One-week acid suppression trial in uninvestigated dyspepsia patients with epigastric pain or burning to predict response to 8 weeks' treatment with esomeprazole: a randomized, placebo-controlled study.

BACKGROUND: While empiric acid-suppressive therapy for uninvestigated dyspepsia patients with symptoms of epigastric pain or burning is standard practice, it is unknown whether an early response to therapy predicts outcome. AIM: To evaluate whether a 1-w acid suppression trial is effective for predicting 8-w response in such patients. METHODS: Helicobacter pylori-negative patients (aged 18-50 years) in primary care with uninvestigated epigastric pain or burning were randomized to esomeprazole 40 mg q.d.s. or b.d. for 1w, followed by esomeprazole 40 mg q.d.s. or placebo for 7w. Each day, patients rated the severity of their symptoms. RESULTS: Based on the last 3d, 1-w response rates were 39% (231 of 588) and 43% (258 of 596) with esomeprazole 40 mg q.d.s. and b.d., respectively. Based on the last 7d, response rates at 4w were 38% (283 of 738) and 25% (93 of 380) for esomeprazole and placebo, respectively, and 47% (339 of 716) and 34% (124 of 368), respectively, at 8w (both P < 0.001 vs. placebo). The sensitivity and specificity of esomeprazole treatment were 58% and 70%, respectively, at 8w. CONCLUSION: A 1-w acid suppression trial is of limited clinical value for predicting 8-w response in patients with symptoms of epigastric pain or burning. Esomeprazole provides greater symptom control than placebo at 4w and 8w.

Randomized-controlled trial of esomeprazole in functional dyspepsia patients with epigastric pain or burning: does a 1-week trial of acid suppression predict symptom response?

BACKGROUND: Early identification of true responders to acid suppression in functional dyspepsia patients with symptoms of epigastric pain or burning may enable clinicians to optimally tailor treatment. AIM: To evaluate whether a 1-w acid suppression trial is useful for identifying true responders in this population. METHODS: Patients (18-70 years) were randomized to either esomeprazole 40 mg q.d.s., b.d. or placebo for 1w, and then esomeprazole 40 mg q.d.s. or placebo for 7w. Epigastric pain and/or burning were recorded on a 4-point scale (0 = none, 3 = severe). Trial-week response was defined as symptom score sum < or = 1 on last 3d of therapy; response at 8w was symptom score sum < or = 1 over preceding 7d. RESULTS: 1-w response rates were 33% (199 of 597), 29% (188 of 629) and 23% (71 of 315) with esomeprazole q.d.s., esomeprazole b.d. and placebo, respectively (P = 0.002 for esomeprazole groups vs. placebo). At 8w, trial week sensitivity and specificity were 46% and 80%, respectively, for esomeprazole (40 or 80 mg), and 33% and 87%, respectively, for placebo. The positive and negative predictive values for esomeprazole were 60% and 69%. CONCLUSION: Response to a 1-w acid suppression trial is of limited use for predicting symptom response at 8w in patients with unexplained epigastric pain or burning.

Transfer of maternal immunity to piglets is involved in early protection against Mycoplasma hyosynoviae infection.

Mycoplasma hyosynoviae causes arthritis in pigs older than 12 weeks. The role of colostrum in protection of piglets against M. hyosynoviae infection is not clear. Our objective was therefore to investigate whether transfer of maternal immunity to piglets was involved in early protection against the infection. Experimental infections were carried out in three groups of weaners receiving different levels of M. hyosynoviae-specific colostrum components; Group NC derived from Mycoplasma free sows and possessed no specific immunity to M. hyosynoviae. Group CAb pigs, siblings of the NC group, received colostrum with M. hyosynoviae-specific antibodies immediately after birth. Group CCE pigs were born and raised by infected sows and presumably had the full set of colostrally transferred factors, including specific antibodies. When 4½ weeks old, all pigs were inoculated intranasally with M. hyosynoviae. The course of infection was measured through clinical observations of lameness, cultivation of M. hyosynoviae from tonsils, blood and synovial fluid and observation for gross pathological lesions in selected joints. Specific immune status in the pigs was evaluated through detection of antibodies by immunoblotting and measurement of M. hyosynoviae-specific T-cell proliferation. The latter analysis may possibly indicate that M. hyosynoviae infection induces a T-cell response. The CCE piglets were significantly protected against development of lameness and pathology, as well as infection with M. hyosynoviae in tonsils, blood and joints, when compared to the two other groups. Raising the CCE pigs in an infected environment until weaning, with carrier sows as mothers, apparently made them resistant to M. hyosynoviae-arthritis when challenge-infected at 4½ weeks of age. More pigs in group NC had M. hyosynoviae related pathological lesions than in group CAb, a difference that was significant for cubital joints when analysed on joint type level. This finding indicates a partially protective effect of passively transferred M. hyosynoviae-specific colostral antibodies upon development of M. hyosynoviae related pathology. Thus, the level of passive immunity transferred from sow to piglet seems to provide, at least partial, protection against development of arthritis. It cannot be ruled out that the CCE pigs, by growing up in an infected environment, have had the chance to establish an active anti-M. hyosynoviae immune response that complements the maternally transferred immune factors. Evident from this study is that the general absence of M. hyosynoviae arthritis in piglets can be ascribed mainly to their immunological status.

