兰索拉唑每日15mg与每日30mg治疗消化性溃疡的比较

目的：探索兰索拉唑１５ｍｇ／ｄ和３０ｍｇ／ｄ治疗消化性溃疡的比较。方法：６３例经胃镜证实为活动性消化性溃疡病人，随机分成１５ｍｇ／ｄ组３３例，３０ｍｇ／ｄ组３０例，疗程均为４ｗｋ。疗程结束后３ｄ内复查胃镜。结果：用药４ｗｋ胃镜下溃疡愈合率（疤痕期或溃疡消失）１５ｍｇ／ｄ组为８５％，３０ｍｇ／ｄ组为８７％。２组总有效率各为１００％（Ｐ＞０．０５）。服药后中上腹疼痛消失及反酸症状消失，１５ｍｇ／ｄ组与３０ｍｇ／ｄ组依次为５．９±ｓ１．８ｄ，４．５±１．８ｄ与３．２±１．４ｄ，３．０±１．０ｄ。２组差别均有非常显著意义（Ｐ＜０．０１）。结论：口服兰索拉唑１５ｍｇ／ｄ总有效率与口服３０ｍｇ／ｄ相仿，但疼痛和反酸症状消失３０ｍｇ／ｄ组比１５ｍｇ／ｄ组更快     

Double-blind comparison of lansoprazole 15 mg, lansoprazole 30 mg and placebo as maintenance therapy in patients with healed duodenal ulcers resistant to H2-receptor antagonists

BACKGROUND: Maintenance antisecretory therapy is often used to prevent duodenal ulcer recurrence and control symptoms. This study compared the efficacy and safety of lansoprazole 15 mg and 30 mg daily with placebo in preventing ulcer recurrence in patients with a recent history of duodenal ulcer disease. METHODS: Fifty-six patients were treated with either lansoprazole 15 mg, 30 mg or placebo o.m. RESULTS: Within 1 month of study initiation, 27% (four out of 15) of placebo-treated patients experienced ulcer recurrence as compared to 13% (two out of 15) and 6% (one out of 18) of lansoprazole 15 mg and 30 mg treated patients, respectively. Median time to first ulcer recurrence was > 12 months in lansoprazole patients. At Month 12, significantly (P < 0.001) more lansoprazole 15 mg patients (70%) and lansoprazole 30 mg patients (85%) remained healed. Eighty-two per cent of lansoprazole 15 mg and 76% of lansoprazole 30 mg patients remained asymptomatic during the entire study period. All placebo patients became symptomatic, experienced ulcer recurrence, or withdrew from the study by month six. The incidence of adverse events was comparable among the three treatment groups. CONCLUSIONS: Lansoprazole safely and effectively reduces duodenal ulcer recurrence and ulcer-related symptoms.     

Morning versus evening dosing of lansoprazole 30 mg daily on twenty-four-hour intragastric acidity in healthy subjects

Background : Morning dosing is usually recommended with proton pump inhibitors, but there are few data from 24-h intragastric acidity studies comparing times of dosing.
Methods : A double-blind, placebo-controlled study was performed on the seventh day of dosing to compare the effects of lansoprazole 30 mg given either in the morning or evening on 24-h intragastric acidity in 32 healthy volunteers.
Results : The median integrated 24-h intragastric acidity on the seventh day of morning dosing with lansoprazole 30 mg was decreased to 36% of the placebo value, compared with 42% for evening dosing. For each daytime meal-related interval, morning dosing was significantly more effective for controlling acidity, but there was no significant difference between the regimens during the night interval (23.00–08.00 h).
Conclusions : These data favour morning dosing of lansoprazole 30 mg for routine use, but patients with mainly nocturnal symptoms may be best treated by evening dosing.     

