentrations and nocturnal acid breakthrough (NAB). Results were analyzed using linear mixed models and Wilks test comparing variances. RESULTS: 24-h median [IQ] percentages of time with gastric pH above 3 and 4 were higher with rabeprazole than omeprazole (46 [37-55] vs. 30 [15-55] %, 9 [5-11] % for placebo) but the differences did not reach statistical significance (p = 0.11 and 0.24, respectively). Median acid concentrations were significantly lower with rabeprazole than with omeprazole and placebo (22 [14-53] vs. 54 [19-130] and 95 [73-170] mmoles/l, p < 0.01) for all periods. The number of NAB was significantly lower with rabeprazole than with omeprazole (median 1 [1,2] vs. 2 [1-3], p = 0.04). Variances of 24-h data (pH above 3 and 4, median pH, [H+] concentrations) were significantly lower with rabeprazole than with omeprazole (p < 0.0001). CONCLUSIONS: In asymptomatic obese subjects the gastric antisecretory response to a single dose of rabeprazole and omeprazole was strong and not significantly different between drugs despite a significantly more homogeneous response with rabeprazole. TRIAL REGISTRATION: ClinicalTrial.gov: NCT01136317.

Clinical, but not oesophageal pH-impedance, profiles predict response to proton pump inhibitors in gastro-oesophageal reflux disease.

OBJECTIVE: Approximately 30% of patients with gastro-oesophageal reflux disease (GORD) do not achieve adequate symptom control with proton pump inhibitors (PPIs). The aim of this study was to determine whether any symptom profile or reflux pattern was associated with refractoriness to PPI therapy. DESIGN: Patients with typical GORD symptoms (heartburn and/or regurgitation) were included and had 24 h pH-impedance monitoring off therapy. Patients were considered to be responders if they had fewer than 2 days of mild symptoms per week while receiving a standard or double dose of PPI treatment for at least 4 weeks. Both clinical and reflux parameters were taken into account for multivariate analysis (logistic regression). RESULTS: One hundred patients were included (median age 50 years, 42 male), 43 responders and 57 non-responders. Overall, multivariate analysis showed that the factors associated with the absence of response were absence of oesophagitis (p=0.050), body mass index (BMI) ≤25 kg/m(2) (p=0.002) and functional dyspepsia (FD) (p=0.001). In patients who reported symptoms during the recording (n=85), the factors associated with PPI failure were BMI ≤25 kg/m(2) (p=0.004), FD (p=0.009) and irritable bowel syndrome (p=0.045). In patients with documented GORD (n=67), the factors associated with PPI failure were absence of oesophagitis (p=0.040), FD (p=0.003), irritable bowel syndrome (p=0.012) and BMI ≤25 kg/m(2) (p=0.029). CONCLUSION: No reflux pattern demonstrated by 24 h pH-impedance monitoring is associated with response to PPIs in patients with GORD symptoms. In contrast, absence of oesophagitis, presence of functional digestive disorders and BMI ≤25 kg/m(2) are strongly associated with PPI failure.

Epidemiology of the complications of gastroesophageal reflux disease.

The complications of gastroesophageal reflux disease (GERD) include ulcers, strictures, Barrett's esophagus and carcinoma. Although the prevalence of GERD is very high, the development of complications remains quite rare and usually occurs in association with factors generally observed in more severe disease such as hiatal hernia, bile reflux or severely disturbed motility. Recent studies have emphasized the role of obesity and genetic factors as aggravating factors in the development of GERD complications. Barrett's esophagus is the most prevalent complication of GERD and seems to be associated with an increased mortality rate. However, cancer incidence is low and most patients die from other causes, especially cardiovascular disease.