Gastrointestinal insulinotropic hormones in normal and gestational-diabetic pregnancy: response to oral glucose.

The responses of gastric inhibitory polypeptides (GIP), gut glucagon-like-immunoreactivity (gut GLI), insulin, and pancreatic glucagon to a 50-g oral glucose load were studied in late pregnancy and postpartum in 11 normal women, 10 normal weight gestational diabetics, and 10 overweight gestational diabetics. The GIP response to glucose was impaired in pregnancy in all three groups. In pregnancy, the GIP response was smaller in both groups of gestational diabetics than in normal women, whereas postpartum, the GIP response was lower than normal in the normal weight gestational diabetics only. In pregnancy, the gut GLI response to glucose was reduced in the overweight gestational diabetics and abolished in the normal women. The insulin response to glucose was increased in pregnancy in all three groups. Moreover, it was higher in the overweight gestational diabetics than in the other two groups in pregnancy and postpartum. In the normals, the suppression of glucagon levels after glucose ingestion was more marked in pregnancy than postpartum, whereas no such effect was seen in gestational-diabetic pregnancy. It is concluded that pregnancy--normal as well as gestational-diabetic--is accompanied by profound changes in the secretion of gastrointestinal insulinotropic hormones after glucose ingestion. These findings may be important for the understanding of changes in metabolism and gastrointestinal physiology in gestation.

A randomized comparative study of esomeprazole 40 mg versus pantoprazole 40 mg for healing erosive oesophagitis: the EXPO study.

AIM: To assess the efficacy of the 8-week therapy with esomeprazole 40 mg vs. pantoprazole 40 mg for healing erosive oesophagitis (EE) as part of a management study. METHODS: Patients had a history of gastro-oesophageal reflux disease symptoms (> or =6 months) and had suffered heartburn on at least 4 of the 7 days preceding enrollment. Endoscopies were performed to grade EE severity using the Los Angeles (LA) classification system at baseline, 4 and 8 weeks (if unhealed at 4 weeks). Heartburn severity was recorded by patients on diary cards. The primary end point was healing of EE by week 8 of treatment. RESULTS: Of 3170 patients randomized, the intent-to-treat population consisted of 3151 patients (63% male, mean age: 50.6 years, 27% Helicobacter pylori-positive). Esomeprazole 40 mg healed a significantly greater proportion of EE patients than pantoprazole 40 mg at both 4 weeks (life table estimates: esomeprazole 81%, pantoprazole 75%, P < 0.001) and 8 weeks (life table estimates: esomeprazole 96%, pantoprazole 92%, P < 0.001). The median time to reach sustained heartburn resolution was 6 days in patients receiving esomeprazole and 8 days with pantoprazole (P < 0.001). CONCLUSION: Esomeprazole 40 mg is more effective than pantoprazole 40 mg for healing EE and providing resolution of associated heartburn.

Esomeprazole 20 mg vs. pantoprazole 20 mg for maintenance therapy of healed erosive oesophagitis: results from the EXPO study.

BACKGROUND: Following initial healing of erosive oesophagitis, most patients require maintenance therapy to prevent relapse. AIM: To compare endoscopic and symptomatic remission rates over 6 months' maintenance therapy with esomeprazole or pantoprazole (both 20 mg once daily) in patients with healed erosive oesophagitis. METHODS: Patients with symptoms of gastro-oesophageal reflux disease and endoscopically confirmed erosive oesophagitis at baseline were randomized to receive esomeprazole 40 mg or pantoprazole 40 mg for up to 8 weeks. Patients with healed erosive oesophagitis and free of moderate/severe heartburn and acid regurgitation at 4 weeks or, if necessary, 8 weeks entered the 6-month maintenance therapy phase of the study. RESULTS: A total of 2766 patients (63% men; mean age 50 years) received esomeprazole 20 mg (n = 1377) or pantoprazole 20 mg (n = 1389) and comprised the intention-to-treat population. Following 6 months of treatment, the proportion of patients in endoscopic and symptomatic remission was significantly greater for those receiving esomeprazole 20 mg (87.0%) than pantoprazole 20 mg (74.9%, log-rank test P < 0.0001). Esomeprazole 20 mg produced a higher proportion of patients free of moderate to severe gastro-oesophageal reflux disease symptoms and fewer discontinuations because of symptoms than pantoprazole 20 mg (92.2% vs. 88.5%, P < 0.001). CONCLUSIONS: Esomeprazole 20 mg is more effective than pantoprazole 20 mg for maintenance therapy following initial healing of erosive oesophagitis and relief of gastro-oesophageal reflux disease symptoms.

