A randomized open-label trial of on-demand rabeprazole vs ranitidine for patients with non-erosive reflux disease

AIM: To compare the efficacy of the proton-pump inhibitor, rabeprazole, with that of the H₂-receptor antagonist, ranitidine, as on-demand therapy for relieving symptoms associated with non-erosive reflux disease (NERD).METHODS: This is a single center, prospective, randomized, open-label trial of on-demand therapy with rabeprazole (group A) vs ranitidine (group B) for 4 wk. Eighty-three patients who presented to the American University of Beirut Medical Center with persistent gastroesophageal reflux disease (GERD) symptoms and a normal upper gastrointestinal endoscopy were eligible for the study. Patients in group A (n = 44) were allowed a maximum rabeprazole dose of 20 mg twice daily, while those in group B (n = 39) were allowed a maximum ranitidine dose of 300 mg twice daily. Efficacy was assessed by patient evaluation of global symptom relief, scores of the SF-36 quality of life (QoL) questionnaires, total number of pills used, and number of medication-free days.RESULTS: Among the 83 patients who were enrolled in the study, 76 patients (40 in the rabeprazole group and 36 in the ranitidine group) completed the 4-wk trial. Baseline characteristics were comparable between both groups. After 4 wk, there was no significant difference in the subjective global symptom relief between the rabeprazole and the ranitidine groups (71.4% vs 65.4%, respectively; P = 0.9). There were no statistically significant differences between mean cumulative scores of the SF-36 QoL questionnaire for the two study groups (rabeprazole 22.40 ± 27.53 vs ranitidine 17.28 ± 37.06; P = 0.582). There was no significant difference in the mean number of pills used (rabeprazole 35.70 ± 29.75 vs ranitidine 32.86 ± 26.98; P = 0.66). There was also no statistically significant difference in the mean number of medication-free days between both groups.CONCLUSION: Rabeprazole has a comparable efficacy compared to ranitidine when given on-demand for the treatment of NERD. Both medications were associated with improved quality of life.     

The impact of body mass index on the application of on-demand therapy for Los Angeles grades A and B reflux esophagitis

BACKGROUND AND AIMS: Patients with Los Angeles grade A or B reflux esophagitis (RE-AB) can potentially be switched from active-phase therapy to on-demand esomeprazole as maintenance therapy. Body mass index (BMI) correlates significantly with reflux symptoms. We investigated whether BMI affects the efficacy of esomeprazole in active-phase or subsequent on-demand therapy. METHODS: Three hundred fifty patients with RE-AB were prospectively enrolled to receive an 8-wk course of esomeprazole (40 mg/day) as active-phase therapy. Based on the daily severity of acid regurgitation and heartburn, the cumulative proportions of patients with sustained symptomatic response (SSR), defined as free from symptoms for the last 7 days, were compared among different BMI groups (control: BMI <25 kg/m2, overweight: BMI 25-30 kg/m2, obese: BMI >30 kg/m2). In patients who had achieved SSR by week 8, on-demand therapy for 2 months was started. The number of 40-mg esomeprazole tablets used per 4-wk period was recorded. RESULTS: SSR rates were lower in both the overweight and obese groups than in the control group (P < 0.001). During on-demand therapy, the mean number of tablets used per 4-wk period was lower in the control group than in either the overweight or the obese group (13.2 vs 15.3 or 16.2, P < 0.05). The failure rate of on-demand therapy increased with increasing BMI-2.4%, 5.3%, and 14.2%, respectively, for the control, overweight, and obese groups (P= 0.002). CONCLUSION: For RE-AB, a higher BMI decreases the rate of SSR after 8-wk of esomeprazole therapy, and increases the need for medication and the failure rate of on-demand therapy.     

Esomeprazole 40 mg once a day in patients with functional dyspepsia: the randomized, placebo-controlled "ENTER" trial