Intravenous esomeprazole 40 mg vs. intravenous lansoprazole 30 mg for controlling intragastric acidity in healthy adults

Background  Intravenous (IV) formulations of proton pump inhibitors are effective for patients in whom oral therapy is not appropriate.
Aim  To compare IV esomeprazole and IV lansoprazole for the control of intragastric pH.
Methods  In this open-label crossover study, healthy, Helicobacter pylori -negative adults were randomized to one of two treatment sequences, each consisting of two 5-day dosing periods of IV esomeprazole 40 mg or IV lansoprazole 30 mg. Twenty-four-hour intragastric pH monitoring was conducted on days 1 and 5 of each dosing period.
Results  On days 1 and 5, intragastric pH was >4.0 significantly longer with esomeprazole than lansoprazole (least-squares means: day 1, 40.0% vs. 33.6%; day 5, 61.9% vs. 45.4%; both P  <   0.0001). During the first 4 h of pH monitoring, intragastric pH was >4.0 significantly longer on days 1 and 5 with esomeprazole than lansoprazole ( P  <   0.0001). Kaplan–Meier estimates of median hours to stable pH >4.0 were 4.92 for esomeprazole and 5.75 for lansoprazole ( P  =   0.0014 for test on Gehan scores).
Conclusion  In healthy adults, IV esomeprazole 40 mg controlled intragastric acidity faster and more effectively than IV lansoprazole 30 mg.     

Efficacy of esomeprazole 40 mg vs. lansoprazole 30 mg for healing moderate to severe erosive oesophagitis

BACKGROUND: Secondary analyses from previous studies indicated that esomeprazole was more effective than lansoprazole and omeprazole in healing moderate or severe (Los Angeles grades C or D) erosive oesophagitis (EE). AIM: To compare prospectively healing rates with esomeprazole vs. lansoprazole in patients with moderate to severe EE. METHODS: In this multicentre, randomized, double-blind, parallel-group trial, adult patients with endoscopically confirmed moderate or severe EE received esomeprazole 40 mg (n = 498) or lansoprazole 30 mg (n = 501) once daily for up to 8 weeks. The primary end point was EE healing through week 8. Secondary assessments included investigator-assessed resolution of symptoms and safety and tolerability. RESULTS: Time to healing was significantly different (P = 0.007), favouring esomeprazole. Estimated healing rates at week 8 were 82.4% with esomeprazole 40 mg and 77.5% with lansoprazole 30 mg. Heartburn resolved at week 4 in 72% and 64% of patients who received esomeprazole and lansoprazole, respectively (P = 0.005). Control of other GERD symptoms was similar between treatments. Both treatments were well tolerated. CONCLUSIONS: With 8 weeks' treatment, esomeprazole 40 mg once daily heals moderate to severe EE faster and in more patients, and resolves heartburn in more patients after 4 weeks of treatment, than lansoprazole 30 mg once daily.     

On-demand treatment of gastro-oesophageal reflux symptoms: a comparison of ranitidine 75 mg with cimetidine 200 mg or placebo

Aim:

To compare the effects of ranitidine 75 mg with those of either cimetidine 200 mg or placebo given on demand for relief of typical symptoms of gastro-oesophageal reflux disease during a 15-day period.

Methods:

A total of 1336 patients (aged ≥ 18 years) with heartburn episodes were recruited and randomly assigned to a ranitidine 75 mg, cimetidine 200 mg or placebo group. Depending on the occurrence or persistence of heartburn, treatment was administered as required up to three times daily, with at least 2 h between drug doses. Antacids were allowed as rescue medication if symptoms persisted for at least 2 h after the third medication on any given day. The primary end-point was defined as the proportion of patients with relief of at least 75% of heartburn episodes during the study period (i.e. relief occurring within 2 h after drug ingestion and lasting for at least 5 h).

Results:

Analysis was performed in an intention-to-treat population comprising 504 subjects in the ranitidine group, 515 in the cimetidine group and 270 in the placebo group. Primary end-point success rates were 41, 38 and 28%, respectively, for the three groups (P < 0.001 for ranitidine vs. placebo, P = 0.274 for ranitidine vs. cimetidine). Ranitidine 75 mg was significantly more effective than placebo in providing overall heartburn relief (P < 0.001). The differences between the ranitidine and cimetidine groups were not significant, except for a greater reduction in heartburn frequency in the ranitidine group at the end of the study period (P < 0.05). Drug dose was lower and less rescue medication was used in the ranitidine group than the placebo group . The three treatment groups did not differ in terms of tolerability.

Conclusion:

On-demand ranitidine 75 mg or cimetidine 200 mg are safe and effective treatment for reflux-related symptoms.

