“Concomitant” or “sequential” eradication of Helicobacter pylori: which regimen comes first?

“Sequential” or “concomitant” non-bismuth quadruple regimens are currently recommended by the recent updated (Maastricht IV) European guidelines as alternative to bismuth based quadruple regimen first line therapies, in areas with a high rate (over 20%) of clarithromycin resistance [1]. Besides this, there is no trial comparing both regimens in settings with increasing rates of clarithromycin resistance [2]. In a recent prospective, randomized, multicenter, clinical trial, conducted in Spain, McNicholl et al aimed to compare the effectiveness and safety of these therapies for Helicobacter pylori (H. pylori) eradication [3]. They included a large number of patients (n=338) with non-investigated/functional dyspepsia (80%) or peptic ulcer disease (20%), naive to eradication therapy. Mean age was 47 years, 60% were women and 20% smokers. They were randomly assigned to sequential treatment; omeprazole (20 mg/12 h) and amoxycilline (1 g/12 h) for 5 days, followed by 5 days of omeprazole (20 mg/12 h), clarithromycin (500 mg/12 h) and metronidazole (500 mg/12 h)[170 patients (50.3%)] or concomitant treatment; same drugs at the same doses taken concomitantly for 10 days [168 patients (49.7%)]. Eradication was confirmed with 13C-urea breath test or histology (depending on the indication), at least 4 weeks after treatment. Treatment related adverse events and adherence to treatment were also carefully evaluated. A total of 302 patients completed the follow up and were tested for H. pylori eradication. The success rate of either regimen was defined as the primary outcome measure and was expressed both by intention-to-treat and per protocol. Secondary outcomes included the rate of treatment-emergent adverse events (AE’s) and patients’ adherence to treatment. Concomitant and sequential eradication rates were respectively, 87% versus 81% by intention-to-treat (P=0.15) and 91% versus 86% (P=0.13%) per protocol. Multivariate analysis showed an odds ratio of 1.5 towards better eradication rate with concomitant regimen of borderline significance (OR 1.5, 95% CI 0.9-2.8). Respective adherences to treatment were satisfactory and comparable between treatments (83% versus 82%). AE’s were reported by as many as 59% of their patients but were mostly mild (60%), leading to treatment discontinuation in only 12 patients. In conclusion, the concomitant regimen had a non-significant advantage over sequential therapy and was the only one overcoming the 90% cure rate, per protocol. Both therapies were well tolerated and safe.