OBJECTIVE: The etiologies of functional dyspepsia (FD) are unclear, but in some studies, treatment with a proton pump inhibitor has been beneficial. The objective of this study was to evaluate the efficacy of esomeprazole 40 mg once a day compared to placebo in achieving symptom relief in primary care patients with FD. METHODS: This was a randomized, placebo-controlled trial in adult FD patients, who had at least moderate severity of symptoms, defined as a score of > or =4 on a 7-point Global Overall Symptom (GOS) scale. Patients were excluded if they had predominant symptoms of heartburn or regurgitation; after a normal baseline endoscopy, patients were randomized to esomeprazole 40 mg once daily or placebo for 8 wk. The primary outcome measure was symptom relief (GOS < or =2) at 8 wk. RESULTS: Of the 502 enrolled patients, 224 were randomized. The main reasons for exclusion were abnormal endoscopic findings, especially esophagitis. A significantly greater proportion of patients in the esomeprazole group achieved symptom relief at 4 but not at 8 wk compared to placebo: 4 wk esomeprazole 50.5% versus placebo 32.2%, p= 0.009; 8 wk esomeprazole 55.1% versus placebo 46.1%, p= 0.16. A similar relationship at 4 and 8 wk was seen for symptom resolution (GOS = 1) and improvement (DeltaGOS > or =2). CONCLUSION: For the primary outcome measure of symptom relief at 8 wk, there was no statistically significant difference between esomeprazole 40 mg once a day and placebo. However, at 4 wk, esomeprazole was significantly more effective than placebo for symptom relief. The difference in therapeutic gain between 4 and 8 wk was largely due to a higher placebo response rate at 8 wk.     

Treatment of functional dyspepsia with sertraline: A double-blind randomized placebo-controlled pilot study

AIM:To evaluate sertraline,a selective serotonin reuptake inhibitor in the treatment of patients with functional dyspepsia.METHODS:Consecutive tertiary hospital patients with a clinical diagnosis of functional dyspepsia(FD) according to the Rome Ⅱ criteria with a Hong Kong dyspepsia index(HKDI) of greater than 16 were recruited.Patients commenced enrolment prior to the inception of the Rome Ⅲ criteria for functional dyspepsia.All patients were ethnic Chinese,had a normal upper endoscopy and were Helicobacter pylori negative prior to enrolment.Study patients were randomized to receive sertraline 50 mg or placebo daily for 8 wk.HKDI symptom scores,quality of life,hospital anxiety and depression(HAD) scale and global symptom relief were evaluated before,during and after treatment.Adverse effects were monitored during and after treatment.RESULTS:A total of 193 patients were randomized in the intention to treat(ITT),and 150 patients were included in the per protocol(PP) analysis.In both the ITT and PP,there was no difference in the primary outcome of global dyspepsia symptoms between the sertraline and placebo groups at week 8.In the ITT analysis,98 and 95 patients were randomized to the sertraline and placebo groups respectively.A total of 43 patients withdrew from the study(22.3%) by week 8,with 23 of the 24 drop-outs in the sertraline group occurring prior to week 4(95.8%).In contrast,in the placebo arm,11 of 19 patients dropped out by week 4(57.9%).Utilizing the last response carried forward to account for the drop-outs,there were no differences between the sertraline and placebo groups at baseline in terms of the HKDI,HKDI 26.08 ± 6.19 vs 26.70 ± 5.89,P = 0.433;and at week 8,HKDI 22.41 ± 6.36 vs 23.25 ± 7.30,P = 0.352 respectively.In the PP analysis,74 and 76 patients were randomized to the sertraline and placebo groups respectively.At baseline,there were no statistically significant differences between the sertraline and placebo groups,HKDI 25.83 ± 6.313 vs 27.19 ± 5.929 respectively,P = 0.233;however by week 8,patients in the sertraline group demonstrated a statistically significant difference in their Hong Kong Dyspepsia Index compared to placebo,HKDI 20.53 ± 6.917 vs 23.34 ± 7.199,P = 0.02,respectively).There was also no statistically significant difference in overall quality of life measures or the HAD scale related to treatment in either the ITT or PP analysis at week 8.CONCLUSION:This pilot study,the first to examine sertraline,a selective serotonin reuptake inhibitor,for the management of FD,did not find that it was superior to placebo.     

Low efficacy of levofloxacin-doxycycline-based third-line triple therapy for Helicobacter pylori eradication in Italy

AIM: To evaluate a levofloxacin-doxycycline-based triple therapy with or without a susceptibility culture test in non-responders to Helicobacter pylori (H. pylori) eradication.METHODS: A total of 142 (99 women, 43 men; mean 53.0 ± 12.7 years) non-responders to more than two H. pylori eradication therapies underwent susceptibility culture tests or were treated with a seven-day triple therapy consisting of esomeprazole, 20 mg b.i.d., levofloxacin, 500 mg b.i.d., and doxycycline, 100 mg b.i.d., randomly associated with (n = 71) or without (n = 71) Lactobacillus casei DG. H. pylori status was checked in all patients at enrollment and at least 8 wk after the end of therapy. Compliance and tolerability of regimens were also assessed.RESULTS: H. pylori eradication was achieved in < 50% of patients [per prototol (PP) = 49%; intention to treat (ITT) = 46%]. Eradication rate was higher in patients administered probiotics than in those without (PP = 55% vs 43%; ITT = 54% vs 40%). Estimated primary resistance to levofloxacin was 18% and multiple resistance was 31%. Therapy was well tolerated, and side effects were generally mild, with only one patient experiencing severe effects.CONCLUSION: Third-line levofloxacin-doxycycline triple therapy had a low H. pylori eradication efficacy, though the success and tolerability of this treatment may be enhanced with probiotics.     

