Indian J Gastroenterol DOI 10.1007/s12664-015-0535-x
ORIGINAL ARTICLE
Ciprofloxacin-containing versus clarithromycin-containing sequential therapy for Helicobacter pylori eradication: A randomized trial Nabil Ben Chaabane & Hamad Saadoon Al-Adhba
Received: 20 October 2014 / Accepted: 4 January 2015 # Indian Society of Gastroenterology 2015
Abstract Background and Study Aims Helicobacter pylori eradication rates with standard triple therapy have declined to unacceptable levels. This randomized trial aimed at evaluating the efficacy of a ciprofloxacin containing sequential regimen in the eradication of H. pylori-infected patients vs. a clarithromycin containing sequential therapy. Methods A total of 212 patients were randomized into 14-day therapeutic schemes (106 patients per group): (1) clarithromycin-containing sequential therapy rabeprazole plus amoxicillin for 7 days, followed by rabeprazole plus clarithromycin plus metronidazole for 7 days, and (2) ciprofloxacin-containing sequential therapy using ciprofloxacin instead of clarithromycin. Eradication was confirmed by stool H. pylori antigen. Adverse effects and compliance were assessed by a questionnaire. Results Per protocol cure rates were as follows: 87.6 % in the ciprofloxacin-containing sequential therapy and 76 % in the clarithromycin group. Intention-to-treat cure rates were as follows: 73.5 % for the ciprofloxacin group and 66 % for the clarithromycin group. No differences in compliance or adverse effects were demonstrated among treatments. Conclusion Ciprofloxacin-containing sequential therapy is more effective and equally safe compared to a clarithromycincontaining sequential therapy.
Keywords Quinolones . Sequential therapy . Triple therapy
N. B. Chaabane (*) : H. S. Al-Adhba Hepatogastroenterology Clinic, Qatar Armed Forces, Dohar, Qatar e-mail: [email protected]
Introduction Helicobacter pylori (H. pylori) infection is found in at least 80 % of people in developing countries and 30 % to 40 % of people in developed countries [1]. The infection is known to play a cardinal role in gastritis, peptic ulcer, and gastric cancer [2, 3]. Numerous regimens have been suggested for H. pylori eradication in order to attain more effective eradication resistance. The most frequently used treatment for H. pylori eradication is triple or standard therapy, which includes a combination of two antibiotics (amoxicillin plus clarithromycin or metronidazole) along with a proton pump inhibitor (PPI) for at least 7 days [4]. But, this regimen has been described to be losing its efficacy for H. pylori eradication [5]. Cure rate of triple therapy has been demonstrated to be less than 80 % in several meta-analysis studies [6, 7]. This reduced eradication rate has lead to the development and use of other treatment regimen. In an attempt to improve the success of eradication, a novel 10-day sequential regimen, including a PPI and amoxicillin double therapy for 5 days, followed by a PPI, clarithromycin, and tinidazole triple therapy for a further 5 days, was used in a large, multi-center trial and achieved an eradication rate of 97 % in patients with peptic ulcer disease and 91 % in those with nonulcer dyspepsia [7]. Several meta-analysis and controlled studies showed that the eradication rate of this Bnew^ treatment was significantly higher than that of the triple therapy [8–10]. It has been suggested that prolonging the duration of therapy might improve the treatment success [11, 12]. To our knowledge, only one study has used ciprofloxacin in a randomized controlled trial as a part of a H. pylori eradication triple therapy [13]. Outcomes of this regimen were significantly poorer than other regimens. No data are available about the efficacy of ciprofloxacin in a sequential regimen.
Indian J Gastroenterol
For this reason, the present study was performed to evaluate the efficacy of a ciprofloxacin-containing sequential regimen in the eradication of H. pylori-infected patients vs. clarithromycin-containing sequential therapy.
