One-week triple vs. quadruple therapy for Helicobacter pylori infection - a randomized trial

BACKGROUND: Seven-day triple therapy including omeprazole, clarithromycin and amoxicillin has become the treatment of choice for Helicobacter pylori infection. However, 7 days of classical quadruple therapy combining omeprazole, tetracycline, metronidazole and bismuth may be an alternative to triple therapy. AIM: To compare triple vs. quadruple therapy for H.pylori eradication. METHODS: Three hundred and thirty-nine patients with peptic ulcer and H. pylori infection were included in the study. Patients were randomized to receive omeprazole, 20 mg, amoxicillin, 1 g, and clarithromycin, 500 mg, all b.d., or omeprazole, 20 mg b.d., tetracycline chloride, 500 mg, metronidazole, 500 mg, and bismuth subcitrate, 120 mg, all t.d.s. Cure was defined as a negative urea breath test at least 2 months after treatment. RESULTS: Per protocol and intention-to-treat cure rates were 86%[95% confidence interval (CI), 80-91%] and 77% (95% CI, 70-83%) for triple therapy, and 89% (95% CI, 82-93%) and 83% (95% CI, 76-88%) for quadruple therapy. No significant differences between the groups were found in the cure rates, compliance or side-effects. CONCLUSION: One-week triple and quadruple therapy show similar results when used as first-line eradication treatment.     

Lansoprazole, levofloxacin and amoxicillin triple therapy vs. quadruple therapy as second-line treatment of resistant Helicobacter pylori infection

AIM: To test the efficacy of levofloxacin-based second-line therapy for resistant Helicobacter pylori infection. METHODS: One hundred and six patients who failed H. pylori eradication were randomized to receive (i) lansoprazole 30 mg, amoxicillin 1 g, levofloxacin 500 mg, all given twice daily for 7 days (LAL); or (ii) lansoprazole 30 mg twice daily, metronidazole 400 mg thrice daily, bismuth subcitrate 120 mg and tetracycline 500 mg four times daily for 7 days (quadruple). Post-treatment H. pylori status was determined by (13)C-urea breath test. RESULTS: Intention-to-treat and per-protocol H. pylori eradication rates were 57/60% for the LAL group and 71/76% for the quadruple group respectively. Metronidazole, clarithromycin, amoxicillin and levofloxacin resistance were found in 76%, 71%, 0% and 18% of patients, respectively. Levofloxacin resistance led to treatment failure in the LAL group. For patients with dual resistance to metronidazole and clarithromycin, the eradication rates were 79% in the LAL group (levofloxacin-sensitive) and 65% in the quadruple group (P=0.34). CONCLUSION: Lansoprazole, amoxicillin plus levofloxacin second-line therapy is comparable with quadruple therapy in efficacy. Subjects, especially those with dual resistance to metronidazole and clarithromycin, may consider levofloxacin-based therapy for levofloxacin-sensitive strains.     

Randomized controlled study of rabeprazole,levofloxacin and rifabutin triple therapy vs. quadruple therapy as second-line treatment for Helicobacter pylori infection

AIM: To test the efficacy of rabeprazole, levofloxacin and rifabutin triple therapy vs. quadruple therapy for the second-line treatment of Helicobacter pylori infection. METHODS: One hundred and nine patients who had failed previous H. pylori eradication were randomized to receive: (i) rabeprazole, 20 mg b.d., rifabutin, 300 mg once daily, and levofloxacin, 500 mg once daily, for 7 days (triple therapy); or (ii) rabeprazole, 20 mg b.d., metronidazole, 400 mg t.d.s., bismuth subcitrate, 120 mg q.d.s., and tetracycline, 500 mg q.d.s., for 7 days (quadruple therapy). Endoscopy and culture were performed before treatment. RESULTS: The clarithromycin (79% vs. 21%, P < 0.001) and metronidazole (89% vs. 40%, P < 0.001) resistance rates were significantly higher in patients with previous exposure than in those with no previous exposure. The intention-to-treat and per protocol eradication rates were 91%/91% for the triple therapy group and 91%/92% for the quadruple therapy group. For patients with double resistance to metronidazole and clarithromycin, the eradication rates were 85% (17/20) in the triple therapy group and 87% (13/15) in the quadruple therapy group. Compliance was greater than 95% for both regimens. CONCLUSION: Rabeprazole, levofloxacin and rifabutin-based triple therapy and quadruple therapy were equally effective as second-line treatments for H. pylori infection.     

