Seven-day proton pump inhibitor, amoxicillin and clarithromycin triple therapy. factors that influence Helicobacter pylori eradications success.

AIM: To evaluate which factors influence eradication success with standard triple therapy for Helicobacter pylori. PATIENTS AND METHODS: A prospective study was made of 891 patients infected by H. pylori and diagnosed with duodenal ulcer (n=422), gastric ulcer (n=221), or functional dyspepsia (n=248). Initially, an endoscopy with biopsies of antrum and body (haematoxylin-eosin stain), and a 13C-urea breath test were performed. All patients were treated for seven days with either omeprazole 20 mg twice daily in 442 patients (OCA) or pantoprazole 40 mg twice daily in 449 patients (PCA), associated to clarithromycin (500 mg twice a day) and amoxicillin (1 g twice a day). Two months after completing therapy urea breath test was repeated to confirm eradication. RESULTS: Mean age +/- SD was 51.6 +/- 15 years, 61% were male. Overall eradication rate was 73.7% (95% CI 69-77%) and 80.8% (77-84%) with OCA and PCA therapy, respectively, showing significant difference between treatment regimens (chi 2 =6.3; p= 0.01). As refers to underlying diseases, H. pylori eradication was achieved in 77.4% (74-80%) of peptic ulcers and 77% (71-82%) of functional dyspepsia (p=n.s.). With our two treatment regimens (OCA/PCA) eradication success was 74/81% in peptic ulcer (p=0.03), and 72/80% in functional dyspepsia (p=0.1). In the multivariate analysis, type of therapy was the only variable that correlated with eradication success (odds ratio 1.5; 95% CI: 1.1-2.1) (chi2 model: 6,4; p=0.01). CONCLUSIONS: Standard triple therapy containing a proton pump inhibitor, clarithromycin and amoxicillin for seven days achieves in our community a moderate eradication success; this result could improve by using pantoprazole instead of omeprazole. This therapy is equally effective in patients with peptic ulcer and functional dyspepsia.     

Efficacy of a triple therapy with rabeprazole, amoxicillin, and faropenem as second-line treatment after failure of initial Helicobacter pylori eradication therapy

BACKGROUND/AIMS: Triple therapy consisting of lansoprazole, amoxicillin, and clarithromycin (LAC regimen) is widely used to eradicate Helicobacter pylori in Japan. However, the need for appropriate treatment after failure of initial therapy to eradicate H. pylori has been increasing. We therefore assessed the efficacy of a combination of rabeprazole, amoxicillin, and faropenem for second-line eradication therapy. METHODOLOGY: The subjects were 116 patients positive for H. pylori infection. Patients initially received lansoprazole 60 mg/day, amoxicillin 1500 mg/day and clarithromycin 400 mg/day in two divided doses for 7 days. Patients in whom eradication treatment failed were given rabeprazole 20 mg/day and amoxicillin 1500 mg/day in two divided doses, and faropenem 600 mg/day in three divided doses (RAF regimen) for 7 consecutive days. H. pylori status was assessed by the 13C-urea breath test combined with rapid urease test or H. pylori culture method 8 weeks after completion of therapy. Susceptibility to clarithromycin was determined by the agar dilution method, and genetic polymorphism of CYP2C19 was analyzed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The initial H. pylori eradication rate with the LAC regimen was 76.4% (84/110). Assessment of the CYP2C19 genotypes of the patients in whom eradication therapy failed revealed that homozygous extensive metabolizers accounted for 70.0% (16/23) and heterozygous extensive metabolizers for 30.0% (7/23), with no poor metabolizers. The acquired resistance rate for clarithromycin was 52.0% (12/23). The success rate of re-eradication with the RAF regimen was 91.3% (21/23) with no serious adverse effects. CONCLUSIONS: Triple therapy comprising rabeprazole, amoxicillin, and faropenem is effective for second-line eradication treatment of H. pylori infection, regardless of the genetic polymorphism of CYP2C19 or the presence of resistance to clarithromycin.     