     

Treatment of patients with heartburn without endoscopic evaluation: on-demand treatment after effective continuous administration of lansoprazole 15 mg

Background : Relapse is frequent after initial treatment for gastro‐oesophageal reflux. An alternative strategy to intermittent or continuous therapy may be on‐demand treatment. Aim : To compare the efficacy and safety of on‐demand lansoprazole 15 mg and placebo treatment in patients with gastro‐oesophageal reflux. Methods : This was a multicentre, randomized, double‐blind study in two parallel groups of patients. In the acute study phase, all included patients (n = 203) were treated with lansoprazole 15 mg (once per day) for 4 weeks. At week 4, asymptomatic patients entered the 6‐month, on‐demand, follow‐up phase and were randomized to receive either lansoprazole 15 mg (once per day) or placebo. Results : A higher percentage of patients in the lansoprazole group completed the 6‐month follow‐up than in the placebo group [81% vs. 61% (P = 0.003)]. Only 16% of patients in the lansoprazole group discontinued the study for insufficient control of heartburn vs. 28% in the placebo group (P = 0.046). The mean daily intake in patients who completed the study was 1–5 capsules/day in the lansoprazole 15 mg group. Conclusions : On‐demand treatment with lansoprazole 15 mg in symptomatic patients after short‐term, continuous treatment is a promising therapeutic alternative to intermittent and continuous treatment to maintain heartburn control in patients with gastro‐oesophageal reflux.     

A comparison of three doses of lansoprazole (15, 30 and 60 mg) and placebo in the treatment of duodenal ulcer

Background: Lansoprazole is a new proton pump inhibitor for the treatment of peptic ulcer disease. Methods: A double-blind, multicentre study was undertaken in 2 9 6 patients with endoscopically proven duodenal ulcer to compare the efficacy and safety of lansoprazole 15, 30 or 60 mg with placebo. Ulcer healing was documented by endoscopy at 2 and 4 weeks; patients whose ulcers healed after 4 weeks were followed for up to 6 months post-treatment. Results: Four-week healing rates of 89.4% 91.7% and 89.9% were obtained with lansoprazole 15, 30 and 60 mg, respectively, compared with 46.1 % on placebo (P < 0.001). All three doses of lansoprazole produced rapid symptom relief, although patients taking 60 mg lansoprazole required fewer antacids than did those taking 15 mg. At 6 months, the percentages of patients healed were 45.3%, 40.0% and 38.4% in the lansoprazole 15, 30 and 60 mg dosage groups, respectively, and 2 5.3 % for the placebo group. No significant adverse events were documented during the period of this trial. Conclusion: Lansoprazole is an effective and safe treatment for duodenal ulcer and the 15 mg dose is as effective as 30 or 60 mg.     

Double-blind, placebo-controlled comparison of rabeprazole 20 mg vs. omeprazole 20 mg in the treatment of erosive or ulcerative gastro-oesophageal reflux disease

Background:

Rabeprazole sodium is the most recent member of a class of substituted benzimidazole molecules known as proton pump inhibitors. Other proton pump inhibitors have been shown to be effective in healing oesophagitis.

Methods:

In this randomised, double-blind, multicentre study, conducted at 27 European sites, the efficacy and safety of rabeprazole and omeprazole were compared in patients with erosive or ulcerative gastro-oesophageal reflux disease (GERD).100 patients received rabeprazole 20 mg, and 102 patients omeprazole 20 mg once daily for 4 or 8 weeks, with healing monitored by endoscopy.

Results:

Overall GERD healing rates observed and evaluated at weeks 4 and 8 were equivalent. Four-week healing rates for rabeprazole and omeprazole were 81%–81% and 92%–94% for 8-week healing. Rabeprazole-treated patients had similar relief of the frequency and intensity of heartburn to those treated with omeprazole. Both drugs were well tolerated over the 8-week treatment period. Mean changes in fasting serum gastrin were comparable. No significant differences in laboratory parameters were seen. Biopsies for argyrophil ECL cell histology at the end-point revealed a similar distributions of hyperplasia grades to those at baseline in both groups. Biopsies of body and antral mucosa for other parameters were similar between treatments for Helicobacter pylori colonization, presence or degree of inflammation, atrophy or intestinal metaplasia at the end-point.