A randomized trial comparing omeprazole, ranitidine, cisapride, or placebo in helicobacter pylori negative, primary care patients with dyspepsia: the CADET-HN Study

BACKGROUND: The management of Helicobacter pylori negative patients with dyspepsia in primary care has not been studied in placebo-controlled studies. METHODS: H. pylori negative patients with dyspepsia symptoms of at least moderate severity (> or =4 on a seven-point Likert scale) were recruited from 35 centers. Patients were randomized to a 4-wk treatment of omeprazole 20 mg od, ranitidine 150 mg bid, cisapride 20 mg bid, or placebo, followed by on-demand therapy for an additional 5 months. Treatment success was defined as no or minimal symptoms (score < or = 2 out of 7), and was assessed after 4 wk and at 6 months. RESULTS: Five hundred and twelve patients were randomized and included in the intention-to-treat (ITT) analysis. At 4 wk, success rates (95% CI) were: omeprazole 51% (69/135; 43-60%), ranitidine 36% (50/139, 28-44%), cisapride 31% (32/105, 22-39%), and placebo 23% (31/133, 16-31%). Omeprazole was significantly better than all other treatments (p < 0.05). The proportion of patients who were responders at 4 wk and at 6 months was significantly greater for those receiving omeprazole 31% (42/135, 23-39%) compared with cisapride 13% (14/105, 7-20%), and placebo 14% (18/133, 8-20%) (p= 0.001), but not ranitidine 21% (29/139, 14-27%) (p= 0.053). The mean number of on-demand study tablets consumed and rescue antacid used was comparable across groups. Economic analysis showed a trade-off between superior efficacy and increased cost between omeprazole and ranitidine. CONCLUSION: Treatment with omeprazole provides superior symptom relief compared to ranitidine, cisapride, and placebo in the treatment of H. pylori negative primary care dyspepsia patients.     

Comparative study of omeprazole, lansoprazole, pantoprazole and esomeprazole for symptom relief in patients with reflux esophagitis

AIM： To clarify whether there is any difference in the symptom relief in patients with reflux esophagitis following the administration of four Proton pump inhibitors （PPIs）. METHODS： Two hundred and seventy-four patients with erosive reflux esophagitis were randomized to receive 8 wk of 20 mg omeprazole （n = 68）, 30 mg of lansoprazole （n = 69）, 40 mg of pantoprazole （n = 69）, 40 mg of esomeprazole （n = 68） once a day in the morning. Daily changes in heartburn and acid reflux symptoms in the first 7 d of administration were assessed using a six-point scale （0： none; 1： mild; 2： mild-moderate; 3： moderate; 4： moderate-severe; 5： severe）. RESULTS： The mean heartburn score in patients treated with esomeprazole more rapidly decreased than those receiving other PPI. Complete resolution of heartburn was also more rapid in patients treated with esomeprazole for 5 d compared with omeprazole （P = 0.0018, P = 0.0098, P = 0.0027, P = 0.0137, P = 0.0069, respectively）, lansoprazole （P = 0.0020, P = 0.0046, P = 0.0037, P = 0.0016, P = 0.0076, respectively）, and pantoprazole （P = 0.0006, P = 0.0005, P = 0.0009, P = 0.0031, P = 0.0119, respectively）. There were no significant differences between the four groups in the rate of endoscopic healing of reflux esophagitis at week 8. CONCLUSION： Esomeprazole may be more effective than omeprazole, lansoprazole, and pantoprazole for the rapid relief of heartburn symptoms and acid reflux symptoms in patients with reflux esophagitis.     