利福布丁三联疗法治疗幽门螺旋杆菌感染文献摘要

目前，以质子泵抑制剂＋克拉霉素＋阿莫西林或甲硝唑三联疗法作为一线方案治疗幽门螺旋杆菌感染有效率接近80％，但是还有相当一部分患者对后者无反应；以质子泵抑制剂＋枸橼酸铋＋四环素＋甲硝唑四联疗法是最常用的二线治疗方案，HP根除率达57％～95％。但是由于四联疗法用药复杂，且不良反应发生率较高，因此须寻找更为有效的、用药方便和耐受性更好的替代治疗方案。     

Efficacy of rifabutin-based triple therapy as second-line treatment to eradicate helicobacter pylori infection

Background

Rifabutin has been found to be effective in multi-resistant patients after various treatment cycles for Helicobacter pylori (HP) infection, but it has not been analysed as a second-line treatment. Therefore, we seek to compare the effectiveness of a treatment regimen including rifabutin versus conventional quadruple therapy (QT).

Methods

Open clinical trial, randomised and multi-centre, of two treatment protocols: A) Conventional regime -QT- (omeprazole 20 mg bid, bismuth citrate 120 mg qid, tetracycline 500 mg qid and metronidazole 500 mg tid); B) Experimental one -OAR- (omeprazole 20 mg bid, amoxicillin 1 gr bid, and rifabutin 150 mg bid), both taken orally for 7 days, in patients with HP infection for whom first-line treatment had failed. Eradication was determined by Urea Breath Test (UBT). Safety was determined by the adverse events.

Results

99 patients were randomised, QT, n = 54; OAR, n = 45. The two groups were homogeneous. In 8 cases, treatment was suspended (6 in QT and 2 in OAR). The eradication achieved, analysed by ITT, was for QT, 38 cases (70.4%), and for OAR, 20 cases (44.4%); p = 0.009, OR = 1.58. Of the cases analysed PP, QT were 77.1%; OAR, 46.5%; p = 0.002. Adverse effects were described in 64% of the QT patients and in 44% of the OAR patients (p = 0.04).

Conclusion

A 7-day rifabutin-based triple therapy associated to amoxicillin and omeprazole at standard dose was not found to be effective as a second-line rescue therapy. The problem with quadruple therapy lies in the adverse side effects it provokes. We believe the search should continue for alternatives that are more comfortably administered and that are at least as effective, but with fewer adverse side effects.

Trial Registration

Current Controlled Trials ISRCTN81058036     

High-dose versus low-dose clarithromycin in 1-week triple therapy, including rabeprazole and levofloxacin, for Helicobacter pylori eradication

GOALS: To compare high-dose versus low-dose clarithromycin in 1-week triple therapy including rabeprazole and levofloxacin. BACKGROUND: Regimens containing rabeprazole and levofloxacin have proved to be effective against H. pylori infection. STUDY: One-hundred H. pylori-positive patients were randomly assigned to one of the following 1-week regimens: rabeprazole 20 mg o.d. plus levofloxacin 500 mg o.d. and clarithromycin 250 mg b.d. (RLC-1 group); rabeprazole 20 mg o.d. plus levofloxacin 500 mg o.d. and clarithromycin 500 mg b.d. (RLC-2 group). H. pylori status was assessed at entry and after the treatment. Patients who experienced treatment failure underwent antibiotic susceptibility testing. RESULTS: Forty-two patients in RLC-1 group (both PP and ITT analysis: 84%; 95%CI: 71-93%) and 47 in RLC2 group (both PP and ITT analysis: 94%; 95% CI: 83-98%) became H. pylori negative. Clarithromycin resistance was detected in all of 8 (100%) RLC-1 failures and in 1 out of 3 (33%) RLC-2 failures. Side effects occurred in 8% of patients in RLC-1 group and in 12% in RLC-2. CONCLUSIONS: Regimens tested are competitive with other PPI-based treatments. One-week triple therapy containing rabeprazole plus, levofloxacin, and high-dose clarithromycin yielded a higher eradicating rate than the one containing low-dose clarithromycin and may be considered as a first-line therapy option.     

