Five-day proton pump inhibitor-based quadruple therapy regimen is more effective than 7-day triple therapy regimen for Helicobacter pylori infection

BACKGROUND: There have been no reports that describe whether 5-day quadruple therapy (rabeprazole + amoxicillin + clarithromycin + metronidazole; RACM) could substitute for standard 7-day triple therapy as a first-line therapy for Helicobacter pylori. PATIENTS AND METHODS: This study was designed as a randomized prospective single centre study. A total of 160 H. pylori-positive patients who had not received therapy were given either a 5-day RACM regimen (n=80, rabeprazole 20 mg b.d., amoxicillin 750 mg b.d., clarithromycin 200 mg b.d. and metronidazole 250 mg b.d.) or a 7-day RAC regimen (n=80, rabeprazole 20 mg b.d., amoxicillin 750 mg b.d. and clarithromycin 200 mg b.d.). Cure of the infection was assessed by a (13)C urea breath test 1 month after the completion of therapy. RESULTS: The eradication rates of the 5-day RACM regimen and the 7-day RAC regimen were 93% (95% CI: 84--97%) and 81% (95% CI: 71--89%) by intention-to-treat analysis, 94% (95% CI: 86--98%) and 83% (95% CI: 73--91%) by all-patients-treated analysis analysis and 95% (95% CI: 87--98%; P < 0.05) and 82% (95% CI: 72--90%) by per protocol analysis, respectively. No serious adverse effect was observed, and 99% of the patients reported complete compliance. CONCLUSIONS: The cure rate of the 5-day RACM regimen was more effective than the 7-day RAC regimen, suggesting that this regimen could be preferable as a first-line therapy for H. pylori infection.     

Review article: Helicobacter pylori "rescue" regimen when proton pump inhibitor-based triple therapies fail

Even with the currently most effective treatment regimens, about 10-20% of patients will fail to obtain eradication of Helicobacter pylori infection. Therefore, in designing a treatment strategy, we should not focus on the results of primary therapy alone, but also on the final (overall) eradication rate. The choice of second-line treatment depends on which treatment was used initially, as re-treatment with the same regimen is not recommended. Therefore, it is not necessary to perform culture after the first eradication failure. Assessment of the sensitivity of H. pylori to antibiotics only after failure of the second treatment is suggested in clinical practice. Different possibilities of empirical treatment have been suggested. After failure of proton pump inhibitor-amoxicillin-clarithromycin, quadruple therapy has generally been used. More recently, replacement of the proton pump inhibitor and the bismuth compound by ranitidine bismuth citrate has also achieved good results. After proton pump inhibitor-amoxicillin-nitroimidazole failure, re-treatment with proton pump inhibitor-amoxicillin-clarithromycin has been proven to be effective. Finally, first-line treatment should not combine clarithromycin and metronidazole in the same regimen, because of the problem of resistance to both antibiotics. Recently, rifabutin-based rescue therapies have been shown to constitute an encouraging strategy for eradication failures, as they are effective against H. pylori strains resistant to antibiotics.     

Helicobacter pylori eradication with proton pump inhibitor-based triple therapies and re-treatment with ranitidine bismuth citrate-based triple therapy