Methods This was a prospective, parallel, open-label, randomized study. We enrolled 212 patients who consulted our medical unit of Qatar Armed Forces with dyspepsia from February 2013 to March 2014. These patients underwent endoscopy and were found to be positive for H. pylori on rapid urease test. Two biopsies (one from antrum and one from fundus) were performed. During the study period, 830 patients with dyspepsia were seen in our clinic. Six hundred eighteen patients were excluded from the study. Criteria for exclusion from the study were as follows: (1) previous treatment with antibiotics within the past 4 weeks, (2) previous surgery of the upper gastrointestinal tract, (3) PPI treatment within previous 2 weeks, (4) severe psychiatric or neurological disease, (5) current pregnancy or lactation, and (5) allergy to any medication. In the center, patients were randomly assigned to one of the following treatments: group A (n=106), a sequential therapy with 20 mg rabeprazole bid, 1000 mg amoxicillin bid, for 7 days, followed by 20 mg rabeprazole bid, 500 mg clarithromycin bid, and 500 mg metronidazole bid, for another 7 days, and group B (n=106), a sequential therapy with 20 mg rabeprazole bid, 1000 mg amoxicillin bid, for 7 days, followed by 20 mg rabeprazole bid, 500 mg ciprofloxacin bid, and 500 mg metronidazole bid, for another 7 days. For each regimen, the PPI was prescribed at 30 min before meals, and all antibiotics were given after meals. Patients were asked to return to assess the compliance and estimate the adverse reactions at the end of the treatment. Among 212 patients, only 182 patients returned to our clinic after the end of treatment. At least 4 weeks after completion of treatment, a stool H. pylori test was performed to determine if H. pylori had been successfully eradicated. In case of persistent symptoms for patients with stool H. pylori antigen negative, gastroscopy with rapid urease test was performed to confirm or invalidate the result of stool H. pylori antigen. Statistical analyses were performed using Statistical Package for the Social Sciences (SPSS 17.0 for Windows). Univariate analysis, with age, gender, endoscopic diagnosis, history of H. pylori treatment, compliance, and medications as variables, was performed using the χ2 test. The H. pylori eradication rate was determined using intention-to-treat (ITT) and per protocol (PP) analyses using the χ2 test. P60 years Gender Male/female
95 % CI
p-value
1.93
1.2–3.75
0.034
1.22 0.89 7.04 1.52 1.2
0.21–4.06 0.4–1.7 4.6–10.7 0.69–1.14 0.7–1.3
0.1 0.46
ORIGINAL ARTICLE
Ciprofloxacin-containing versus clarithromycin-containing sequential therapy for Helicobacter pylori eradication: A randomized trial Nabil Ben Chaabane & Hamad Saadoon Al-Adhba
Received: 20 October 2014 / Accepted: 4 January 2015 # Indian Society of Gastroenterology 2015
Abstract Background and Study Aims Helicobacter pylori eradication rates with standard triple therapy have declined to unacceptable levels. This randomized trial aimed at evaluating the efficacy of a ciprofloxacin containing sequential regimen in the eradication of H. pylori-infected patients vs. a clarithromycin containing sequential therapy. Methods A total of 212 patients were randomized into 14-day therapeutic schemes (106 patients per group): (1) clarithromycin-containing sequential therapy rabeprazole plus amoxicillin for 7 days, followed by rabeprazole plus clarithromycin plus metronidazole for 7 days, and (2) ciprofloxacin-containing sequential therapy using ciprofloxacin instead of clarithromycin. Eradication was confirmed by stool H. pylori antigen. Adverse effects and compliance were assessed by a questionnaire. Results Per protocol cure rates were as follows: 87.6 % in the ciprofloxacin-containing sequential therapy and 76 % in the clarithromycin group. Intention-to-treat cure rates were as follows: 73.5 % for the ciprofloxacin group and 66 % for the clarithromycin group. No differences in compliance or adverse effects were demonstrated among treatments. Conclusion Ciprofloxacin-containing sequential therapy is more effective and equally safe compared to a clarithromycincontaining sequential therapy.