Dual proton pump inhibitor plus amoxicillin as an empiric anti-H. pylori therapy: studies from the United States

Background  

Studies with CYP2C19 slow metabolizers have shown that the combination of a proton pump inhibitor (PPI) plus amoxicillin (dual therapy) can reliably cure more than 90% of Helicobacter pylori infections. Theoretically, the use of a PPI dose that provides equivalent acid suppression with fast metabolizers and slow metabolizers would achieve high cure rates irrespective of the CYP2C19 genotype.     

4-day triple therapy with rabeprazole, amoxicillin and clarithromycin in the eradication of Helicobacter pylori in patients with peptic ulcer disease--A pilot study

BACKGROUND: It is well established that a 7-day triple therapy achieves eradication rates of Helicobacter pylori between 90% and 95%. Due to a lack of highly effective short-term eradication studies the aim of the present pilot study was to investigate the effect of a 4-day triple therapy with the new proton pump inhibitor rabeprazole (20 mg b. i. d.) in combination with clarithromycin (500 mg b. i. d.) and amoxicillin (1 g b. i. d.) without acid-suppressive pre-treatment in patients with H. pylori-related peptic ulcer disease. METHODS: 20 patients (11 men, 9 women) with endoscopically diagnosed peptic ulcers (gastric ulcer: n = 5; duodenal ulcer: n = 9; combined gastric and duodenal ulcer: n = 2, gastric or duodenal ulcer scars: n = 4) and H. pylori infection were consecutively recruited. The Helicobacter pylori status was assessed by means of histology, CLO (urea-) test and C13-urea breath test (C13-UBT) at entry. Treatment success was determined by C13-UBT 35-42 days after end of treatment. RESULTS: In 18 out of the 20 patients (90%) [77-100%, 95%-CI] a negative test result was found in C13-UBT 35-42 days after treatment. The 2 patients who remained H. pylori-positive had a duodenal ulcer. CONCLUSION: A 4-day triple therapy of rabeprazole in combination with clarithromycin and amoxicillin seems to be highly effective in eradicating H. pylori and well tolerated in patients with gastric and duodenal ulcer disease. The achieved eradication rate of 90% is comparable with the established 7-day triple therapy regimens. On the basis of these results and considering costs, side effects and compliance a large number of patients should be enrolled in a confirmatory 4-day eradication trial.     

Low-dose rabeprazole, amoxicillin and metronidazole triple therapy for the treatment of Helicobacter pylori infection in Chinese patients

BACKGROUND: Rabeprazole in combination with amoxicillin and metronidazole (RAM) has been shown to be an effective second-line treatment of Helicobacter pylori infection. The effects were compared of 7-day low-dose and high dose rabeprazole in RAM for the primary treatment of H. pylori infection in Chinese patients. METHODS: Helicobacter pylori-positive dyspeptic patients were randomized to receive either (i) rabeprazole 10 mg, amoxicillin 1000 mg and metronidazole 400 mg (RAM-10) or (ii) high-dose rabeprazole 20 mg, amoxicillin 1000 mg and metronidazole 400 mg (RAM-20), each given twice daily for 7 days. Helicobacter pylori eradication was confirmed by (13)c-urea breath test 5 weeks after stopping medications. side-effects of treatments were documented. RESULTS: A total of 120 patients were eligible for analysis. By intention-to-treat and per-protocol analysis, the eradication rates were 83% and 86% in the RAM-10 group and 75% and 76% in the RAM-20 group, respectively (P = 0.26 and P = 0.17). Both regimens were well-tolerated and compliance was >98% in both groups. CONCLUSIONS: Low-dose rabeprazole in combination with amoxicillin and metronidazole is an effective, economical and well-tolerated therapy for the treatment of H. pylori infection in Chinese population.     

A randomized trial comparing seven-day ranitidine bismuth citrate and clarithromycin dual therapy to seven-day omeprazole, clarithromycin and amoxicillin triple therapy for the eradication of Helicobacter pylori.

