Randomized Controlled Trial Comparing 7-Day Triple, 10-Day Sequential, and 7-Day Concomitant Therapies for Helicobacter pylori Infection

Abstract

e With the rising prevalence of antimicrobial resistance, the failure rate of the standard triple therapy for Helicobacter pylori infection is increasing. Sequential therapy and concomitant therapy have been recommended to replace standard triple therapy for H. pylori eradication in regions with high clarithromycin resistance. The aim of this prospective, randomized, and controlled study was to simultaneously assess the efficacies of 10-day sequential and 7-day concomitant therapies versus a 7-day standard triple therapy for treating H. pylori infection. Consecutive H. pylori-infected subjects were randomly assigned to a 7-day standard triple therapy (pantoprazole, clarithromycin, and amoxicillin for 7 days), a 10-day sequential therapy (pantoprazole and amoxicillin for 5 days, followed by pantoprazole, clarithromycin, and metronidazole for a further 5 days), or a 7-day quadruple therapy (pantoprazole, clarithromycin, amoxicillin, and metronidazole for 7 days). H. pylori status was confirmed 6 weeks after therapy. Three hundred seven H. pylori-infected participants were randomized to receive triple (n ‫؍‬ 103), sequential (n ‫؍‬ 102), or concomitant (n ‫؍‬ 102) therapies. The eradication rates by an intention-to-treat analysis in the three treatment groups were 81.6% (95% confidence interval [CI], 74.1% to 89.0%), 89.2% (95% CI, 83.2% to 95.2%), and 94.1% (95% CI, 89.5% to 98.7%). The seven-day concomitant therapy had a higher eradication rate than did the 7-day triple therapy (difference, 12.5%; 95% CI, 3.7% to 21.3%). There were no significant differences in the eradication rates between the sequential and standard triple therapies. All three treatments exhibited similar frequencies of adverse events (8.7%, 8.8%, and 13.7%, respectively) and drug compliance (99.0%, 98.0%, and 100.0%, respectively). In conclusion, the seven-day concomitant therapy is superior to the 7-day standard triple therapy for H. pylori eradication. Additionally, it is less complex than the 10-day sequential therapy because the drugs are not changed halfway through the treatment course. (This study has been registered at ClinicalTrials.gov under registration no. NCT1769365.)

Comparison of three different regimens against Helicobacter pylori as a first-line treatment: A randomized clinical trial

“…There was no difference in the effect of CT in clarithromycin-sensitive and resistant groups [38] as well as in metronidazole-sensitive and resistant groups [39]. Several studies showed that there was no difference in the effectiveness of CT and ST in clarithromycin and metronidazole-sensitive or resistant groups [40,41]. Moreover, this study showed that eradication rates of these two therapies were similar, too.…”

Ensuring the highest eradication rates in H. pylori: the case of non-bismuth quadruple concomitant therapy

“…The data provided by Georgopoulos et al can be compared to those published in previous studies [25][26][27][28], in which the relative efficacy of concomitant regimen was consistently and significantly superior to that of sequential therapy throughout all the resistance profiles. If we pool previous data, concomitant offers a 15% benefit (risk difference) in clarithromycin-resistant patients, a 14% in the case of metronidazole resistance and, finally, a 38% in dual resistance.…”

Helicobacter pylori infection: A recent approach to diagnosis and management

“…In a multicenter prospective RCT conducted in a high clarithromycin resistant area, concomitant therapy (esomeprazole, 40 mg; amoxicillin, 1 mg; clarithromycin, 500 mg; metronidazole, 500 mg bid*10d) had significantly higher eradication rates of 89% and 93.4% (versus 78.7%/82.8% of sequential therapy) according to ITT and PP analyses, respectively, despite drug resistances (metronidazole, 34%; clarithromycin, 27%; and dual drugs ,7.9%) on culture [9]. In another study, 7 days of concomitant therapy (pantoprazole, 40 mg; amoxicillin, 1 mg; clarithromycin, 500 mg; metronidazole, 500 mg bid) showed eradication rates of 94.1%, which was significantly higher compared to that of 7-day standard triple therapy (81.6%) and 10-day sequential therapy (89.2%) [65]. Additionally, 7-day concomitant therapy (Rebeprazole, amoxicillin, clarithromycin, metronidazole) showed eradication rates of 90.3% [57].…”

“…In another study with omeprazole, 20 mg; amoxicillin, 1 gm; clarithromycin, 500 mg; and tinidazole, 500 mg for 14 day, the eradication rates were 86.3% and 95% according to ITT and PP analyses, respectively [60], whereas the 5-day treatment showed eradication rates of 85.5% and 91.6% according to ITT and PP analyses, respectively [62]. Therefore, these therapies with 7-14 day durations can be an alternative to sequential therapy in high drug resistance areas and also in settings where bismuth is not available [9,57,62,65,66].…”