Comparative study of esomeprazole and lansoprazole in triple therapy for eradication of Helicobacter pylori in Japan

AIM:To evaluate the efficacy and safety of esomeprazole-based triple therapy compared with lansoprazole therapy as first-line eradication therapy for patients with Helicobacter pylori(H.pylori)in usual post-marketing use in Japan,where the clarithromycin(CAM)resistance rate is 30%.METHODS:For this multicenter,randomized,openlabel,non-inferiority trial,we recruited patients(≥20years of age)with H.pylori infection from 20 hospitals in Japan.We randomly allocated patients to esomeprazole therapy(esomeprazole 20 mg,CAM 400 mg,amoxicillin(AC)750 mg for the first 7 d,with all drugs given twice daily)or lansoprazole therapy(lansoprazole30 mg,CAM 400 mg,AC 750 mg for the first 7 d,with all drugs given twice daily)using a minimization method with age,sex,and institution as adjustment factors.Our primary outcome was the eradication rate by intention-to-treat(ITT)and per-protocol(PP)analyses.H.pylori eradication was confirmed by a urea breath test from 4 to 8 wk after cessation of therapy.RESULTS:ITT analysis revealed the eradication rates of 69.4%(95%CI:61.2%-76.6%)for esomeprazole therapy and 73.9%(95%CI:65.9%-80.6%)for lansoprazole therapy(P=0.4982).PP analysis showed eradication rate of 76.9%(95%CI:68.6%-83.5%)for esomeprazole therapy and 79.8%(95%CI:71.9%-86.0%)for lansoprazole therapy(P=0.6423).There were no differences in adverse effects between the two therapies.CONCLUSION:Esomeprazole showed non-inferiority and safety in a 7 day-triple therapy for eradication of H.pylori compared with lansoprazole.     

40 mg pantoprazole and 40 mg esomeprazole are equivalent in the healing of esophageal lesions and relief from gastroesophageal reflux disease-related symptoms

BACKGROUND: Proton pump inhibitors are regarded as the most effective class of acid suppressive medication for gastroesophageal reflux disease treatment. There is considerable interest regarding the dose equivalence between various proton pump inhibitors. GOALS: To compare the efficacy of pantoprazole and esomeprazole with regard to healing and relief from gastroesophageal reflux disease-related symptoms. STUDY: Multicenter, randomized, double-blind study. Patients with gastroesophageal reflux disease grades B/C (Los Angeles classification) received 40 mg pantoprazole daily (n = 113) or 40 mg esomeprazole daily (n = 114). Healing (endoscopy) and relief from gastroesophageal reflux disease-related symptoms (direct questioning) were assessed at first and final visit (after 4, 6, 8, or 10 weeks of treatment). RESULTS: Overall healing in both treatment groups was 88% of patients (intention-to-treat population), 95% (pantoprazole), and 90% (esomeprazole) (per-protocol population); statistically, this indicates "at least equivalence" between treatments. Overall relief from gastroesophageal reflux disease-related symptoms was similar for pantoprazole (55%) and esomeprazole (51%, per-protoco). No correlation between healing and symptom relief was seen. The majority of reported adverse events were assessed as "not related" to the study drug. Pantoprazole and esomeprazole have comparably good safety and tolerability. CONCLUSION: In patients with gastroesophageal reflux disease, 40 mg pantoprazole daily and 40 mg esomeprazole daily are equally effective for healing of esophageal lesions and relieving gastroesophageal reflux disease-related symptoms.     

Efficacy of treatment with rebamipide for endoscopic submucosal dissection-induced ulcers

AIM:To prospectively compare the healing rates of endoscopic submucosal dissection(ESD)-induced ulcers treated with either a proton-pump inhibitor(PPI)or rebamipide.METHODS:We examined 90 patients with early gastric cancer who had undergone ESD.All patients were administered an intravenous infusion of the PPI lansoprazole(20 mg)every 12 h for 2 d,followed by oral administration of lansoprazole(30 mg/d,5 d).After7-d treatment,the patients were randomly assigned to 2 groups and received either lansoprazole(30 mg/d orally,n=45;PPI group)or rebamipide(300 mg orally,three times a day;n=45;rebamipide group).At 4and 8 wk after ESD,the ulcer outcomes in the 2 groups were compared.RESULTS:No significant differences were noted in patient age,underlying disease,tumor location,Helicobacter pylori infection rate,or ESD-induced ulcersize between the 2 groups.At both 4 and 8 wk,the healing rates of ESD-induced ulcers were similar in the PPI-treated and the rebamipide-treated patients(4 wk:PPI,27.2%;rebamipide,33.3%;P=0.5341;8 wk:PPI,90.9%;rebamipide,93.3%;P=0.6710).At 8 wk,the rates of granulation lesions following ulcer healing were significantly higher in the PPI-treated group(13.6%)than in the rebamipide-treated group(0.0%;P=0.0103).Ulcer-related symptoms were similar in the2 treatment groups at 8 wk.The medication cost of 8-wk treatment with the PPI was 10945 yen vs 4889 yen for rebamipide.No ulcer bleeding or complications due to the drugs were observed in either treatment group.CONCLUSION:The healing rate of ESD-induced ulcers was similar with rebamipide or PPI treatment;however,rebamipide treatment is more cost-effective and prevents granulation lesions following ulcer healing.     