OBJECTIVE: To assess Helicobacter pylori eradication after one week dual ranitidine bismuth citrate-clarithromycin (RBC-C) or triple omeprazole, clarithromycin and amoxicillin (OCA) therapy. METHODS: In this multicentre Canadian trial, H pylori-positive patients with functional dyspepsia or inactive peptic ulcer disease were randomized to open-label treatment with RBC-C (ranitidine bismuth citrate 400 mg plus clarithromycin 500 mg) or OCA (omezaprole 20 mg, clarithromycin 500 mg and amoxicillin 1000 mg), given twice a day for seven days. Treatment allocation was randomly assigned. H pylori infection was confirmed by positive 13C-urea breath test (13C-UBT). H pylori status was reassessed by UBT at least four and 12 weeks after treatment (negative: d13CO2 below 3.5 per mil). Intention-to-treat (ITT) eradication rates were determined for all patients with confirmed H pylori infection. Per protocol (PP) rate was determined for all patients treated with at least two evaluable follow-up visits. RESULTS: Three hundred five patients were included in the ITT and 222 in the PP analysis. The ITT eradication rates were 66% for RBC-C and 78% for OCA. The PP success rates were 84% for RBC-C and 96% for OCA. The difference for both ITT 12% (95% CI 2 to 22) and PP 12% (95% CI 4 to 19) were statistically significant, P=0.030 and P=0.007, respectively. Treatment was generally well tolerated. CONCLUSION: The eradication rate for the seven-day dual RBC-C regimen was lower than that for OCA.     

Levofloxacin based triple therapy as a second-line treatment after failure of Helicobacter pylori eradication with standard triple therapy

BACKGROUND: Successful eradication of Helicobacter pylori infection after failure of standard triple therapy is difficult. The efficacy and safety of levofloxacin based triple therapy as a first-line therapy has-been studied. AIMS: The aim was to evaluate the efficacy and tolerability of levofloxacin based therapy after a failed standard triple therapy. PATIENTS: We conducted a prospective, uncontrolled study of a consecutive series of 33 patients who failed eradication with 1 week of lansoprazole-amoxicillin-clarithromycin triple therapy. METHODS: The subjects were retreated with 1 week of LA-LVFX triple therapy (lansoprazole, 30 mg twice daily; amoxicillin, 1000 mg twice daily: levofloxacin, 200 mg twice daily). Cure of infection was defined as negative results from culture, histology and a urea breath test 4 to 8 weeks after the second-line therapy. RESULTS: The eradication rate was 69.7% (23/33) by both intention-to-treat and per-protocol analyses (95% confidence interval=61-79%). Seven (21.2%) patients experienced mild side-effects, such as soft stools and taste disturbance. No patient stopped the medication on account of adverse effects. CONCLUSIONS: Levofloxacin based triple therapy is an effective second-line treatment after a failed standard triple therapy.     

Dual therapy using a double dose of lansoprazole with amoxicillin versus triple therapy using a double dose of lansoprazole, amoxicillin, and clarithromycin to eradicate Helicobacter pylori infection: results of a prospective randomized open study

Objectives: The eradication of Helicobacter pylori is recommended in duodenal ulcer disease. The aim of this randomized open trial was to evaluate and compare H. pylori eradication and safety after a dual therapy consisting of lansoprazole (30 mg b.i.d .) and amoxicillin (1 g b.i.d .) versus a triple therapy consisting of lansoprazole (30 mg b.i.d .), amoxicillin (1 g b.i.d .), and clarithromycin (500 mg b.i.d .) administered from day 1 to day 14.
Methods: All patients with an ulcer received lansoprazole (30 mg) from day 15 to day 28. H. pylori status was determined from antral biopsies using histology, culture, and polymerase chain reaction (PCR) upon inclusion and 1–3 months after the end of the treatment.
Results: Of the 50 patients included in the study, five did not adhere to the protocol. H. pylori eradication was obtained in 37.5% of the patients receiving lansoprazole-amoxicillin ( n = 9 /24) and in 95.2% of the patients receiving lansoprazole-amoxicillin-clarithromycin ( n = 20 /21, p < 0.0002 ). Minor side effects appeared in 8.3% of the cases during dual therapy ( n = 2 /24) and in 52% during triple therapy ( n = 13 /22, p < 0.001 ). These side effects consisted mainly of diarrhea and a metallic taste.
Conclusion: Concommitant administration of double doses of lansoprazole with amoxicillin and clarithromycin is very efficacious against H. pylori infection compared with dual therapy.     