Triple vs. quadruple therapy for treating Helicobacter pylori infection: a meta-analysis

BACKGROUND: Triple therapy (proton pump inhibitor, clarithromycin and amoxicillin or an imidazole) is the first-line treatment for Helicobacter pylori infection. However, the effectiveness of triple therapy is decreasing due to the increase in antibiotic resistance. Quadruple therapy (proton pump inhibitor, tetracycline, metronidazole and a bismuth salt) is a very effective regimen even in areas of high prevalence of antibiotic resistance, and may be an alternative first-line treatment. AIM: To compare triple vs. quadruple therapy for the first-line treatment of H. pylori infection. METHODS: An extensive literature search was performed to identify randomized trials comparing triple vs. quadruple therapy. Selected trials were included in a meta-analysis using Review Manager 4.1. RESULTS: Four studies met the inclusion criteria. Eradication rates with quadruple therapy were slightly higher in both the intention-to-treat (81% vs. 78%; odds ratio, 0.83; 95% confidence interval, 0.61-1.14) and per protocol (88% vs. 85%; odds ratio, 0.81; 95% confidence interval, 0.55-1.20) analysis, although the differences were not statistically significant. Nor were there significant differences in compliance or adverse effects between the therapies. CONCLUSION: Triple and quadruple therapies seem to be roughly equivalent in terms of effectiveness, compliance and side-effects profile when administered as first-line treatment for H. pylori infection.     

含利福布汀的三联或四联疗法在幽门螺杆菌根除失败后的应用

根除幽门螺杆菌(Hp)是防治消化性溃疡、慢性活动性胃炎等疾病的主要措施,作为一线治疗的三联或四联方案的根除率逐年降低。抗分枝杆菌药物利福布汀有较强的抗Hp活性,国内外陆续有将含利福布汀方案作为Hp感染一线治疗失败后的补救或三/四线方案的报道。本文对利福布汀的作用机制、药动学特点及含利福布汀方案的疗效和安全性作一综述。     

Two-week dual vs. one-week triple therapy for cure of Helicobacter pylori infection in primary care: a multicentre, randomized trial

BACKGROUND: One-week triple therapy has been suggested to be superior to two-week omeprazole-clarithromycin therapy for the cure of Helicobacter pylori infection. However, direct comparisons of the two treatments are scarce. AIM: To compare triple with dual therapy for H. pylori infection in the primary care setting. METHODS: One hundred and forty-five patients with duodenal ulcer and H. pylori infection were randomized to receive omeprazole 20 mg b.d. and clarithromycin 500 mg t.d.s. for 14 days (OC14 group, 69 patients) or omeprazole 20 mg b.d., clarithromycin 500 mg b.d. and amoxycillin 1 g b.d. for 7 days (OCA7 group, 76 patients). Eradication was evaluated by the 13C-urea breath-test. RESULTS: Intention-to-treat analysis showed a cure rate of 48% (95% CI: 36-60%) in the OC14 group, and 71% (95% CI: 59-80%) in the OCA7 group (P=0.0004). Per protocol analysis showed cure rates of 51% (95% CI: 38-63%, 33/65 patients) and 82% (95% CI: 70-90%, 54/66 patients), respectively (P=0.0001). There were no significant differences in compliance or side-effects. CONCLUSION: One-week twice-daily triple therapy is superior to 2-week dual therapy, but the cure rate in primary care was far below 90%.     

Clinical trial: levofloxacin-based quadruple therapy was inferior to traditional quadruple therapy in the treatment of resistant Helicobacter pylori infection

BACKGROUND: The efficacy of levofloxacin-based quadruple therapy in resistant Helicobacter pylori infection is not known. AIM: To test the efficacy of levofloxacin-based quadruple therapy and traditional quadruple therapy in resistant H. pylori infection. METHODS: One hundred and two patients with resistant H. pylori infection were randomized to 1 week of either EBAL (esomeprazole 40 mg b.d., bismuth subcitrate 240 mg b.d., amoxicillin 1 g b.d. and levofloxacin 500 mg b.d.) or EBMT (esomeprazole 40 mg b.d., bismuth subcitrate 240 mg b.d., metronidazole 400 mg t.d.s. and tetracycline 500 mg q.d.s.). (13)C-urea breath test was performed at week 12 to assess post-treatment H. pylori status. RESULTS: In intention-to-treat analysis H. pylori eradication was achieved in 37 of 51 (73%) subjects in EBAL and 45 of 51 (88%) subjects in EBMT groups, respectively (P = 0.046). Per-protocol eradication rates of EBAL and EMBT groups were 78% and 94%, respectively (P = 0.030). The intention-to-treat eradication rate was statistically lower for EBAL than EMBT (56% vs. 90%, P = 0.013) among those who had failed more than one course of eradication therapy. Previous levofloxacin triple therapy did not affect the efficacy of either protocol significantly. CONCLUSIONS: Levofloxacin-based quadruple therapy was inferior to traditional quadruple therapy for resistant H. pylori infection.     