Conclusion:

In this study, GERD healing rates following rabeprazole 20 mg once daily were equivalent to those obtained with omeprazole 20 mg once daily. Both treatments resulted in a comparable relief of the frequency and intensity of heartburn associated with this disease, and both were well tolerated.

     

Gatifloxacin 200 mg or 400 mg once daily is as effective as ciprofloxacin 500 mg twice daily for the treatment of patients with acute pyelonephritis or complicated urinary tract infections

The efficacy and safety of two oral dosing regimens of gatifloxacin were compared to ciprofloxacin in the treatment of complicated urinary tract infection in a randomised, double-blind multi-centre trial. One thousand one hundred and twenty-three adult patients with complicated urinary tract infection (70%) or pyelonephritis (30%) were initially enrolled, 1122 were treated. Of these, 824 were included in a modified ITT population: gatifloxacin 200 mg (274 patients) or 400 mg (280 patients) once daily or ciprofloxacin 500 mg twice daily for 5-14 days (269 patients). Bacteriological and clinical responses were assessed 7-9 days after the end of treatment (EOT) and 4-6 weeks post-treatment (end of study visit, EOS). The bacteriological response rates per patient at EOT in the gatifloxacin 400 mg, gatifloxacin 200 mg and ciprofloxacin groups were 77% (207/269), 78% (208/268) and 73% (190/259), respectively. At EOS they were slightly lower: 70% (184/262), 71% (176/248) and 69% (174/252), respectively. The clinical responses at EOT were 69% (190/277), 70% (190/273) and 65% (174/266). At EOS they were 71% (193/273), 70% (182/259) and 74% (190/258). The overall eradication rates of initial pathogens at EOT and EOS were 85.3% and 88.4% in the gatifloxacin 400 mg group; 84.1 and 90.1% in the gatifloxacin 200 mg group and 85.1 and 91.4% in the ciprofloxacin group. Both oral regimens of gatifloxacin were as effective as that of ciprofloxacin. All treatment groups showed a similar safety profile, nausea being the most frequently reported adverse event.     

A randomized trial in primary biliary cirrhosis comparing ursodeoxycholic acid in daily doses of either 10 mg/kg or 20 mg/kg

Background:

Ursodeoxycholic acid (UDCA) prolongs transplantation-free survival in primary biliary cirrhosis (PBC). However, the optimal therapeutic dose has not been established.

Aim:

To compare the effects of UDCA administered in daily doses of 10 vs. 20 mg/kg on symptoms, liver biochemistry and biliary UDCA enrichment.

Methods:

A 6-month multicentre randomized open controlled trial was conducted to assess the effects of an increase in the dose of UDCA to 20 mg/kg/day vs. continuation of 10 mg/kg/day for patients who had not achieved biochemical normalization during treatment for at least 6 months with the 10 mg/kg dose. Clinical and laboratory evaluations were performed at entry and at 3-month intervals. The percentage UDCA in duodenal bile was assessed at entry and at 6 months.

Results:

Sixty-one patients were enrolled. No side-effects of UDCA were observed. Within the 20 mg/kg/day group significant decreases were found for alkaline phosphatase (? 8%; P = 0.003), aspartate aminotransferase (? 11%; P = 0.01), alanine aminotransferase (? 17%; P < 0.001), γ-glutamyl transferase?(? 34%; P < 0.001), immunoglobulin M (? 11%; P = 0.002) and cholesterol (? 8.1%; P < 0.001). In the 10 mg/kg group none of these parameters differed significantly from baseline. No significant differences between dose groups for symptom scores or serum bilirubin were found. Biliary enrichment with UDCA increased from 37% to 46% in the 20 mg/kg group (P = 0.02) while remaining stable in the 10 mg/kg group.

Conclusions:

Liver biochemistry improved in PBC patients receiving UDCA 20 mg/kg/day compared to a dose of 10 mg/kg/day. Both doses were equally well tolerated. These results indicate that UDCA 10 mg/kg/day is a suboptimal dose for treating PBC.