BACKGROUND: It has been suggested that short-term triple therapy comprising a proton pump inhibitor, plus clarithromycin and amoxycillin be used as first choice in treating H. pylori infection, while eradication failure patients should be further treated with a quadruple therapy. Nevertheless, conflicting results have been reported using these treatment regimens in different countries. METHODS: A total of 278 patients with H. pylori infection were randomised to receive one-week triple therapy, comprising clarithromycin 500 mg b.d., amoxycillin 1 g b.d., and either omeprazole 20 mg b.d. (OAC; 90 patients), or pantoprazole 40 mg b.d. (PAC; 95 patients), or lansoprazole 30 mg b.d. (LAC; 93 patients). H. pylori infection at entry, and eradication 4-6 weeks after therapy had ended, were assessed by rapid urease test and histology on biopsies from the antrum and the corpus. When eradication did not occur, patients were given a 2-week treatment comprising ranitidine bismuth citrate 400 mg b.d., tetracycline 500 mg t.d.s. and tinidazole 500 mg b.d. (RBTT). Eradication in these patients was assessed 4-6 weeks after conclusion of treatment by a further endoscopy. RESULTS: Six patients were lost to the follow-up. At the end of the first course of treatment, the overall H. pylori eradication rate was 78% (95% CI: 73-83) and 79% (95% CI: 75-84) at 'intention-to-treat' (ITT) and 'per protocol' (PP) analysis, respectively, without any statistically significant difference between treatment regimens, although a trend for better results with the omeprazole combination was observed. Moreover, H. pylori eradication was achieved in 82% (95% CI: 75-97) (ITT) and 86% (95% CI: 69-94) (PP) of 38 patients re-treated with RBTT regimen. CONCLUSIONS: Our data found that this short-term triple therapy is not a satisfactory treatment (< 80% eradication rate) for H. pylori infection. The 2-week triple therapy used as re-treatment in eradication failure patients yielded more promising results.     

Review article: treatment of Helicobacter pylori infection with ranitidine bismuth citrate- or proton pump inhibitor-based triple therapies

Triple therapy, combining a proton pump inhibitor with clarithromycin (C) and either amoxycillin (A) or a nitro-imidazole (I) is the standard in Helicobacter pylori eradication therapy. Recently, triple therapies based on ranitidine bismuth citrate (RBC) have emerged as an alternative. This review examines the current literature for studies directly comparing proton pump inhibitor- with RBC-based triple therapies. Seventeen studies were identified, of which three have been published as a full paper. Eradication rates in an intention-to-treat analysis ranged from 51 to 98%. No large difference in cure rates between the different regimens was demonstrated, although the RBC-I-C combination was somewhat superior. No definite conclusions could be made about the impact of metronidazole or clarithromycin resistance since only three studies performed a formal resistance analysis. No serious side-effects were reported, and dropout rates were equal for the two regimens. Both RBC- and proton pump inhibitor-based triple therapies are highly effective. If one prefers a imidazole/clarithromycin combination the evidence presented here suggests that RBC should be used instead of a proton pump inhibitor. Larger studies comparing both forms of triple therapy, using proper resistance analysis, are needed before final conclusions can be reached regarding efficacy in the setting of bacterial resistance.     

Randomised clinical trial: the efficacy of a 10-day sequential therapy vs. a 14-day standard proton pump inhibitor-based triple therapy for Helicobacter pylori in Korea

Aliment Pharmacol Ther 2011; 34: 1098–1105

Summary

Background The eradication rates of Helicobacter pylori (H. pylori) using a proton pump inhibitor (PPI)‐based triple therapy have declined due to antibiotic resistance worldwide. Aim To compare the eradication rate of the 10‐day sequential therapy for H. pylori infection with that of the 14‐day standard PPI‐based triple therapy. Methods This was a prospective, randomised, controlled study. A total of 409 patients with H. pylori infection were randomly assigned to receive either the 10‐day sequential therapy regimen, which consisted of pantoprazole (40 mg) plus amoxicillin (1000 mg) twice a day for 5 days, then pantoprazole (40 mg) with clarithromycin (500 mg) and metronidazole (500 mg) twice a day for another five consecutive days or the 14‐day PPI‐based triple therapy regimen, which consisted of pantoprazole (40 mg) with amoxicillin (1000 mg) and clarithromycin (500 mg) twice a day for 14 days. The pre‐ and post‐treatment H. pylori status were assessed by rapid urease test, urea breath test, or histology. Successful eradication was confirmed at least 4 weeks after finishing the treatment. Results In the intention‐to‐treat analysis, the eradication rates of the 10‐day sequential therapy and of the 14‐day PPI‐based triple therapy were 85.9% (176/205) and 75.0% (153/205), respectively (P = 0.006). In the per‐protocol analysis, the eradication rates were 92.6% (175/205) and 85% (153/204), respectively (P = 0.019). There was no statistically significant difference between the two investigated groups regarding the occurrence of adverse event rates (18.9% vs. 13.3%, P = 0.143). Conclusion The 10‐day sequential therapy achieved significantly higher eradication rates than the 14‐day standard PPI‐based triple therapy in Korea.     