Alanine aminotransferase normalization at week 8 predicts viral response during hepatitis C treatment

AIM:To investigate alanine aminotransferase(ALT)and sustained virological response(SVR)in chronic hepatitis C(CHC)during peginterferon-ribavirin treatment.METHODS:One hundred and fifty-one genotype 1CHC patients underwent treatment for 48 wk with peginterferon and ribavirin,and were retrospectively divided into two groups as having a rapid virological response(RVR)(Group 1,n=52)and not having an RVR(Group 2,n=99).We also subdivided each group into two according to the initial ALT level being high(Group1h and Group 2h)or normal(Group 1n and Group 2n).HCV RNA and ALT levels were measured at baseline;at 4,12,24 and 48 wk during the treatment period;and at 24 wk follow-up.ALT levels were also obtained at 8 wk.According to the results of ALT,patients were enrolled in either the follow-up abnormal or follow-up normalized ALT groups at each interval.Patients with high and normal ALT levels were compared for each interval in terms of SVR.RESULTS:The SVR rates were 83%vs 40%(P=0.000),82%vs 84%(P=0.830),and 37%vs 44%(P=0.466)when comparing Group 1 with 2,1h with1n,and 2h with 2n,respectively.In Group 2h,the SVR rates were 34%vs 40%(P=0.701),11%vs 52%(P=0.004),12%vs 50%(P=0.007),7%vs 50%(P=0.003),6%vs 53%(P=0.001),and 0%vs 64%(P=0.000)when comparing patients with high and normalized ALT levels at week 4,8,12,24,48 and 72,respectively.The multiple logistic regression analysis revealed that RVR(OR=7.05;95%CI:3.1-16.05,P=0.000),complete early virological response(cEVR)(OR=17.55;95%CI:6.32-48.76,P=0.000),normalization of ALT at8 wk(OR=3.04;95%CI:1.31-7.06,P=0.008),and at 12 wk(OR=4.21;95%CI:1.65-10.76,P=0.002)were identified as independent significant predictive factors for SVR.CONCLUSION:Normalization of ALT at 8 wk may predict viral response during peginterferon-ribavirin treatment in genotype-1 CHC patients especially without RVR.     

Treatment of Reflux Esophagitis Resistant to H2-Receptor Antagonists with Lansoprazole, a New H+/K+-ATPase Inhibitor: A Controlled, Double-Blind Study

This multicenter, randomized, double-blind, 8-wk study compared the new H⁺/K⁺-ATPase inhibitor, lansoprazole, 30 mg daily, to ranitidine 150 mg bid for treatment of erosive reflux esophagitis resistant to his-tamine-2 receptor antagonists (H2RA). Patients were evaluated after 2, 4, 6, and 8 wk of treatment by symptom assessment and endoscopy. Healing rates for lansoprazole were 71%, 80%, 88%, and 89% at 2, 4, 6, and 8 wk, respectively, compared to 21%, 33%, 45%, and 38% for ranitidine ( p < 0.001 at all points). Lansoprazole was significantly more effective than ranitidine for relief of heartburn and reduction of antacid tablet use. Increases in serum gastrin concentrations between the baseline and the 8-wk visit were greater in lansoprazole-treated than in ranitidine treated patients. Lansoprazole was safe and well tolerated. In patients with erosive reflux esophagitis resistant to standard doses of H2RA, lansoprazole 30 mg/day is more effective than continuation of an H2RA (ranitidine 150 mg bid) for healing of esophagitis and improvement of symptoms.     

