One-week therapy with pantoprazole versus ranitidine bismuth citrate plus two antibiotics for Helicobacter pylori eradication

AIM: A combination of omeprazole plus amoxycillin (Amo) and clarithromycin (CIa) for 7 days has been studied extensively. However, the role of other proton pump inhibitors, such as pantoprazole (Pan), in this therapy is not well known. On the other hand, ranitidine bismuth citrate (RBC) also seems to be effective when combined with Amo and CIa. Our aim was to evaluate and to compare these two novel short-term triple therapies (Pan+Amo+Cla and RBC+Amo+Cla) for treatment of Helicobacter pylori. METHODS: In a randomized clinical trial 150 consecutive patients (38 with duodenal ulcer, 112 with non-ulcer dyspepsia) infected by H. pylori were studied prospectively. Exclusion criteria were: previous H. pylori eradication therapy, gastroerosive drug use, gastric surgery, and associated diseases. One of two regimens was given for 7 days: Pan (40 mg b.i.d.), Amo (1 g b.i.d.), Cla (500 mg b.i.d.) (group Pan+Amo+Cla, n = 75); or RBC (400 mg b.i.d.), Amo (1 g b.i.d.), Cla (500 mg b.i.d.) (group RBC+Amo+Cla, n = 75). All drugs were administered together after meals. Compliance was evaluated by return tablet count. Data were analysed by univariate (chi2) and multivariate (multiple logistic regression) analysis. Eradication was defined as a negative 13C-urea breath test 1 month after completing therapy. RESULTS: The distribution of studied variables (age, gender, smoking, duodenal ulcer/non-ulcer dyspepsia) was similar in both therapy groups. Per-protocol eradication was achieved in 48/71 (68%) in group Pan+Amo+Cla, and in 61/70 (87%) in group RBC+Amo+Cla (P= 0.01). Intention-to-treat (ITT) eradication was achieved in, respectively, 48/ 75 (64%) and in 61/75 (81%) (P= 0.03). The RBC+ Amo+Cla regimen was more effective than Pan+Amo+Cla in non-ulcer dyspepsia patients (ITT, 84% vs 58%; P = 0.005), but statistically significant differences were not demonstrated in duodenal ulcer patients (72% vs 80%). In the multivariate analysis the odds ratio for the effect of the type of therapy on H. pylori eradication in patients with non-ulcer dyspepsia was 3.8 (95% Cl, 1.6-9.3; P = 0.003). No relevant adverse effects were reported with any regimen. CONCLUSION: A RBC+Amo+Cla regimen for only 1 week is a promising therapy for H. pylori infection, due to its high efficacy, simple posology, and excellent tolerability. Combination of Pan with Amo and Cla, although effective in duodenal ulcer patients, but in non-ulcer dyspepsia has not achieved the favourable results previously reported with other proton pump inhibitors.     

Gastric ulcer healing with ranitidine and cimetidine. A multicentre study

A single-blind study of 339 patients in 19 centres compared the efficacy and tolerance of ranitidine in treating endoscopically confirmed gastric ulcers. Ranitidine (150 mg twice daily) was compared with cimetidine (1 g daily in divided doses) over 4 weeks, followed by a second 4-week treatment for any patient whose ulcer was not healed. In 292 patients who completed the study, endoscopy showed healing in 69% of patients receiving ranitidine and 59% receiving cimetidine after 4 weeks, and 90% and 88%, respectively, by 8 weeks. These results were not significantly different, and, similarly, healing rates for different ulcer sites did not differ. There were no serious adverse drug reactions during the study. Ranitidine is an effective and safe treatment for healing gastric ulcers, with a tendency to produce a faster healing rate than cimetidine during the first 4 weeks of treatment.     

以枸橼酸铋雷尼替丁为基础的三联疗法根除幽门螺杆菌的系统评价

目的 评价国产枸橼酸铋雷尼替丁(瑞倍)根除幽门螺杆菌(H.pylori)的疗效.方法 检索1995年1月至2008年10月中国生物医学文献数据库(CBM)、手工检索发表与未发表的中文文献,应用国际Cochrane协作网系统评价方法 收集比较瑞倍为主的三联方案与质子泵抑制剂(PPI)治疗根除H.pylori的随机对照试验(RCT).数据采用RevMan 4.2进行统计分析.结果 12篇文献共1254例患者满足纳入标准.经meta分析显示,瑞倍根除H.pylori疗效和对照组比较差异无统计学意义(OR 1.30,95%CI:0.94～1.81,P=0.12).试验未发现严重副反应.结论 瑞倍为主的三联方案根除H.pylori是一个值得选用的治疗方法 .     