Therapeutic impact of CYP2C19 pharmacogenetics on proton pump inhibitor-based eradication therapy for Helicobacter pylori

Current regimens for the eradication of Helicobacter pylori consist of a proton pump inhibitor (PPI) plus one or two antibacterial agents, such as amoxicillin (AMPC), clarithromycin (CAM) or metronidazole (MNZ). PPIs are mainly metabolized by S-mephenytoin 4'-hydroxylase (CYP2C19) in the liver. The polymorphism of CYP2C19 is associated with the pharmacokinetics and pharmacodynamics of PPIs. Eradication rates by PPI-based therapies are also affected by this genotype, as well as bacterial resistance to antibiotics. An individualized treatment strategy based on CYP2C19-related pharmacogenetics or pharmacogenomics and bacterial resistance is expected to increase the cure rate of the initial treatment. It is also necessary to recognize that there is a possible drug-drug interaction between some of the drugs used in this treatment regimen.     

Meta-analysis: high-dose proton pump inhibitors vs. standard dose in triple therapy for Helicobacter pylori eradication

Background The evidence on whether high‐dose proton pump inhibitors (PPIs) increase cure rates of Helicobacter pylori treatment has not been previously assessed. Aim To evaluate the evidence on the usefulness of high‐dose PPI in standard triple therapy by performing a systematic review and a meta‐analysis. Methods A systematic search was performed in multiple databases and in the abstracts submitted to the Digestive Diseases Week, the European Helicobacter Study Group congress and the United European Gastroenterology Week. Randomized trials comparing a standard dose of a PPI with high‐dose PPI both twice a day in triple therapy combining a PPI plus clarithromycin and either amoxicillin or metronidazole were selected. Relative risk (RR) and 95% confidence intervals (95% CIs) for all comparisons were calculated using Review Manager. Results Six studies fulfilled the inclusion criteria. All used triple therapy for 7 days. A mean intention‐to‐treat cure rate of 82% was achieved with high‐dose PPI and one of 74% with standard dose (RR: 1.09; 95% CI: 1.01–1.17). Subgroup analysis showed that the maximum increase was observed when the PPI compared were omeprazole 20 mg or pantoprazole 40 mg vs. esomeprazole 40 mg. Conclusion High‐dose PPI seems more effective than standard‐dose for curing H. pylori infection in 7‐day triple therapy.     

埃索美拉唑为基础的三联一线治疗幽门螺杆菌的疗效

目的 观察埃索美拉哗联合左氧氟沙星和阿莫西林一线治疗幽门螺杆菌的疗效.方法 163例幽门螺杆菌阳性患者,随机分为3组,分别应用埃索美拉唑20mg每13 2次(A组),埃索美拉唑40 mg每13 2次(B组),埃索美拉唑40 mg每日1次(C组),3组均加用左氧氟沙星500 mg每日1次和阿莫西林1000 mg每日2次,疗程7 d.并且对幽门螺杆菌根除率分别按意愿治疗(ITT)分析和方案(PP)分析进行评估.结果 A、B、C组各治疗方案的根除率:ITT法为82.98%、87.10%、70.37%;PP法为86.67%、88.52%,73.08%.B组明显高于C组(P<0.05).结论 埃索美拉唑联合左氧氟沙星和阿莫西林一线治疗能显著提高幽门螺杆菌根除率.     

Low- versus high-dose azithromycin triple therapy for Helicobacter pylori infection

Background

We report a clinical trial which evaluated the effectiveness of triple therapy containing low- and high-dose azithromycin to treat Helicobacter pylori infection.