     

Randomised clinical trial: twice daily esomeprazole 40 mg vs. pantoprazole 40 mg in Barrett's oesophagus for 1 year

Aliment Pharmacol Ther 2011; 33: 1019–1027

Summary

Background Barrett’s oesophagus is regarded as the most important risk factor for development of oesophageal adenocarcinoma. According to current guidelines, treatment should be limited to symptomatic Barrett’s oesophagus. Aim To evaluate the expression of Ki67, cyclooxygenase‐2 (COX‐2) and apoptosis in Barrett’s oesophagus after 12 months of double‐dose proton pump inhibitor therapy. The effectiveness of esomeprazole and pantoprazole was also compared. Methods Seventy‐seven nondysplastic Barrett’s oesophagus patients underwent baseline upper endoscopy. Patients were then randomised into two groups: one group was allocated to receive esomeprazole 40 mg b.d. and the other group pantoprazole 40 mg b.d. for 12 months. A follow‐up endoscopy was performed at the end of treatment. Sixty‐five of 77 patients agreed to undergo oesophageal manometry and 24‐h pH‐metry. Barrett’s oesophagus biopsies, obtained at baseline and after treatment, were analysed using immunohistochemistry to assess Ki67 and COX‐2 expression; apoptosis was evaluated using TUNEL. Results In the esomeprazole group, a significant decrease in Ki67 and COX‐2 expression, as well as an increase in apoptosis, were observed (P < 0.05). By contrast, in the pantoprazole group Ki67, COX‐2 and apoptosis did not vary significantly from baseline. By 24‐h oesophageal pH‐monitoring, a normal acid exposure time was recorded in patients treated with esomeprazole, while those allocated to pantoprazole displayed abnormal acid exposure (P < 0.05). Conclusions Treatment of Barrett’s oesophagus patients with high‐dose esomeprazole, but not pantoprazole, promoted a decrease in proliferative markers, concomitantly with a decrease in apoptotic cell death. Moreover, esomeprazole allowed a better oesophageal acid control than pantoprazole.     

Efficacy and tolerability of lumiracoxib 100 mg once daily in knee osteoarthritis: a 13-week, randomized, double-blind study vs. placebo and celecoxib

OBJECTIVE: To determine the efficacy and safety of lumiracoxib for knee osteoarthritis (OA). METHODS: This was a 13-week, multicentre, randomized, double-blind, double-dummy, placebo-controlled study. Males or females aged >/= 18 years with primary knee OA received lumiracoxib 100 mg od, lumiracoxib 100 mg od with a loading dose of 200 mg od for the first two weeks, celecoxib 200 mg od, or placebo. MAIN OUTCOME MEASURES: Co-primary variables, assessed at week 13, were OA pain intensity in the target knee, patient's global assessment of disease activity and the WOMAC total score. Other variables included OMERACT-OARSI responder rates and WOMAC subscale scores. Safety and tolerability were evaluated. RESULTS: All active treatments were superior to placebo for all co-primary variables. No significant differences were observed between any active treatments. Mean reductions from baseline to week 13 for lumiracoxib 100mg od, 100mg od with loading dose, celecoxib and placebo, respectively, were: OA pain intensity in the target knee: 26.8, 26.2, 26.6 and 21.4mm (all p < 0.01 vs. placebo); patient's global assessment of disease activity: 25.1, 21.9, 22.9 and 18.9 mm (all p < 0.05 vs. placebo); WOMAC total score: 15.2, 14.8, 14.7 and 11.3 (all p < 0.01 vs. placebo). Lumiracoxib was superior to placebo and similar to celecoxib for OMERACT-OARSI response and WOMAC subscale scores. Lumiracoxib was well tolerated. The incidence of adverse events was similar across groups. CONCLUSIONS: Lumiracoxib 100 mg od provided effective relief from the pain of knee OA, with efficacy similar to celecoxib 200 mg od, and was well tolerated.     

Double-blind, randomized controlled study to assess the effects of lansoprazole 30 mg and lansoprazole 15 mg on 24-h oesophageal and intragastric pH in Chinese subjects with gastro-oesophageal reflux disease