Gastric inhibitory polypeptide and insulin: response to intraduodenal and intravenous glucose infusions in fetal and neonatal pigs.

The responses of gastric inhibitory polypeptide (GIP) and insulin to intraduodenal (OGTT) and iv (IVGI) glucose infusions were measured in 14 late fetal and 9 neonatal pigs. Basal plasma glucose (P < 0.01) and GIP (P < 0.001) concentrations were lower in the fetal than in the neonatal pigs, while basal plasma insulin was not significantly different in the two groups. In the fetal pigs, almost identical plasma glucose curves were obtained during the OGTT and the IVGI, but plasma insulin did not change during either test. In these pigs, plasma GIP increased 3-fold (P < 0.01) during the OGTT, whereas no significant changes in plasma GIP were observed during the IVGI. In the neonatal pigs, plasma glucose increased more during the OGTT than during the IVGI, but plasma insulin exhibited similar increments during both tests. Thus, the insulinogenic index of the IVGI was almost 3 times higher than that of the OGTT (P < 0.05). In contrast to the normal increment in plasma GIP observed in fetal pigs, plasma GIP decreased significantly during both tests in the neonatal pigs. It is concluded that beta-cells of fetal pigs are unresponsive to acute elevations of plasma glucose with or without a concomitant increase in plasma GIP. Conversely, beta-cells of neonatal pigs exhibit a significant response to hyperglycemia, but the enteroinsular axis is defective, since more insulin is released after iv than during intraduodenal glucose administration. The defective enteroinsular axis in neonatal pigs might be due to the observed fall in plasma GIP during the OGTT.

Diminished gastric inhibitory polypeptide response to oral glucose in late human pregnancy.

It has been shown that the incretin effect - i.e. the gastrointestinal potentiation of the insulin response to oral glucose - is reduced in late normal pregnancy. As evidence points to gastric inhibitory polypeptide (GIP) as mediator of at least part of the incretin effect, the GIP response was determined following a 50 g oral glucose load in 6 normal women in the last trimester of pregnancy and again post partum. Compared to post partum the GIP response to oral glucose was significantly impaired in late pregnancy. It is concluded that the diminished GIP response to oral glucose in late pregnancy might at least partly explain the impaired incretin effect found in this condition.

Blockade of leukotriene production by a single oral dose of MK-0591 in active ulcerative colitis.

BACKGROUND: 5-Lipoxygenase products of arachidonic acid metabolism are thought to play a central role in the secondary amplification of the inflammatory response in a number of human inflammatory diseases, such as ulcerative colitis. MK-0591 (3-(1((4-chlorophenyl)methyl)-3((1,1-dimethyl-ethyl)thio)-5(quinolin+ ++-2ylmethyl-oxy)-1H-indol-2yl)-2,2-dimethyl-propanoate) exerts its effect by binding to the 5-lipoxygenase activating protein, thereby inhibiting the translocation and activation of 5-lipoxygenase. METHODS: Concentrations of leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) in rectal dialysis fluid, ex vivo biosynthesis of LTB4 in whole blood, and urinary excretion of leukotriene E4 (LTE4) from 16 patients with mild to moderately active distally located ulcerative colitis were measured by use of radioimmunoassays in a double-blind, placebo-controlled parallel-design study before and after oral administration of a 250 mg dose of MK-0591 or placebo. RESULTS: The mean LTB4 concentration in rectal dialysis fluid was lowered after MK-0591 by > 90% (p < 0.05) from 4 to 8 hours, with a maximum inhibition of 97.5% +/- 3.4% (mean +/- SD) at 20 to 24 hours after dosing, whereas PGE2 was unchanged. In whole blood, MK-0591 decreased ex vivo biosynthesis of LTB4 (p < 0.01), with a maximum inhibition of 96.4% +/- 2.1% at 4 hours after dosing. Urinary excretion of LTE4 was reduced by more than 85% (p < 0.001) from 4 to 48 hours. No adverse events were observed. CONCLUSION: These findings show that a single oral 250 mg dose of MK-0591 results in nearly complete blockade of systemic leukotriene production and LTB4 formation in the target tissue of inflammation (the rectum). Controlled multiple-dose trials to assess the clinical efficacy of this novel 5-lipoxygenase-activating protein inhibitor seem to be worthwhile.

Clinical pharmacokinetics of drugs used in the treatment of gastrointestinal diseases (Part II).