Interval to surgery after neoadjuvant treatment for colorectal cancer

The current standard treatment of low-lying locally advanced rectal cancer consists of chemoradiation followed by radical surgery.The interval between chemoradiation and surgery varied for many years until the1999 Lyon R90-01 trial which compared the effects of a short(2-wk)and long(6-wk)interval.Results showed a better clinical tumor response(71.7%vs 53.1%)and higher rate of positive and pathologic tumor regression(26%vs 10.3%)after the longer interval.Accordingly,a 6-wk interval between chemoradiation and surgery was set to balance the oncological results with the surgical complexity.However,several recent retrospective studies reported that prolonging the interval beyond 8or even 12 wk may lead to significantly higher rates of tumor downstaging and pathologic complete response.This in turn,according to some reports,may improve overall and disease-free survival,without increasing the surgical difficulty or complications.This work reviews the data on the effect of different intervals,derived mostly from retrospective analyses using a wide variation of treatment protocols.Prospective randomized trials are currently ongoing.     

Double-Blind, Placebo-Controlled Trial with Single-Dose Pantoprazole for Laryngopharyngeal Reflux CME

OBJECTIVES: Results of randomized treatment trials for laryngopharyngeal reflux (LPR) are mixed. The cause and effect between gastroesophageal reflux and laryngeal symptoms remain elusive.
AIMS: To determine the efficacy of single-dose pantoprazole in newly diagnosed LPR and to correlate hypopharyngeal reflux with symptom improvement.
METHODS: Randomized, double-blind, placebo-controlled trial was performed with a 2-wk run-in, 12-wk treatment period (pantoprazole 40 mg q.a.m. or placebo), and 4-wk follow-up. Study criteria were laryngeal complaints >3 days/wk and a positive triple-sensor pH test. Laryngeal exam was graded using a reflux finding score before and after treatment. Repeat pH test was performed on study drug at week 12. Weekly diaries were kept on symptom severity and global assessment. Total laryngeal symptom score was defined as the sum of six laryngeal symptoms. Mann-Whitney U, Wilcoxon, and Pearson tests were used.
RESULTS: Thirty-nine subjects (13 M/26 F, median age 39 yr) were randomized; 35 completed the study. During the treatment period, total laryngeal symptom scores significantly improved compared with pretreatment scores in both study groups, but there were no significant differences between them. Forty percent of pantoprazole group reported adequate relief at week 12, compared with 42% of placebo group ( p = 0.89). No significant improvement in hypopharyngeal reflux was found in either study group. There were no significant correlations between laryngeal reflux finding scores and hypopharyngeal reflux episodes with symptom improvement.
CONCLUSIONS: Response was similar between single-dose pantoprazole and placebo in newly diagnosed LPR. Our results suggested that laryngeal exam was not useful in following treatment response. Hypopharyngeal reflux may represent acid reflux or artifacts, but is not likely the underlying cause.     

Randomized study of lafutidine vs lansoprazole in patients with mild gastroesophageal reflux disease

AIM: To compare the clinical efficacy of the second-generation H2RA lafutidine with that of lansoprazole in Japanese patients with mild gastroesophageal reflux disease (GERD).METHODS: Patients with symptoms of GERD and a diagnosis of grade A reflux esophagitis (according to the Los Angeles classification) were randomized to receive lafutidine (10 mg, twice daily) or lansoprazole (30 mg, once daily) for an initial 8 wk, followed by maintenance treatment comprising half-doses of the assigned drug for 24 wk. The primary endpoint was the frequency and severity of heartburn during initial and maintenance treatment. The secondary endpoints were the sum score of questions 2 and 3 in the Gastrointestinal Symptom Rating Scale (GSRS), and the satisfaction score.RESULTS: Between April 2012 and March 2013, a total of 53 patients were enrolled, of whom 24 and 29 received lafutidine and lansoprazole, respectively. After 8 wk, the frequency and severity of heartburn was significantly reduced in both groups. However, lafutidine was significantly inferior to lansoprazole with regard to the severity of heartburn during initial and maintenance treatment (P = 0.016). The sum score of questions 2 and 3 in the GSRS, and satisfaction scores were also significantly worse in the lafutidine group than the lansoprazole group (P = 0.0068 and P = 0.0048, respectively).CONCLUSION: The clinical efficacy of lafutidine was inferior to that of lansoprazole, even in Japanese patients with mild GERD.     