Gastroprotective effect of ranitidine bismuth citrate is associated with increased mucus bismuth concentration in rats.

BACKGROUND: Antisecretory and bismuth compounds protect the gastric mucosa from injury resulting from non-steroidal anti-inflammatory drugs. AIM: To study the mechanism underlying the gastroprotective effects of ranitidine bismuth citrate (GG311) in rats. METHODS: Indomethacin rat injury model and in vivo microscopy in which acid output, surface cell intracellular pH (pHi), gastric mucus gel thickness, and mucosal blood flow were measured simultaneously. RESULTS: In injury studies, GG311 dose dependently protected against severe injury induced by indomethacin (60 mg/kg subcutaneously). In in vivo microscopic studies, indomethacin significantly decreased mucus gel thickness and increased the initial rate of acidification of gastric surface cells when the superfusate pH was lowered from 7.4 to 1.0, and impaired pHi during acid exposure. Indomethacin had no effect on mucosal blood flow or acid output. GG311 alone had no effect on gel thickness, blood flow, or pHi homeostasis during acid exposure, but improved the initial acidification rate and pHi during superfusion with pH 1.0 solutions in the presence of indomethacin. In separate experiments, indomethacin pretreatment considerably increased gastric mucus bismuth concentrations in rats given GG311. CONCLUSIONS: The gastroprotective effect of GG311 against indomethacin induced gastric injury is associated with high and prolonged gastric mucus bismuth concentrations, which may impair proton permeation across the mucus gel.     

Duodenal ulcer healing with four antacid tablets daily

In a double-blind, randomized, multicenter trial in 80 consecutive outpatients with endoscopically verified duodenal ulcer, we have tested the ulcer-healing efficacy of a quite low dose of antacids, given only four times daily. The patients received one chewable aluminum-magnesium-antacid tablet (buffering capacity, 30 mmol/tablet) or placebo 1 h after meals and at bedtime. Re-endoscopy after 4 weeks of treatment showed healed ulcer in 28 of 38 patients (74%) in the antacid group, compared with 11 of 38 patients (29%) in the placebo group (p less than 0.001). The number of days and nights with ulcer pain was significantly less in the antacid group than in the placebo group during the treatment period. Thus, only four antacid tablets a day, with a total buffering capacity of 120 mmol/day, significantly promote duodenal ulcer healing and pain relief.     

Duodenal ulcer healing after presentation with haemorrhage.

Forty patients who were managed conservatively after haemorrhage from an endoscopically verified duodenal ulcer were randomised at discharge from hospital to enter a blind study of ranitidine therapy (150 mg bd) versus a placebo tablet. The patients were re-endoscoped after four weeks, ulcer status defined and the trial code broken revealing that five of 20 placebo patients had healed their duodenal ulcer compared with 16 of 20 ranitidine patients (p = 0.001). Lifestyle parameters of both groups improved during the study period but no directly related benefit in duodenal ulcer healing could be shown. We conclude that effective anti-ulcer therapy, such as ranitidine, is required to heal a duodenal ulcer which presents with haemorrhage.     

One-week dual therapy with ranitidine bismuth citrate and clarithromycin for the treatment of Helicobacter pylori infection in Brazilian patients with peptic ulcer

AIM: To assess the efficacy and safety of ranitidine bismuth citrate plus clarithromycin given for 1 wk in Brazilian patients with peptic ulcer. METHODS: One hundred and twenty patients with peptic ulcer were randomized in two treatment groups: (1)1-wk regimen consisting of ranitidine bismuth citrate 400 mg b.i.d. with clarithromycin 500 mg b.i.d. or (2) 2-wk regimen of the same treatment. Eradication of the infection was considered when both the histologic examination and the urease test were negative for the infection 3 mo after treatment. RESULTS: By intention to treat analysis, Helicobacter pylori (H pylori) was eradicated in 73% and 76% of patients, respectively treated for 1 or 2 wk (P>0.05). By per protocol analysis, the eradication rates were 80% and 83%, respectively, in patients treated for 1 or 2 wk (P>0.05). Nine patients (8.2%) reported minor side effects. CONCLUSION: One-week therapy with ranitidine bismuth citrate and clarithromycin is safe, well tolerated and effective for treatment of H pylori infection, and appears to be comparable to the 2-wk regimen in terms of efficacy.x     

Comparison of ranitidine bismuth citrate, tetracycline and metronidazole with ranitidine bismuth citrate and azithromycin for the eradication of Helicobacter pylori in patients resistant to PPI based triple therapy.