Bismuth-based quadruple therapy for Helicobacter pylori - a single triple capsule plus lansoprazole

BACKGROUND: Recently a new 'all in one' single capsule with the three components of bismuth-based triple therapy became available in trials for treating Helicobacter pylori. AIM: To investigate the efficacy and tolerability of this new capsule when combined with lansoprazole. METHODS: A total of 66 consecutive infected patients from a single centre received two single triple capsules four times daily and lansoprazole 30 mg b.d. for 7 days. Each capsule contained 60 mg of bismuth subcitrate, 125 mg of tetracycline and 125 mg of metronidazole. Endoscopy with biopsies for CLO-test, histology and culture from antrum and corpus was performed before and at least 5 weeks after treatment. RESULTS: The per protocol cure rate was 56/64 (88%, 95% CI: 79-95%); by intention-to-treat 56/65 (86%, 95% CI: 78-95%). The per protocol cure rate in metronidazole sensitive strains was 40/43 (93%, 95% CI: 85-100%); in resistant strains 5/9 (56%, 95% CI: 23-88%). There was one drop-out due to adverse events. CONCLUSIONS: It is possible to combine the components of bismuth-based triple therapy into a single capsule. Based on the results it can be assumed that the capsule releases its content in the stomach. When combined with lansoprazole it reaches high cure rates, especially in metronidazole sensitive strains. This new approach simplifies bismuth-based anti-Helicobacter therapy.     

标准三联疗法四联疗法及序贯疗法根除幽门螺杆菌的疗效观察

目的比较标准三联疗法、四联疗法及序贯疗法根除幽门螺杆菌(Hp)的疗效及安全性。方法300例非溃疡性消化不良者随机入选三联、四联及序贯疗法组,三联疗法组予兰索拉唑+阿莫西林+克拉霉素治疗10d。四联疗法组予兰索拉唑+胶体次枸橼酸铋+阿莫西林+克拉霉素治疗10d。序贯疗法组前5d予兰索拉唑+阿莫西林治疗,后5d予兰索拉唑+克拉霉素+甲硝唑治疗。治疗结束至少停药4周后复查14 C尿素呼气试验,结果阴性表示根除成功。同时评估疗效及安全性。对Hp根除率进行意向性分析和符合方案分析比较。结果意向性分析显示三联疗法组、四联疗法组及序贯疗法组的Hp根除率分别是66%(66/100)、82%(82/100)及84%(84/100)。符合方案分析显示三联疗法组、四联疗法组及序贯疗法组的Hp根除率分别是72%(66/92)、91%(82/90)及89%(84/94)。意向性分析及符合方案分析均表明三联疗法组Hp根除率明显低于四联疗法组或序贯疗法组,差异有统计学意义(P均<0.05),而四联疗法组与序贯疗法组间差异无统计学意义(P>0.05)。结论四联疗法或序贯疗法可作为临床根治Hp的一线治疗方案。     

3联与4联根除治疗幽门螺旋杆菌感染的效果-成本比较

目的比较3联与4联根除法对幽门螺旋杆菌(Hp)感染所产生的治疗效果及成本。方法纳入2016年4~12月我院收治50例幽门螺旋杆菌感染病例为研究对象,按照随机数字表法分为两组,各25例,A组采取4联根除法,B组采取3联根除法,比较两组疼痛消失时间、Hp根除率、成本-效果。结果 A组疼痛消失时间(5.63±1.75)d,明显短于B组(8.18±2.06)d,且Hp根除率为96.00%,明显高于B组72.00%(P<0.05);A组C/E为2.265,小于B组C/E为2.997。结论相对于3联疗法,对Hp感染患者采取4联根除法可快速缓解疼痛症状,获得更加理想的疗效,且减少治疗成本,值得推广。     

