Comparison of sequential and standard triple-drug regimen for Helicobacter pylori eradication: a 14-day, open-label, randomized, prospective, parallel-arm study in adult patients with nonulcer dyspepsia.

BACKGROUND: The eradication rates of Helicobacter pylori with standard treatments are decreasing worldwide.
OBJECTIVES: The primary aim of this study was to compare the eradication success of a 14-day sequential regimen with proton pump inhibitor (PPI)-based triple treatment. The secondary objectives of the study were to evaluate the effect of gastritis score and smoking on eradication rates as well as evaluation of compliance and tolerability of both regimens.
METHODS: Consecutive H pylori-positive patients with nonulcer dyspepsia were randomized into 1 of 2 groups in this 14-day, open-label, randomized, prospective, parallel-arm study. An upper endoscopy with biopsy and (14)C-urea breath test ((14)C-UBT) were performed before enrollment. The first group was administered a sequential regimen consisting of pantoprazole 40 mg and amoxicillin 1 g for 7 days, followed by pantoprazole 40 mg, tetracycline 500 mg, and metronidazole 500 mg for the next 7 days. The second group was administered pantoprazole 40 mg, amoxicillin 1 g, and clarithromycin 500 mg (PAC group) for 14 days. All drugs were administered BID, with the exception of tetracycline, which was administered QID. Eradication was confirmed by (14)C-UBT 6 weeks after the end of the treatment. Histologic examination and (14)C-UBT were conducted by investigators blinded to the protocols. Patients were asked to report any adverse events (AEs) during the treatment period.
RESULTS: Three hundred white patients were enrolled in the study and evenly randomized into the sequential treatment group (98 males and 52 females; mean age, 40.2 years) and the PAC group (86 males and 64 females; mean age, 41.2 years). A total of 274 patients completed the study per protocol (PP). Twenty-six patients discontinued: lost to follow-up (16), withdrawn due to AEs (9); and noncompliance (1). The intent-to-treat (ITT) and PP H pylori eradication rates were 72.6% and 80.1% in the sequential group, and 58% and 63% in the PAC group, respectively. The eradication rate was significantly higher in the sequential group compared with the PAC group in both the ITT and PP populations (P=0.01 and P=0.002, respectively). The eradication rates were higher in nonsmoking patients compared with smoking patients both in the sequential group (85.8% vs 70.5%) and the PAC group (67.7% vs 53.3%), but the results were not statistically significant when the groups were analyzed separately. Overall, 32 patients (10.7%) reported an AE. Treatment was discontinued in 9 patients because of serious AEs (sequential group--abdominal pain [2 patients], diarrhea [1], chest pain [1], and vaginal pruritus [1]; PAC group--nausea/vomiting [2], chest pain [1], and numbness [1]). There were no significant between-group differences in regard to compliance or AEs. Univariate analyses found no significant effect of sex, age, alcohol consumption, antacid usage, or gastritis score on the eradication rates.
CONCLUSIONS: A 14-day sequential treatment regimen achieved a significantly higher eradication rate of H pylori compared with standard PPI-based triple regimen in this small selected population. Large, double-blind, controlled studies are needed to confirm these results.

RCT Entities:   Population Interventions Outcomes