Keywords Quinolones . Sequential therapy . Triple therapy
N. B. Chaabane (*) : H. S. Al-Adhba Hepatogastroenterology Clinic, Qatar Armed Forces, Dohar, Qatar e-mail: [email protected]
Introduction Helicobacter pylori (H. pylori) infection is found in at least 80 % of people in developing countries and 30 % to 40 % of people in developed countries [1]. The infection is known to play a cardinal role in gastritis, peptic ulcer, and gastric cancer [2, 3]. Numerous regimens have been suggested for H. pylori eradication in order to attain more effective eradication resistance. The most frequently used treatment for H. pylori eradication is triple or standard therapy, which includes a combination of two antibiotics (amoxicillin plus clarithromycin or metronidazole) along with a proton pump inhibitor (PPI) for at least 7 days [4]. But, this regimen has been described to be losing its efficacy for H. pylori eradication [5]. Cure rate of triple therapy has been demonstrated to be less than 80 % in several meta-analysis studies [6, 7]. This reduced eradication rate has lead to the development and use of other treatment regimen. In an attempt to improve the success of eradication, a novel 10-day sequential regimen, including a PPI and amoxicillin double therapy for 5 days, followed by a PPI, clarithromycin, and tinidazole triple therapy for a further 5 days, was used in a large, multi-center trial and achieved an eradication rate of 97 % in patients with peptic ulcer disease and 91 % in those with nonulcer dyspepsia [7]. Several meta-analysis and controlled studies showed that the eradication rate of this Bnew^ treatment was significantly higher than that of the triple therapy [8–10]. It has been suggested that prolonging the duration of therapy might improve the treatment success [11, 12]. To our knowledge, only one study has used ciprofloxacin in a randomized controlled trial as a part of a H. pylori eradication triple therapy [13]. Outcomes of this regimen were significantly poorer than other regimens. No data are available about the efficacy of ciprofloxacin in a sequential regimen.
Indian J Gastroenterol
For this reason, the present study was performed to evaluate the efficacy of a ciprofloxacin-containing sequential regimen in the eradication of H. pylori-infected patients vs. clarithromycin-containing sequential therapy.
Methods This was a prospective, parallel, open-label, randomized study. We enrolled 212 patients who consulted our medical unit of Qatar Armed Forces with dyspepsia from February 2013 to March 2014. These patients underwent endoscopy and were found to be positive for H. pylori on rapid urease test. Two biopsies (one from antrum and one from fundus) were performed. During the study period, 830 patients with dyspepsia were seen in our clinic. Six hundred eighteen patients were excluded from the study. Criteria for exclusion from the study were as follows: (1) previous treatment with antibiotics within the past 4 weeks, (2) previous surgery of the upper gastrointestinal tract, (3) PPI treatment within previous 2 weeks, (4) severe psychiatric or neurological disease, (5) current pregnancy or lactation, and (5) allergy to any medication. In the center, patients were randomly assigned to one of the following treatments: group A (n=106), a sequential therapy with 20 mg rabeprazole bid, 1000 mg amoxicillin bid, for 7 days, followed by 20 mg rabeprazole bid, 500 mg clarithromycin bid, and 500 mg metronidazole bid, for another 7 days, and group B (n=106), a sequential therapy with 20 mg rabeprazole bid, 1000 mg amoxicillin bid, for 7 days, followed by 20 mg rabeprazole bid, 500 mg ciprofloxacin bid, and 500 mg metronidazole bid, for another 7 days. For each regimen, the PPI was prescribed at 30 min before meals, and all antibiotics were given after meals. Patients were asked to return to assess the compliance and estimate the adverse reactions at the end of the treatment. Among 212 patients, only 182 patients returned to our clinic after the end of treatment. At least 4 weeks after completion of treatment, a stool H. pylori test was performed to determine if H. pylori had been successfully eradicated. In case of persistent symptoms for patients with stool H. pylori antigen negative, gastroscopy with rapid urease test was performed to confirm or invalidate the result of stool H. pylori antigen. Statistical analyses were performed using Statistical Package for the Social Sciences (SPSS 17.0 for Windows). Univariate analysis, with age, gender, endoscopic diagnosis, history of H. pylori treatment, compliance, and medications as variables, was performed using the χ2 test. The H. pylori eradication rate was determined using intention-to-treat (ITT) and per protocol (PP) analyses using the χ2 test. P60 years Gender Male/female
95 % CI
p-value
1.93
1.2–3.75
0.034
1.22 0.89 7.04 1.52 1.2
0.21–4.06 0.4–1.7 4.6–10.7 0.69–1.14 0.7–1.3
0.1 0.46
