Downloaded from www.microbiologyresearch.org by IP: 54.167.64.178 On: Mon, 18 Jul 2016 06:04:20 Sequential, concomitant and hybrid first-line therapies for Helicobacter pylori eradication: a prospective randomized study Vincenzo De Francesco, 1 Cesare Hassan, 2 Lorenzo Ridola, 2 Floriana Giorgio, 3 Enzo Ierardi 3 and Angelo Zullo 2 Correspondence Vincenzo De Francesco vdefrancesco@alice.it Received 2 January 2014 Accepted 27 February 2014 1 Section of Gastroenterology, Department of Medical Sciences, University of Foggia, Ospedali Riuniti, Foggia, Italy 2 Gastroenterology and Digestive Endoscopy, ‘Nuovo Regina Margherita’ Hospital, Rome, Italy 3 Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Italy Helicobacter pylori eradication remains a challenge for physicians. Sequential, concomitant and the hybrid regimens have been proposed as novel, more effective therapies. We compare the efficacy of these therapies. Dyspeptic patients referred for upper endoscopy with H. pylori infection were enrolled. Patients were randomized to receive: (a) sequential therapy – 20 mg omeprazole and 1 g amoxicillin for 5 days, followed by 20 mg omeprazole, 500 mg clarithromycin and 500 mg tinidazole for the successive 5 days; (b) concomitant therapy – 20 mg omeprazole, 1 g amoxicillin, 500 mg clarithromycin and 500 mg tinidazole for either 5 days (5 day concomitant) or 14 days (14 day concomitant); or (c) hybrid therapy – 20 mg omeprazole and 1 g amoxicillin for 7 days, followed by 20 mg omeprazole, 1 g amoxicillin, 500 mg clarithromycin and 500 mg tinidazole for the successive 7 days. All drugs were given twice daily. Bacterial eradication was checked by using a [ 13 C]urea breath test. In ‘intention-to-treat’ analysis, sequential therapy achieved the highest eradication rate, which was higher than that of 5 day concomitant therapy (90 vs 78.1 %; P50.02). The success rate did not statistically differ among the sequential and either 14 day concomitant (90 vs 86.3 %; P5not significant) or hybrid therapies (90 vs 82.7 %; P5not significant). The 10 day sequential, 14 day concomitant and 14 day hybrid therapies, but not the 5 day concomitant regimen, achieved similarly high eradication rates. The lower therapeutic cost coupled with the lower number of tablets needed would favour the sequential therapy as the first-line H. pylori treatment in clinical practice. INTRODUCTION The Helicobacter pylori eradication rate following standard 7 day triple therapies has decreased in different countries (Graham & Fischbach, 2010; Gisbert & Calvet, 2011; McNicholl & Gisbert, 2012), and attempts to improve the efficacy by prolonging treatment duration to 10–14 days showed a small benefit (Fuccio et al., 2007). Therefore, novel first-line therapies have been proposed, including the sequential, concomitant and, more recently, hybrid therapy regimens. The standard 10 day sequential therapy, consist- ing of a proton pump inhibitor (PPI) and amoxicillin dual therapy for the first 5 days, followed by a PPI, clarithro- mycin and tinidazole triple therapy for the successive 5 days, was pioneered in Italy in 2000 (Zullo et al., 2000). Several trials showed a high efficacy of this therapy, with a success rate constantly higher than that of standard 7–10 day triple therapies (Zullo et al., 2007). In the last few years, the concomitant regimen first introduced in 1998 (Okada et al., 1998; Treiber et al., 1998) has been revisited for H. pylori eradication. This regimen includes PPI, clarithro- mycin, amoxicillin and metronidazole, i.e. it is a bismuth- free quadruple therapy. However, different durations, widely ranging from only 3 to 14 days, have been proposed for this therapy, so a well-standardized regimen is lacking (Gisbert & Calvet, 2012). Different studies demonstrated a high (.90 %) efficacy of concomitant therapy, even when administered for only 5 days (Treiber et al., 1998, 2002; Nagahara et al., 2000, 2001; Kongchayanun et al., 2012), and in a recent pilot study an 85.5 –91.6 % eradication rate was achieved (Zullo et al., 2013a). However, other studies suggested a longer regimen so that a standard therapy duration is unclear (Essa et al., 2009; Graham & Fischbach, 2010). The 14 day hybrid therapy combines the sequential Abbreviations: CI, confidence interval; ITT, intention to treat; PP, per protocol; PPI, proton pump inhibitor. Journal of Medical Microbiology (2014), 63, 748–752 DOI 10.1099/jmm.0.072322-0 748 072322 G 2014 The Authors Printed in Great Britain