BACKGROUND/AIMS: Helicobacter pylori is the most common infectious disease all over the world. Ten to twenty percent of the patients remain infected despite treatment with proton pump inhibitors (PPIs), amoxicillin and clarithromycin. We compared PPI, bismuth, tetracycline and metronidazole with ranitidine bismuth citrate, tetracycline and metronidazole in cases resistant to PPIs-based triple therapies. METHODS: The study included 52 patients who underwent a triple therapy with PPI, clarithromycin and amoxicillin for 14 days between September 2001 and December 2002, and were found to be resistant to the therapy. They were randomized to take ranitidine bismuth citrate (Rb) 400 mg twice a day, tetracycline (T) 1 g twice a day and metronidazole (M) 500 mg three times a day for 14 days (RbTM), or ranitidine bismuth citrate (Rb) 400 mg twice a day for 14 days and azithromycin (A) 500 mg once a day for 7 days (RbA). Four weeks after the treatment, endoscopies were repeated, and patients were assessed with respect to changes in symptoms. When H. pylori was negative on histological analysis and urease test, eradication was achieved. RESULTS: A total of 52 patients, 32 females and 20 males with a mean age of 49+/-12 years, were included in the study. Eradication was achieved in 15 (28%) out of 52 patients in total. There was a significant difference between RbA and RbTM groups (p=0.01). In fact, H. pylori was eradicated in 3 (12%) out of 25 patients in the RbA group, whereas it was eradicated in 12 (44.4%) out of 27 patients in the RbTM group. Symptom scores significantly improved in both groups after the treatment, though there was not a significant difference between the groups (p=0.705). CONCLUSIONS: Triple therapy including azithromycin does not seem to be a good choice in cases resistant to the first line therapies; however, a similarly lower rate of eradication was achieved with the quadruple therapy proposed. Therefore, different treatment schemes should be applied in resistant patients, and further studies are needed as well.     

One-week ranitidine bismuth citrate versus colloidal bismuth subcitrate-based anti-Helicobacter triple therapy: a prospective randomized controlled trial

OBJECTIVE: The efficacy of 1 wk bismuth triple therapy is adversely influenced by the presence of metronidazole resistance. In vitro studies suggest that ranitidine bismuth citrate (RBC) plus metronidazole exhibit synergistic activity against metronidazole resistant strains of Helicobacter pylori (H. pylori). Whether this confers a superior clinical efficacy remains unproven. This study compared the efficacy of RBC-based triple therapy with bismuth triple therapy in eradication of H. pylori. METHODS: Patients with H. pylori-related ulcer disease or gastritis were randomized to receive either 400/mg of RBC twice daily plus 400/mg of metronidazole and 500/mg of tetracycline four times daily for 1 wk (RMT) or 120/mg of colloidal bismuth subcitrate, 400/mg of metronidazole, and 500/mg of tetracycline, all given four times daily for 1 wk (BMT). Metronidazole susceptibility was determined by the E-test and pretreatment resistance was defined as minimum inhibitory concentration > or = 32/mg/L. RESULTS: Of 100 consecutive patients randomized, two patients were lost to follow-up in each group. Forty-three of 85 (51%) H. pylori isolates were metronidazole resistant. Per-protocol cure rate for RMT and BMT was 40 of 41 (98%) and 37 of 44 (84%), respectively (p = 0.058). Intent-to-treat cure rate for RMT and BMT was 46 of 50 and 41 of 50, respectively (92% vs 82%, p = 0.23). A significantly higher eradication of metronidazole resistant H. pylori was observed in the RMT group (25 of 25, 100%) than in the BMT group (12 of 16, 75%), (p = 0.018). Side effects observed in the two treatment groups were comparable. CONCLUSIONS: One week of RBC triple therapy with metronidazole and tetracycline is an effective anti-Helicobacter therapy. This regimen is more appropriate in areas of high prevalence of metronidazole resistance.     

