Volume 5 • Number 1 • 2000 HELICOBACTER © Blackwell Science, Inc. 1083-4389/00/$15.00/52 52–56 52 Four-Day, Twice Daily, Quadruple Therapy with Amoxicillin, Clarithromycin, Tinidazole and Omeprazole to Cure Helicobacter pylori Infection: A Pilot Study Xavier Calvet,* Llùcia Titó, † Ricard Comet,* Neus García, ‡ Ralel Campo, § and Enric Brullet § *Medicine and ‡ Surgery Services and § Endoscopy Unit, Corporació Sanitària Parc Taulí, Sabadell; † Medicine Service, ABSTRACT Hospital de l’Esperit Sant, Sta. Coloma Gramanet, Spain Background. The best regimen for the treatment of Helicobacter pylori infection has yet to be defined. Four-day quadruple therapy with tetracycline, metro- nidazole, bismuth, and a proton pump inhibitor has been shown to obtain a very high cure rate. However, the fact that it must be taken four times daily may in- terfere with compliance. The objective of the study was to test the efficacy and tolerability of a new 4-day ther- apy with 4 drugs taken every 12 hours to cure H. pylori infection. Patients and Methods. Fifty-six consecutive patients with peptic ulcer disease and H. pylori infection were treated with an oral 4-day course with omeprazole (20 mg/12 hours), clarithromycin (500 mg/12 hours), amoxicillin (1 g/12 hours) and tinidazole (500 mg/12 hours). Effi- cacy of the treatment was determined at least 2 months after therapy either by biopsy (in the case of gastric ul- cer) or by 13 C-urea breath test. A second breath test was performed at least 6 months after therapy. Results. Two patients were lost to follow-up. Forty-nine of the remaining 54 patients were cured at the first con- trol [intention-to-treat cure rate: 87.5% (CI 95% 75– 94%); per protocol cure rate: 90.7% (CI 95% 81– 98%)]. Forty-three of these 49 cured patients returned for a second 13 C urea breath-test at 6–12 months. Two of them were not cured, giving a long-term cure rate of 85.5% per protocol and 73.2% by intention-to-treat. Compliance was good, although 25 patients had mild side effects. Conclusion. This particular four-day therapy is well tol- erated, easy to follow, and achieves an acceptably high cure rate. T here is currently no ideal treatment for Heli- cobacter pylori infection [1–4]. Recent recom- mendations suggest the use of the combination of a proton pump inhibitor (PPI) and two antibiotics, mainly clarithromycin and either metronidazole or amoxicillin [5]. Initial studies reported eradication rates with these therapies to be over 90% [6]. In addition, large, multicenter, comparative studies [7,8] reporting a 95% eradication rate for 7-day PPI based therapies have been published. How- ever, results of PPI-based triple therapies have been found to be lower in many southern Euro- pean countries [9–11], in recent US multicenter trials (82%) [12] and even in recent pooling data studies [13]. All these analyses suggest that cure rates with PPI-based triple therapies range be- tween 80 and 85%, depending on the antibiotic combination utilized. A potentially useful alternative to triple therapy is the combination of four drugs, the so-called quadruple therapy. Most quadruple therapies con- sist of a combination of omeprazole, metronida- zole, tetracycline and a bismuth salt for one or two weeks [14]. Although recognized as one of the most effective therapies, with eradication rates of over 90% even with four-day schedules [15,16] quadruple therapy is recommended only as a sec- ond line therapy. The inconvenience of its dos- age—two, three and four times daily—and the large number of pills required are the main rea- sons why it is not generally indicated as first line therapy [5]. Attempts to simplify the therapy by using a twice daily schedule have produced disap- pointing results [17]. Against this background, the aim of the present study was to analyze the useful- ness of a new, simplified, quadruple therapy with Reprint requests to: X. Calvet, M.D., Internal Medicine, Department Consorci Hospitalari del Parc Taulí, Parc Taulí s/n, 08208 Sabadell (Barcelona), Spain. E-mail: xcal- vet@cspt.es