Efficacy of quadruple therapy for Helicobacter pylori eradication after failure of proton pump inhibitor‐based triple therapy in Singapore

BACKGROUND: Helicobacter pylori eradication is the mainstay in the treatment of H. pylori‐associated peptic ulcer disease. Current standard eradication therapy consists of 1 week of treatment with a proton pump inhibitor (PPI) and two antibiotics selected from amoxicillin, metronidazole and clarithromycin. In this study we aimed to assess the efficacy of quadruple therapy consisting of a PPI, bismuth, tetra‐cycline and metronidazole in patients for whom initial H. pylori eradication using a triple therapy regimen consisting of a PPI, amoxicillin and clarithromycin was unsuccessful. METHODS: Consecutive patients with H. pylori‐associated peptic ulcer disease, in whom H. pylori with triple therapy had been unsuccessful, were included in the study. These patients had been treated with a regimen that included a PPI (standard dose twice daily), amoxicillin (1 g twice daily) and clarithro­mycin (500 mg twice daily) for 1 week during 1997?2001. Diagnosis of peptic ulcer disease was made at esophagogastroduodenoscopy. Helicobacter pylori infection was considered to be present on the basis of either a positive rapid urease test, positive histo­logical identification of H. pylori or both. Failure of initial H. pylori eradication was established with either a rapid urease test, a ¹³C urea breath test or histology. Quadruple therapy consisted of a PPI (standard dose twice daily), metronidazole (400 mg three times daily), tetracycline (500 mg four times daily) and bismuth subcitrate (240 mg twice daily). Failure of quadruple therapy was diagnosed on the basis of a positive ¹³C urea breath test. RESULTS: Fifty‐three patients received quadruple therapy. The median age was 52 years (range 20?74) and the male to female ratio was 42 : 11. On an intent‐to‐treat basis, the eradication rate was 69.8%, whereas on a per‐protocol basis, the eradication rate was 82.2%. CONCLUSION: We conclude that a 1‐week quadruple therapy regime consisting of a PPI, bismuth, tetracycline and metronidazole was effective in 82.2% of patients who experienced an unsuccessful initial H. pylori eradication attempt with PPI, amoxicillin and clarithromycin.     

Effects of CYP2C19 gene polymorphism on cure rates for Helicobacter pylori infection by triple therapy with proton pump inhibitor (omeprazole or rabeprazole), amoxycillin and clarithromycin in Japan

BACKGROUND: Omeprazole is mainly metabolized by cytochrome P450 2C19 (CYP2C19) in the liver. Rabeprazole, on the other hand, is mainly metabolized to thioether-rabeprazole via a non-enzymatic pathway and partially metabolized to demethylated-rabeprazole by CYP2C19 in liver CYP2C19 status may affect cure rate for Helicobacter pylori infection with proton pump inhibitor triple therapy. AIM: To investigate whether genetic polymorphism of CYP2C19 and selected proton pump inhibitors (omeprazole or rabeprazole) were associated with cure rate for Helicobacter pylori infection using triple therapy with omeprazole or rabeprazole, amoxicillin, and clarithromycin. METHODS: A total of 170 Helicobacter pylori-positive patients with chronic gastritis were randomized to receive one of the following Helicobacter pylori eradication regimens; OAC (omeprazole 20 mg bd, amoxycillin 750 mg bd and clarithromycin 400 mg bd for 1 week) and RAC (rabeprazole 20 mg bd, amoxycillin 750 mg bd and clarithromycin 400 mg bd for 1 week). The CYP2C19 genotype; wild-type or two mutant genes (ml in exon 5 and m2 in exon 4), or both, were identified by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: In DAC regimen, cure rate (per protocol analysis) was 73.3% in homozygous extensive metabolizers, 86.1% in heterozygous extensive metabolizers, and 85.0% in poor metabolizers. In RAC regimen, the cure rate was 81.0% in homozygous extensive metabolizers, 82.9% in heterozygous extensive metabolizers, and 87.5% in poor metabolizers. Cure rate was not significantly different between the CYP2C19 genotypes in both regimens. CONCLUSION: Triple therapy with proton pump inhibitor (omeprazole or rabeprazole), amoxycillin, and clarithromycin is sufficiently effective in cure of Helicobacter pylori infection regardless of CYP2C19 status.