秘剂四联疗法与序贯疗法治疗幽门螺杆菌感染的Meta分析

目的 系统评价10天秘剂四联疗法和10天序贯疗法治疗中国患者幽门螺旋杆菌(Hp)感染的疗效和安全性。方法 利用中英文数据库,查找使用两种方案治疗中国患者Hp感染患者的随机对照实验(RCT)。根据纳入排除标准选取研究,提取资料,并使用Jadad量表评价研究质量,采用STATA12统计软件进行Meta分析。结果 纳入14项RCT研究,1518名患者,秘剂四联疗法和序贯疗法的Hp清除率按意向分析(ITT)分别为82.75%和84.13 %(RR = 0.99(0.95,1.04),P=0.658),两种疗法Hp根除率方面的差异无统计学意义。秘剂四联疗法与序贯疗法的不良反应发生率分别是14.19%和12.45 %(RR = 1.30(0.99,1.69),P=0.056),不良反应发生率差异也无统计学意义。结论 当前证据表明,10天铋剂四联疗法和10天序贯疗法治疗中国患者Hp感染的疗效和安全性相当,可以作为中国患者的一线治疗方案。     

Modified seven-day, quadruple therapy as a first line Helicobacter pylori treatment

BACKGROUND: Cure rates of 7-day triple therapy seem to be decreasing. Quadruple therapies may be an alternative, although their complex administration makes patient acceptance difficult. OBJECTIVE: To test the usefulness of a thrice a day, quadruple therapy to cure Helicobacter pylori infection. PATIENTS AND METHODS: A total of 122 consecutive patients with peptic ulcer and Helicobacter pylori infection were treated with omeprazole 20 mg b.d., tetracycline chlorhydrate 500 mg t.d.s., metronidazole 500 mg t.d.s., and bismuth subcitrate 120 mg t.d.s. administered with meals for 7 days. Cure was tested by either endoscopy or breath test after 2 months, and by urea breath test 6 months after therapy. RESULTS: Seven patients were lost to follow-up. Of the remaining 115, 110 were cured at the first control, giving an intention-to-treat cure rate of 90.2% (95% CI: 83-95%) and a per protocol cure rate of 95.7% (95% CI: 90-98%). One hundred three patients returned for a 6-month breath test; all but one were cured. Side-effects were minimal or minor in 47 patients (40.8%) and moderate in four (3.4%). Compliance was good, 95% of patients taking more than 90% of the pills. Six (5%) patients stopped treatment after 1, 2, 4 (two patients) and 6 (two patients) days. CONCLUSION: Thrice a day quadruple therapy shows excellent cure rates, far above 90%, is well-tolerated and compliance is easy. Head-to-head comparison with triple therapies as first line Helicobacter pylori treatment seems warranted.     

Rabeprazole-based 3-day and 7-day triple therapy vs. omeprazole-based 7-day triple therapy for the treatment of Helicobacter pylori infection

BACKGROUND: Rabeprazole is a new proton pump inhibitor with more potent acid suppressive and anti-Helicobacter effects. AIM: To compare two different regimens of rabeprazole-based triple therapy vs. 7-day omeprazole-based triple therapy for the eradication of Helicobacter pylori infection. METHOD: Patients with proven H. pylori infection were randomized to receive: (i) 7-day rabeprazole, 10 mg, amoxicillin, 1000 mg, and clarithromycin, 500 mg, all twice daily; (ii) 3-day rabeprazole, 20 mg, amoxicillin, 1000 mg, and clarithromycin, 500 mg, all twice daily; or (iii) 7-day omeprazole, 20 mg, amoxicillin, 1000 mg, and clarithromycin, 500 mg, all twice daily. Endoscopy (CLO test, histology) was performed before randomization and 6 weeks after drug treatment. RESULTS: One hundred and seventy-three patients were randomized. H. pylori eradication rates (intention-to-treat, n=173/per protocol, n=167) were 88%/91% for 7-day rabeprazole-based therapy, 72%/72% for 3-day rabeprazole-based therapy and 82%/89% for 7-day omeprazole-based therapy, respectively. The per protocol eradication rate was significantly better in the 7-day rabeprazole-based therapy and 7-day omeprazole-based therapy groups when compared to the 3-day rabeprazole-based therapy group (P=0.01 and P=0.04, respectively). Compliance was excellent and all three regimens were well tolerated. CONCLUSIONS: The efficacy of seven-day rabeprazole-based triple therapy is similar to 7-day omeprazole-based triple therapy for the eradication of H. pylori infection.     