Methods

From March 1997 to March 1998, patients infected with H. pylori were assigned to receive either: Treatment 1: ranitidine bismuth citrate (RBC) (400 mg b.d.) and amoxycillin (1 g b.d.) for 10 days with azithromycin 500 mg o.m. for 3 days; or Treatment 2: RBC and amoxycillin for 10 days with azithromycin 1 g o.m. for 3 days. H. pylori eradication was established by a urea breath test at least 4 weeks after therapy. Side-effects and compliance were assessed using a diary.

Results

Sixty-eight patients were enrolled. Fifty-seven per cent of patients were treated for active peptic ulcer disease or a history of peptic ulcer disease. Treatment 1 cured H. pylori in 44% and 44% by per protocol and intention-to-treat analysis, respectively. The corresponding eradication rates for Treatment 2 were 79% and 75%. Two patients taking Treatment 2 dropped out of the study because of side-effects.

Conclusions

With RBC and amoxycillin for 10 days, azithromycin at a dose of 1 g/day for 3 days was significantly better at curing H. pylori infection than azithromycin 500 mg/day for 3 days.

     

Helicobacter pylori eradication in clinical practice: one-week low-dose triple therapy is preferable to classical bismuth based triple therapy

Background : Both classical 2-week bismuth based triple therapy and the newer 1-week low-dose omeprazole based triple therapies achieve high Helicobacter pylori eradication rates in controlled clinical trials and are in widespread use in routine clinical practice. However, their efficacy and acceptability in this setting is unproved.
Methods : Over a 1-year period, the notes for patients attending a dedicated H. pylori treatment clinic were audited. Assessments were made of patient demographics, diagnosis, smoking habits, use of H₂-antagonists, regimen used, efficacy of treatment, compliance and side-effects experienced.
Results : 223 sets of notes were audited. 89 patients received bismuth, tetracycline and metronidazole for two weeks and 111 patients received omeprazole, clarithromycin and either metronidazole (63 patients) or tinidazole (48 patients) for 1 week. Successful eradication was achieved in 75/89 (84.3%), 56/63 (89%) and 42/48 (88%), respectively, ( P = N.S.). Severe side-effects occurred in 11 (12%) of patients receiving bismuth based treatment compared to 1 (0.9%) patient receiving omeprazole based regimens ( P <0.02). Treatment failure in patients receiving omeprazole based treatment was associated with smoking ( P <0.05).
Conclusions : Outside the context of clinical trials, both regimens achieved acceptable eradication rates. However, 1-week low-dose therapy is preferable due to the lower incidence of severe side-effects.     

四联疗法治疗幽门螺旋杆菌感染的临床体会

目的观察以PPl为基础联合三种抗生素的四联疗法治疗幽门螺杆菌感染的根治效果及安全性。方法治疗组给埃索美拉唑20mg,阿莫西林1g,克拉霉素250mg及左氧氟沙星200mg,每日2次服药,对照组给埃索美拉唑20mg,阿莫西林lg,克拉霉素250mg,每日2次服药。疗程均为1周,治疗期间停用其他药物,疗程结束4周后复诊,观察Hp根除率、症状缓解率及不良反应发生率。结果疗程结束4周后复查Hp根除率治疗组为95．2％,对照组为76．7％,两组比较差异有统计学意义（P〈0．05）;治疗组症状缓解率83．3％,不良反应发生率14．6％,对照组症状缓解率82．6％,不良反应发生率16．7％,无统计学意义（P〉0．05）。结论四联疗法可获得较高Hp根治率,疗程短,不良反应少,值得推广临床治疗。     

Incidence of duodenal ulcer healing after 1 week of proton pump inhibitor triple therapy for eradication of Helicobacter pylori

Background:

A number of clinical studies have assessed the efficacy of short-term twice-daily Helicobacter pylori eradication regimens but few have investigated the proportion of patients in whom duodenal ulcer disease was healed with these regimens.

Aim:

To compare the safety and efficacy of four 1-week H. pylori eradication regimens in the healing of H. pylori associated duodenal ulcer disease.