Gastric ulcer healing: a comparison of enprostil versus ranitidine

Enprostil is a synthetic prostaglandin E2 analogue with gastric antisecretory and mucosal protective properties. We compared the effects of enprostil and ranitidine on the healing of gastric ulcers and the subsequent relapse rates over 6 months. Patients (N = 156) were recruited for a double-blind study from 12 centers in Europe; 71 were randomly assigned to oral treatment with 35 micrograms enprostil twice daily and 85 to 150 mg ranitidine twice daily for up to 8 weeks. Both groups were of similar demography; their healing rates were also similar. Cumulative intent-to-treat healing rates were at 4 weeks enprostil 48%, ranitidine 41%: at 6 weeks enprostil 65%, ranitidine 68%; and at 8 weeks enprostil 72%, ranitidine 80%. Of those patients who met all protocol criteria and completed treatment, and were endoscoped at the prescribed times, healing rates were at 4 weeks enprostil 55%, ranitidine 54%, at 6 weeks enprostil 75%, ranitidine 84%; and at 8 weeks enprostil 80%, ranitidine 90%. Relief of pain was rapid and similar in both groups. The incidence of adverse events was low and similar in the two groups. The treatment-free relapse rate at 6 months was enprostil 64%, ranitidine 49%; the median times to relapse were 169 and 203 days, respectively. Enprostil and ranitidine appear to be equally effective in healing gastric ulcers.     

A single-centre study of gastric ulcer healing with 300 mg ranitidine at night versus 150 mg ranitidine twice daily

In a single-centre study 59 patients with gastric ulcer were treated either with 300 mg ranitidine at night or with 150 mg ranitidine twice daily. After 4 and 8 weeks 73% and 97%, respectively, of those treated with 300 mg at night and 59% and 86% of those treated with 150 mg twice daily had complete ulcer healing. These differences between the two groups were not statistically significant. No serious side effects were seen. Ranitidine, 300 mg at night, appears to be at least as effective as the standard 150 mg twice daily regimen in the treatment of gastric ulcer.     

Effect of ranitidine bismuth citrate on postprandial plasma gastrin and pepsinogens.

Ranitidine bismuth citrate was compared with an equipotent dose of ranitidine, to determine whether the former, by an anti-Helicobacter pylori activity, would counteract the rise of gastrin resulting from ranitidine's gastric acid antisecretory activity. Twenty four men with duodenal ulcers were studied before and on the 8th day of dosing with either ranitidine bismuth citrate 800 mg twice daily or ranitidine 300 mg twice daily (double blind, randomised, parallel groups). Fasting and postprandial plasma gastrin and plasma pepsinogen I and II concentrations were measured, and a 13C-urea breath test was performed before and on the 8th day of dosing. The 13C-urea breath tests were positive in 21 patients before dosing and remained positive in nine of nine of the ranitidine dosed patients, whereas only two of 12 patients treated with ranitidine bismuth citrate remained positive. The expected rise in meal stimulated plasma gastrin with ranitidine was seen in the 12 patients who received ranitidine but, despite suppression of H pylori urease activity in 10 of 12 patients taking ranitidine bismuth citrate, there was no attenuation of the meal stimulated gastrin rise. There was no significant difference in the mean derived (4 hour) plasma pepsinogen I and II concentrations after dosing with ranitidine or ranitidine bismuth citrate.     

Duodenal ulcer treated with omeprazole: healing and relapse rates. Does treatment duration influence subsequent remission?

One hundred and twenty-nine patients were studied with regard to healing of duodenal ulcers with 30 mg omeprazole once daily, recurrence rates after 2 and 4 weeks' treatment in patients with ulcers healed after 2 weeks, and recurrences in rapid and slow healers. Cumulative healing rates were 77% and 98% after 2 and 4 weeks, respectively. Eighty-one patients (65%) were without ulcer symptoms after 2 weeks, and 43 (34%) were improved. Seven of 45 patients (16%; 95% confidence limits, 6-30%) with ulcers healed after 2 weeks had relapsed after another 2 weeks of placebo; 3 were asymptomatic. The overall relapse rate after 6 months was 62%. There were no statistically significant differences in relapse rates between 2 and 4 weeks' treatment of patients with ulcers healed after 2 weeks or between rapid and slow healers. Ulcer size, smoking habits, and alcohol consumption were not significantly related to healing or relapse.     