Furazolidone-based triple 'rescue therapy' vs. quadruple 'rescue therapy' for the eradication of Helicobacter pylori resistant to metronidazole

BACKGROUND: The optimal treatment of patients with Helicobacter pylori resistant to metronidazole has not been established. AIM: To compare the efficacy of quadruple and furazolidone-based triple therapy in the eradication of H. pylori resistant to metronidazole. METHODS: Duodenal ulcer patients (n = 70) in whom initial eradication therapy failed and who harboured H. pylori strains resistant to metronidazole were randomized to receive one of the following 7-day regimens: colloidal bismuth subcitrate, 240 mg, tetracycline, 750 mg, and furazolidone, 200 mg, each given twice daily (BTF), or omeprazole, 20 mg b.d., colloidal bismuth subcitrate, 240 mg b.d., tetracycline, 500 mg q.d.s., and metronidazole, 500 mg b.d. (OBTM). H.pylori status was assessed by culture, histology and rapid urease test before treatment and 4-6 weeks after therapy. Susceptibility to metronidazole was assessed by the agar dilution method. RESULTS: H. pylori eradication rates with intention-to-treat/per protocol analyses were: BTF, 85.7%/90.9%; OBTM, 74.2%/89.6%. Duodenal ulcers were healed in nine of 10 (90%) patients in the BTF group and in all patients (12/12) (100%) in the OBTM group (P = N.S.). A significantly lower rate of adverse events was observed in the BTF group than in the OBTM group (31.4% vs. 60%, P = 0.03), but there was no difference in terms of discontinuation of treatment (2/35 vs. 6/35, P = N.S.). CONCLUSIONS: The 1-week BTF regimen was as effective as the OBTM regimen, and produced less adverse events. Thus, it may be used in patients in whom resistance of H. pylori to metronidazole is suspected.     

Clarithromycin vs. furazolidone in quadruple therapy regimens for the treatment of Helicobacter pylori in a population with a high metronidazole resistance rate

BACKGROUND: The eradication of Helicobacter pylori plays a pivotal role in the treatment of peptic ulcer disease. Metronidazole resistance, common in Iran, is claimed to be a major reason for the failure of metronidazole-containing regimens. Both clarithromycin and furazolidone are potential alternatives for metronidazole. AIM: To assess and compare the effectiveness of clarithromycin- and furazolidone-based regimens in eradicating H. pylori in a population with a high metronidazole resistance rate. METHODS: Patients with proven duodenal ulcer and H. pylori infection were randomly assigned to one of two groups. The patients received 2 weeks of omeprazole 20 mg b.d., amoxicillin 1000 mg b.d, bismuth subcitrate 240 mg b.d. and either clarithromycin 500 mg b.d. (the OABC group) or furazolidone 200 mg b.d. (the OABF group). RESULTS: A total of 118 patients were randomized, 55 in the OABC group and 63 in the OABF group. The intention-to-treat eradication rate was 84% and 85% for the OABF and OABC groups, respectively. The per protocol eradication rates were 90% for both groups. CONCLUSIONS: OABC and OABF are both effective in eradicating H. pylori in areas where metronidazole resistance is a problem. OABF is a good alternative in the face of growing resistance to clarithromycin in developed countries, and is attractive for developing countries where clarithromycin is not readily available.     

Low-dose furazolidone in triple and quadruple regimens for Helicobacter pylori eradication

BACKGROUND: Furazolidone-based regimens for the eradication of Helicobacter pylori are low cost and effective. Unfortunately, the usual dose of furazolidone is not tolerable in many patients. Lower doses of furazolidone are expected to cause fewer adverse effects. AIM: To investigate the efficacy of low-dose furazolidone in the eradication of H. pylori. METHODS: One hundred and fifty patients with duodenal ulcer and H. pylori infection were randomly assigned to one of three treatment groups: omeprazole 20 mg b.d., amoxicillin 1000 mg b.d. and furazolidone 100 mg b.d. for 14 days (OAF); omeprazole 20 mg b.d., amoxicillin 1000 mg b.d., furazolidone 100 mg b.d. and bismuth subcitrate 240 mg b.d. for 14 days (OABF1); or omeprazole 20 mg b.d., amoxicillin 1000 mg b.d., furazolidone 200 mg b.d. and bismuth subcitrate 240 mg b.d. for 14 days (OABF2). RESULTS: Of the 150 patients, 145 completed treatment. The intention-to-treat and per protocol eradication rates were 54% (27/50), 72% (36/50) and 92% (46/50) for the OAF, OABF1 and OABF2 groups, respectively. The OAF and OABF1 groups showed significantly lower eradication rates than the OABF2 group (P<0.001 and P<0.01, respectively). CONCLUSIONS: Triple and quadruple furazolidone-based H. pylori eradication regimens do not yield acceptable success rates when a low dose of furazolidone (100 mg b.d.) is used.     

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.