Methods:

Following endoscopic confirmation of duodenal ulcer disease and a positive CLO test, patients underwent a ¹³C-urea breath test to confirm H. pylori status. Treatment with one of four regimens: LAC, LAM, LCM or OAM, where L is lansoprazole 30 mg b.d., A is amoxycillin 1 g b.d., M is metronidazole 400 mg b.d., C is clarithromycin 250 mg b.d., and O is omeprazole 20 mg b.d., was assigned randomly to those patients who were H. pylori positive, with 62 (LAC), 64 (LAM), 61 (LCM) and 75 (OAM) patients in each treatment group. Follow-up breath tests and endoscopies were performed at least 28 days after the end of treatment.

Results:

Duodenal ulcer disease was healed 28 days after treatment in 53/62 (85.5%) patients who were treated with LAC, 52/64 (81.3%) of patients treated with LAM, 49/61 (80.3%) of patients treated with LCM and 60/75 (80.0%) of patients treated with OAM (intention-to-treat analysis, n=262, assumed unhealed if no follow-up endoscopy was performed). All the treatments were of similar efficacy (P=0.85, chi-squared test) with regard to the healing of duodenal ulcer disease.

Conclusions:

The four 1-week treatment regimens were equally effective in healing H. pylori associated duodenal ulcer disease.

     

Single vs. double dose of a proton pump inhibitor in triple therapy for Helicobacter pylori eradication: a meta-analysis

BACKGROUND: Triple therapies combining a double dose of proton pump inhibitor plus two antibiotics are the standard treatment for Helicobacter pylori infection. Some reports suggest that the use of half the dose of proton pump inhibitor is equally effective. AIM: To compare the efficacy of a single vs. double dose of proton pump inhibitor in triple therapy. METHODS: We conducted a MEDLINE search. The search strategy included the words (pylori) AND (triple, PPI, proton pump, omeprazole, rabeprazole, pantoprazole, lansoprazole, clarithromycin, amoxicillin, amoxycillin or metronidazole). Abstracts of the articles obtained and papers presented at the European Helicobacter pylori Study Group and American Gastroenterological Association congresses from 1996 to 2001 were examined. Inclusion criteria were: (i) randomized studies with at least two branches of triple therapy including a proton pump inhibitor and two standard antibiotics; (ii) branches could differ only in terms of proton pump inhibitor dosage. A meta-analysis was conducted using conventional shareware (Review Manager 4.1). RESULTS: Thirteen studies met the inclusion criteria with a total of 2391 patients. Cure rates with double doses of proton pump inhibitor were higher in both the intention-to-treat analysis (83.9% vs. 77.7%; Peto odds ratio, 1.51; 95% confidence interval, 1.23-1.85; P < 0.01) and per protocol analysis (89% vs. 81%; Peto odds ratio, 1.96; 95% confidence interval, 1.55-2.47; P < 0.01). CONCLUSION: Triple therapies containing a single dose of proton pump inhibitor are less effective than those containing a standard double dose of proton pump inhibitor.     

锌剂三联疗法治疗Hp相关性十二指肠溃疡

目的观察锌剂三联疗法治疗幽门螺杆菌(Hp)相关性十二指肠溃疡疗效。方法87例患者随机分为两组。锌剂组(45例):醋氨己酸锌300mg熏2次/d熏法莫替丁20mg熏2次/d熏阿莫西林500mg熏2次/d鸦铋剂组(42例):得诺240mg熏2次/d熏法莫替丁20mg熏2次/d熏阿莫西林500mg熏2次/d。疗程均为4周。疗程结束1周后胃镜检查。结果锌剂组的Hp根除率和溃疡愈合率分别为86.87%和91.11%,铋剂组分别为88.10%和90.48%,两者比较无显著性差异(P>0.05),但平均不良反应积分铋剂组为4.36,锌剂组为2.37,两者比较有显著性差异(P<0.05)。结论两种疗法治疗Hp相关性十二指肠溃疡疗效相当,但是铋剂组不良反应发生率较高。