Ten-day triple therapy with ranitidine bismuth citrate, amoxicillin, and clarithromycin in eradicating Helicobacter pylori

OBJECTIVE: Fourteen-day therapy with ranitidine bismuth citrate, amoxicillin, and clarithromycin has been shown to have a high Helicobacter pylori eradication rate (> 90%) in U.S. trials. The aim of this study was to determine the H. pylori eradication rate of a ranitidine bismuth citrate-based triple regimen of shorter duration (10 days), which has been shown to be effective in Europe. METHODS: Dyspeptic patients who had a positive baseline 13C-urea breath test and either a positive antral rapid urease test or positive IgG serology were studied. Treatment consisted of ranitidine bismuth citrate 400 mg, clarithromycin 500 mg, and amoxicillin 1 g, all given b.i.d. for 10 days. Eradication was determined >4 wk after completion of therapy by the 13C-urea breath test (enrichment <2.4%). Results are expressed for intent-to-treat (all patients randomized even if they did not take the drug) and per-protocol (major protocol violators excluded) analyses. RESULTS: Seventy-seven patients with a mean age of 48 +/- 1.8 yr were studied. Forty-eight patients had eradication of H. pylori with this regimen (62%), 16 patients (21%) did not have eradication, and 13 patients (17%) did not return for breath testing. By intent-to-treat analysis the eradication rate was 62% (95% confidence intervals [CI], 51%, 73%) and by per-protocol analysis the eradication rate was 75% (95% CI, 63%, 85%). CONCLUSIONS: Ten-day, twice-daily therapy with ranitidine bismuth citrate, amoxicillin, and clarithromycin has an eradication rate that ranges from 62-75%. Fourteen-day therapy may be preferable because of higher eradication rates.     

Ulcer healing and relapse prevention by ranitidine in peptic ulcer disease

Ranitidine, 300 mg daily, was given to 92 patients with duodenal ulcer (DU), 38 with prepyloric ulcer (PPU), and 21 with gastric corporeal ulcer (GCU). The healing rates at 4 weeks differed for the different types of ulcers (P less than 0.01), being 91% for DU, 68% for PPU, and 81% for GCU. After established ulcer healing, maintenance treatment with either ranitidine, 100 mg twice daily or 150 mg at night, or placebo was given for 1 year or until ulcer relapse in a total of 108 patients--71 with DU, 24 with PPU, and 13 with GCU. There were no significant differences in relapse rates between the two groups treated with active drug or between the three ulcer groups. However, the overall relapse rate in the active drug groups was 16%, against 72% in the placebo group (P less than 0.001).     

Helicobacter pylori infection in childhood: results of management with ranitidine bismuth citrate plus amoxicillin and tinidazole

BACKGROUND AND AIMS: To verify whether a triple therapy bismuth citrate plus amoxicillin and tinidazole eradicates H. pylori infection in pediatric patients. METHODS: Fifty children (30 females; mean age 12.4 +/- 1.1 years, range 10-15 years) suffering from upper abdominal complaints and Helicobacter pylori (H. pylori)-associated gastroduodenal disease were treated with a 4 week course of ranitidine bismuth citrate (400 mg, twice daily) plus oral tinidazole (20 mg/kg) and amoxicillin (50 mg/kg) for the first 2 weeks. RESULTS: The endoscopic diagnoses were: esophagitis (seven cases), gastritis (six cases), gastroduodenitis (43 cases), duodenitis (one case), gastric ulcer (two cases) and duodenal ulcer (13 cases). Helicobacter pylori was eradicated in 40 (80%) patients and clinical improvement was noticed in 39 (78%) of symptomatic subjects. Duodenal ulcers were healed in all the children, but lymphoid nodular hyperplasia was persistent in all patients, independent of the H. pylori status. The potentially drug-related adverse events (blackening of the tongue, six patients; diarrhea, one patient; disturbance of taste, two patients) were registered in seven (14%) patients and dark stools were observed in 48 (96%) patients. No children withdrew from the study because of either side-effects or clinical laboratory changes. No patient had toxic levels of blood bismuth (values ranged between 2.1 and 5.4 microg/L, mean value 3.4 +/- 1.04 microg/L). CONCLUSIONS: Findings suggest that the present treatment regimen is effective enough in the resolution of H. pylori-associated peptic ulcer disease of childhood.