Clinical trial: Lactobacillus plantarum 299v (DSM 9843) improves symptoms of irritable bowel syndrome

AIM: To assess the symptomatic efficacy of Lactobacillus plantarum 299v (L. plantarum 299v) (DSM 9843) for the relief of abdominal symptoms in a large subset of irritable bowel syndrome (IBS) patients fulfilling the Rome III criteria.METHODS: In this double blind, placebo-controlled, parallel-designed study, subjects were randomized to daily receive either one capsule of L. plantarum 299v (DSM 9843) or placebo for 4 wk. Frequency and intensity of abdominal pain, bloating and feeling of incomplete rectal emptying were assessed weekly on a visual analogue scale while stool frequency was calculated.RESULTS: Two hundred and fourteen IBS patients were recruited. After 4 wk, both pain severity (0.68 + 0.53 vs 0.92 + 0.57, P < 0.05) and daily frequency (1.01 + 0.77 vs 1.71 + 0.93, P < 0.05) were lower with L. plantarum 299v (DSM 9843) than with placebo. Similar results were obtained for bloating. At week 4, 78.1 % of the patients scored the L. plantarum 299v (DSM 9843) symptomatic effect as excellent or good vs only 8.1 % for placebo (P < 0.01).CONCLUSION: A 4-wk treatment with L. plantarum 299v (DSM 9843) provided effective symptom relief, particularly of abdominal pain and bloating, in IBS patients fulfilling the Rome III criteria.     

Esomeprazole versus other proton pump inhibitors in erosive esophagitis: a meta-analysis of randomized clinical trials.

BACKGROUND & AIMS: There are limited data comparing the effectiveness of available proton pump inhibitors (PPIs) in erosive esophagitis (EE). We performed a meta-analysis to calculate the pooled effect of esomeprazole on healing rates, symptom relief, and adverse events versus competing PPIs in EE. METHODS: We performed a structured electronic search of MEDLINE and EMBASE and reviewed published abstracts to identify English-language, randomized clinical trials from 1995-2005, comparing rates of endoscopic healing, symptom relief, and adverse events with esomeprazole versus alternative PPIs in the treatment of gastroesophageal reflux disease (GERD)/EE. We then performed meta-analysis to compare the relative risk (RR) of EE healing, symptom relief, and adverse events between study arms and calculated the absolute risk reduction and number needed to treat (NNT) for each outcome. RESULTS: Meta-analysis was performed on 10 studies (n=15,316). At 8 weeks, there was a 5% (RR, 1.05; 95% confidence interval, 1.02-1.08) relative increase in the probability of healing of EE with esomeprazole, yielding an absolute risk reduction of 4% and NNT of 25. The calculated NNTs by Los Angeles grade of EE (grades A-D) were 50, 33, 14, and 8, respectively. Last, esomeprazole conferred an 8% (RR, 1.08; 95% confidence interval, 1.05-1.11) relative increase in the probability of GERD symptom relief at 4 weeks. CONCLUSIONS: As compared with other PPIs, esomeprazole confers a statistically significant improvement, yet, clinically, only a modest overall benefit in 8-week healing and symptom relief in all-comers with EE. The clinical benefit of esomeprazole appears negligible in less severe erosive disease but might be important in more severe disease.     

Double-blind, placebo-controlled trial with single-dose pantoprazole for laryngopharyngeal reflux

OBJECTIVES: Results of randomized treatment trials for laryngopharyngeal reflux (LPR) are mixed. The cause and effect between gastroesophageal reflux and laryngeal symptoms remain elusive. AIMS: To determine the efficacy of single-dose pantoprazole in newly diagnosed LPR and to correlate hypopharyngeal reflux with symptom improvement. METHODS: Randomized, double-blind, placebo-controlled trial was performed with a 2-wk run-in, 12-wk treatment period (pantoprazole 40 mg q.a.m. or placebo), and 4-wk follow-up. Study criteria were laryngeal complaints >3 days/wk and a positive triple-sensor pH test. Laryngeal exam was graded using a reflux finding score before and after treatment. Repeat pH test was performed on study drug at week 12. Weekly diaries were kept on symptom severity and global assessment. Total laryngeal symptom score was defined as the sum of six laryngeal symptoms. Mann-Whitney U, Wilcoxon, and Pearson tests were used. RESULTS: Thirty-nine subjects (13 M/26 F, median age 39 yr) were randomized; 35 completed the study. During the treatment period, total laryngeal symptom scores significantly improved compared with pretreatment scores in both study groups, but there were no significant differences between them. Forty percent of pantoprazole group reported adequate relief at week 12, compared with 42% of placebo group (p= 0.89). No significant improvement in hypopharyngeal reflux was found in either study group. There were no significant correlations between laryngeal reflux finding scores and hypopharyngeal reflux episodes with symptom improvement. CONCLUSIONS: Response was similar between single-dose pantoprazole and placebo in newly diagnosed LPR. Our results suggested that laryngeal exam was not useful in following treatment response. Hypopharyngeal reflux may represent acid reflux or artifacts, but is not likely the underlying cause.     

