Challenging the dogma: a randomized trial of standard vs. half-dose concomitant nonbismuth quadruple therapy for Helicobacter pylori infection.

BACKGROUND: Current treatment of Helicobacter pylori consists of three or four drugs for 7-14 days with important associated cost and adverse events. AIMS: This study compared efficacy and safety of standard dose vs. half-dose concomitant nonbismuth quadruple therapy (NBQT) for 7 days. The standard dose consisted of twice daily rabeprazole 20 mg, amoxicillin 1 g, metronidazole 500 mg, and clarithromycin 500 mg. METHODS: This was a prospective randomized trial. (14)C-urea breath test was performed ≥4 weeks after treatment and ≥2 weeks off acid suppressive therapy. Compliance and adverse events were monitored during treatment. RESULTS: A total of 200 consecutive treatment-naïve patients were enrolled. Baseline characteristics were similar between groups, with 15.5% of subjects reporting prior macrolide use. Eradication occurred in 78% (95% CI 68.6-85.7%) in both groups on intention-to-treat analysis. Per-protocol rates were 82.1 vs. 83.9% for standard-dose patients vs. half-dose patients, respectively (p = NS). Adverse events (only mild) were reported in 57 vs. 41% of standard-dose patients vs. half-dose patients (p = 0.024), with metallic taste and nausea notably less frequent in the latter (36 vs. 12% and 18 vs. 7%, respectively; p < 0.05 for both). Overall, eradication failed in 38.7% of prior macrolide users vs. 18.9% without such exposure (p = 0.019). On multivariate logistic regression, prior macrolide exposure was the only factor associated with failed eradication (OR 2.60, 95% CI 1.06-6.39; p = 0.038). Treatment was cheaper with the half-dose regimen. INTERPRETATION: A 50% reduction in antibiotic dosage does not diminish efficacy of concomitant nonbismuth quadruple therapy but leads to significant reduction in cost and adverse events. Seven-day concomitant NBQT is suboptimal for H. pylori independent of prior macrolide exposure.

Prediction of celiac disease at endoscopy.

BACKGROUND AND STUDY AIMS: Celiac disease is increasingly recognized worldwide, but guidelines on how to detect the condition and diagnose patients are unclear. In this study the prevalence and predictors of celiac disease were prospectively determined in a cross-sectional sample of Lebanese patients undergoing esophagogastroduodenoscopy (EGD). PATIENTS AND METHODS: Consecutive consenting patients (n = 999) undergoing EGD answered a questionnaire and had blood taken for serologic testing. Endoscopic markers for celiac disease were documented and duodenal biopsies were obtained. The diagnosis of celiac disease was based on abnormal duodenal histology and positive serology. Risk factors were used to classify patients to either high or low risk for celiac disease. Independent predictors of celiac disease were derived via multivariate logistic regression. RESULTS: Villous atrophy (Marsh 3) and celiac disease were present in 1.8 % and 1.5 % of patients, respectively. Most were missed on clinical and endoscopic grounds. The sensitivity of tissue transglutaminase (tTG) testing for the diagnosis of villous atrophy and celiac disease was 72.2 % and 86.7 %, respectively. The positive predictive value of the deamidated gliadin peptide (DGP) test was 34.2 % and that of a strongly positive tTG was 80 %. While the strongest predictor of celiac disease was a positive tTG (odds ratio [OR] 131.7, 95 % confidence interval [CI] 29.0 - 598.6), endoscopic features of villous atrophy (OR 64.8, 95 %CI 10.7 - 391.3), history of eczema (OR 4.6, 95 %CI 0.8 - 28.8), anemia (OR 6.7, 95 %CI 1.2 - 38.4), and being Shiite (OR 5.4, 95 %CI 1.1 - 26.6) significantly predicted celiac disease. A strategy of biopsying the duodenum based on independent predictors had a sensitivity of 93 % - 100 % for the diagnosis of celiac disease, with an acceptable (22 % - 26 %) rate of performing unnecessary biopsies. A strategy that excluded pre-EGD serology produced a sensitivity of 93 % - 94 % and an unnecessary biopsy rate of 52 %. CONCLUSION: An approach based solely on standard clinical suspicion and endoscopic findings is associated with a significant miss rate for celiac disease. A strategy to biopsy based on the derived celiac disease prediction models using easily obtained information prior to or during endoscopy, maximized the diagnosis while minimizing unnecessary biopsies.

A randomized trial of standard-dose versus half-dose rabeprazole, clarithromycin, and amoxicillin in the treatment of Helicobacter pylori infection.

OBJECTIVES: To evaluate the efficacy and safety of a standard-dose versus half-dose 10-day triple regimen for the eradication of Helicobacter pylori infection. METHODS: A total of 115 consecutive patients with documented infection were enrolled in this open-label trial. Group A (standard dose) received rabeprazole (20 mg), amoxicillin (1 g), and clarithromycin (500 mg), all twice daily for 10 days. Group B (half dose) received rabeprazole (10 mg), amoxicillin (500 mg), and clarithromycin (250 mg), all twice daily for 10 days. (14)C urea breath tests were performed a minimum of 4 weeks after treatment and a minimum of 2 weeks off any acid-suppressive therapy. Compliance and adverse effects were evaluated throughout the treatment period. RESULTS: A total of 115 patients were enrolled (59 women and 56 men; mean age 47.1±14.0 years). Eradication occurred in 45 of 58 patients [77.6%; 95% confidence interval (CI): 66.9-88.3%] in the standard-dose group versus 44 of 57 in the half-dose group (77.2%; 95% CI: 66.3-88.1%) on an intent-to-treat (ITT) analysis (P=1.00). Per protocol eradication rates were 45 of 57 (78.9%; 95% CI: 68.4-85.9%) and 44 of 54 (81.5%; 95% CI: 71.1-91.8%), respectively (P=0.81). The number of patients reporting any adverse effect was significantly higher in the standard-dose group (64.9 vs. 40.4%; P=0.014). The cost of treatment was significantly less in patients receiving the half-dose regimen (ITT analysis; P<0.05). The number needed to harm to suffer one additional failure in the half-dose over the standard-dose arm was 250 (ITT analysis). CONCLUSION: A half-dose 10-day regimen of rabeprazole, amoxicillin, and clarithromycin is equally effective but cheaper and better tolerated than its standard-dose regimen in the treatment of Helicobacter pylori. Eradication rates of both regimens are, however, suboptimal compared with accepted standards.