BACKGROUND: Previous studies have suggested that the acid secretory capacity of the Chinese population is lower than that of the Western population. AIM: To compare the effect of lansoprazole 30 mg and 15 mg once daily on the 24-h oesophageal and intragastric pH profiles in Chinese patients with gastro-oesophageal reflux disease. METHODS: Forty-four patients (male to female ratio, 27 : 17; mean age, 53 years; 55% with oesophagitis) with gastro-oesophageal reflux disease were randomized to receive lansoprazole 30 mg or 15 mg once daily for 4 weeks. Measurement of the 24-h oesophageal and intragastric pH, gastro-oesophageal reflux disease symptoms and quality of life was performed at baseline and during the last week of each dosing period. RESULTS: Lansoprazole 30 mg maintained an intragastric pH > 4 for 10.5 h vs. 9.6 h for lansoprazole 15 mg (P = 0.44). The percentage total time at oesophageal pH < 4 was similar for lansoprazole 30 mg and 15 mg (2.0% vs. 2.3%, P = 0.30). The proportion of patients with complete cure of heartburn and acid regurgitation and the quality of life assessment were similar for lansoprazole 30 mg and 15 mg. Both dosages of lansoprazole were well tolerated and the compliance was 100% in both groups. CONCLUSION: Lansoprazole dosages of 30 mg and 15 mg once daily provide a satisfactory decrease for oesophageal acid exposure and are equally effective for the treatment of gastro-oesophageal reflux disease in the Chinese population.     

Clinical trial: chest pain caused by presumed gastro‐oesophageal reflux in coronary artery disease – controlled study of lansoprazole vs. placebo

Aliment Pharmacol Ther 2010; 32: 191–199

Summary

Background Gastro‐oesophageal reflux (GER) and coronary artery disease commonly co‐exist. Coronary artery disease patients may mistake GER‐induced pain for cardiac pain or GER might provoke angina. Aim To investigate if GER might contribute to nocturnal/rest chest pain among coronary artery disease patients. Methods Double‐blind placebo‐controlled crossover study investigating effect of lansoprazole on chest pain; 125 patients with angiographically proven coronary artery disease enrolled with at least one weekly episode of nocturnal/rest pain, randomized to lansoprazole 30 mg daily or placebo with crossover after 4 weeks. Symptoms recorded and QOL assessed by Nottingham Health Profile Questionnaire; ST segment depression episodes counted from 24 h electrocardiographic monitoring in final week of both periods. Statistical analysis: ANCOVA with period and carryover analysis. Results In all, 108 patients completed the study. There was a modest increase in pain‐free days on lansoprazole vs. placebo (P < 0.02), with fewer days with pain at rest (P < 0.05) and at night (P < 0.009) on lansoprazole vs. placebo, but no significant differences in ST segment depression episodes (P = 0.64). There was a trend for reduction in the ‘physical pain’ QOL domain. Conclusions Among coronary artery disease patients, lansoprazole modestly increases pain‐free days and reduces rest/nocturnal pain. As lansoprazole did not affect ST segments, this may be by suppression of GER‐provoked pain misinterpreted as angina, rather than acid‐provoked ischaemia.     

Comparison of rabeprazole 20 mg vs. omeprazole 20 mg in the treatment of active gastric ulcer—a European multicentre study

Background:

Rabeprazole sodium is the newest member of a class of substituted benzimidazole molecules known as proton pump inhibitors. Other proton pump inhibitors have been shown to be effective in healing active, benign gastric ulcers.

Methods:

In this randomized, double-blind, multicentre study, conducted at 25 European sites, rabeprazole and omeprazole were compared in patients with active gastric ulcers. Two hundred and twenty-seven patients with active benign gastric ulcer were randomized to receive either rabeprazole 20 mg (n = 113) or omeprazole 20 mg (n = 114) once daily for 3 or 6 weeks, with healing monitored by endoscopy.

Results:

After 3 weeks, complete healing (ITT analysis) was documented in 58% of patients given rabeprazole and 61% in patients given omeprazole (N.S.). After 6 weeks the healing rates were identical in both groups at 91%. Rabeprazole-treated patients had numerically greater symptom relief at all 12 points of comparison. The differences significantly favoured rabeprazole at week 3 for daytime pain improvement (P = 0.023) and at week 6 for pain frequency (P = 0.006) and complete resolution of night pain (P = 0.022). Both drugs were well-tolerated over the 6-week treatment course. Mean changes from baseline to end-point in fasting serum gastrin were comparable. No significant differences in laboratory parameters were seen.

Conclusion:

In this study, rabeprazole produced healing rates comparable to omeprazole at weeks 3 and 6, but provided more consistent and occasionally significantly superior symptom improvement. Both treatments were well-tolerated.