Efficacy and safety profile of LCR35 complete freeze-dried culture in irritable bowel syndrome: a randomized, double-blind study

AIM: To assess the effects and safety of Lactobacillus casei rhamnosus LCR35 complete freeze-dried culture (LCR35) in patients suffering from irritable bowel syndrome (IBS).METHODS: A randomized, double-blind pilot study was performed in 50 patients complaining of IBS symptoms complying with Rome III criteria. Patients were allocated to receive either LCR35 (n = 25) at a minimum daily dose of 6 × 10⁸ colony forming units or placebo (n = 25) for 4 wk. At inclusion, after treatment and 2 wk later, patients completed the IBS severity scale. Change from baseline in the IBS severity score at the end of treatment was the primary efficacy criterion. Changes were compared between groups in the whole population and in IBS subtypes (IBS with predominance of constipation, IBS with predominance of diarrhoea, mixed IBS, unsubtyped IBS). The presence of lactobacillus casei rhamnosus in stools was investigated at inclusion and at the end of treatment. The gastrointestinal quality of life questionnaire and the hospital anxiety and depression (HAD) scale were also completed.RESULTS: Both groups were balanced for baseline characteristics. In 85% of patients, stool analyses showed that lactobacillus casei rhamnosus able to survive in the digestive tract. In the whole population, improvements in the IBS severity score did not differ significantly between treatments with a 25% decrease after 4-wk treatment, and a 15% decrease from baseline 2 wk later in both groups. In IBS subgroups, statistical analysis could not be performed due to small sample size, but a clinical response in favour of LCR35 was observed in IBS patients with predominance of diarrhoea: no change in the symptom severity score was seen with the placebo after 4 wk treatment, whereas a clinically relevant decrease occurred with LCR35 (-37% vs -3%). Furthermore, in spite of an increase in symptom intensity, the IBS severity score was maintained below the baseline value 2 wk later with LCR35 (-19% from baseline), whilst a slight 5% increase from baseline was observed with placebo. In the IBS subgroup with predominance of diarrhoea only, a clinically relevant decrease in abdominal pain severity score (-36%) was observed with LCR35, whereas no change occurred with placebo. In mixed IBS patients, the 20% and 30% decreases in the IBS severity score observed after treatment with LCR35 and placebo, respectively, were maintained 2 wk later in both groups. A clinical response slightly in favour of placebo was observed at the end of the treatment period in IBS patients with predominance of constipation (-41% vs -20%) and unsubtyped IBS patients (-47% vs -17%), with the same value maintained 2 wk later. In both groups, no clinically relevant changes were observed either for the gastrointestinal quality of life index or HAD score. Thus, these results suggest that sub-grouping of IBS patients may be important for optimizing treatment responses by the physician.CONCLUSION: This pilot study suggests that LCR35 could have some efficacy in IBS patients complaining of diarrhoea. These preliminary results need to be confirmed in larger studies.     

Esomeprazole 40 mg and 20 mg is efficacious in the long-term management of patients with endoscopy-negative gastro-oesophageal reflux disease: a placebo-controlled trial of on-demand therapy for 6 months

BACKGROUND: On-demand therapy may offer an effective approach to the long-term management of gastro-oesophageal reflux disease (GORD) without oesophagitis. AIM: To examine the efficacy of the novel proton pump inhibitor esomeprazole as on-demand therapy in endoscopy-negative GORD. PATIENTS AND METHODS: Endoscopy-negative GORD patients who achieved complete resolution of heartburn after short-term esomeprazole or omeprazole treatment (n = 721) were randomized to esomeprazole 20 mg (n = 282), 40 mg (n = 293) or placebo (n = 146) on demand (maximum one dose/day) for 6 months. The primary and secondary efficacy endpoints were time to study discontinuation due to (i) unwillingness to continue and (ii) inadequate control of heartburn, respectively. RESULTS: Both doses of esomeprazole were more effective than placebo. During the 6-month period, 42% of placebo recipients discontinued treatment due to unwillingness to continue, compared with 8% and 11% of esomeprazole 20 mg and 40 mg recipients, respectively. Overall, more patients treated with esomeprazole were free from gastrointestinal symptoms after 6 months of on-demand therapy. CONCLUSIONS: Esomeprazole 20 mg was superior to placebo for on-demand treatment of GORD; a higher dose did not confer additional clinical benefit. Over 90% of patients were willing to continue on-demand treatment with esomeprazole 20 mg over a 6-month period.