Part I of this article, which appeared in the previous issue of the Journal, covered the following agents: histamine H2-receptor antagonists (cimetidine, ranitidine, famotidine, nizatidine); muscarinic-M1-receptor antagonists (pirenzepine); proton pump inhibitors (omeprazole); site-protective agents (colloidal bismuth subcitrate, sucralfate); antacids and prostaglandin analogues; antiemetics and prokinetics (metoclopramide, domperidone, cisapride); and antispasmodics. In Part II, we consider the anti-inflammatory salicylates, nonspecific antidiarrhoeal agents, laxatives and cathartics.

Clinical pharmacokinetics of drugs used in the treatment of gastrointestinal diseases (Part I).

Drug treatment of gastrointestinal diseases, which was previously limited to the use of antacids, anticholinergics, antispasmodics, cathartics and laxatives, has changed markedly over the past decade. Histamine H2-receptor antagonists (e.g. cimetidine, ranitidine and more recently famotidine and nizatidine) have revolutionised the treatment of peptic acid disorders, but their role is currently challenged by muscarinic-M1-receptor antagonists (e.g. pirenzepine), proton pump inhibitors (e.g. omeprazole), prostaglandin analogues and site-protective drugs (e.g. colloidal bismuth subcitrate and sucralfate). Newer antiemetics with prokinetic properties (e.g. metoclopramide, domperidone and cisapride) have also been introduced in the management of gastrointestinal motility disturbances, and new anti-inflammatory salicylates (e.g. olsalazine and mesalazine) have been developed for the treatment of chronic inflammatory bowel diseases. Finally, diphenoxylate and loperamide have gained wide clinical application as nonspecific antidiarrhoeal agents. The basic pharmacokinetic properties of the above agents are briefly reviewed with the main emphasis on the newer and more important drugs in current use. Furthermore, the effects of age and disease on pharmacokinetics, in addition to drug interaction potentials and pharmacokinetic-pharmacodynamic relationships, are discussed. The anti-inflammatory salicylates, nonspecific antidiarrhoeal agents, laxatives and cathartics will be dealt with in Part II.

Review: clinical trials in peptic ulcer disease--problems of methodology and interpretation.

This review focuses on the methodology and interpretation of drug trials in peptic ulcer disease. The problems of planning and conduct that are discussed include the ethics of using placebo, eligibility criteria, estimations of sample size, stopping rules, randomization, blinding, and efficacy criteria, that is, ulcer healing and pain relief in the short term and prevention of relapse and complications in the long term. Statistical topics covered include confidence intervals, evaluation of survival type data, post-stratification, and sub-group analysis. The difference between clinical and statistical significance is discussed, major problems being overemphasis on P-value, type II errors, and post hoc power determinations. Explanatory and pragmatic questions are based on compliance-to-protocol and intention-to-treat cohorts, respectively, and involve problems of compliance testing, evaluation of withdrawals, and the use of fixed-dose regimens. The rather slow process for clinical trials to gain acceptance is described, and it is proposed to rely on disease-related and behavioural barriers, lack of knowledge of the inherent limitations of methodology, and overemphasis on the subject of peptic ulcer healing, in addition to some concern at the relevance of assessing long-term drug intervention by repeated endoscopies rather than by studying symptoms and the incidence of complications. We foresee an increased impact of clinical trials on ulcer research and therapeutic decision making, provided physicians are able to develop the proper methodology to answer the relevant questions.

Is it possible to predict treatment response to a proton pump inhibitor in functional dyspepsia?

BACKGROUND: The efficacy of proton pump inhibitors in functional dyspepsia is modest and the prognostic factors are almost unknown. METHODS: Data were pooled on patients (n = 826) with a diagnosis of functional dyspepsia from two placebo-controlled trials who were treated with omeprazole, 10 or 20 mg once daily, for 4 weeks. Self-administered questionnaires for the assessment of symptoms and health-related quality of life were completed before entry, and epigastric pain/discomfort was recorded on diary cards. Treatment success was defined as the complete absence of epigastric pain/discomfort on each of the last 3 days of week 4. Prognostic factors were identified by multiple logistic regression analysis. RESULTS: The most discriminating predictor of treatment success (P < 0.0001) was the number of days with epigastric pain/discomfort during the first week of treatment. Fewer days with symptoms during the first week led to higher response rates at 4 weeks. In addition, age > 40 years, bothersome heartburn, low scores for bloating, epigastric pain and diarrhoea, history of symptoms for < 3 months and low impairment of vitality at baseline were identified as positive predictors of outcome. CONCLUSIONS: Early response to treatment with a proton pump inhibitor, during the first week, seems to predict the outcome after 4 weeks in patients with functional dyspepsia.

Esomeprazole 20 mg maintains symptom control in endoscopy-negative gastro-oesophageal reflux disease: a controlled trial of 'on-demand' therapy for 6 months.

BACKGROUND: Most patients with gastro-oesophageal reflux disease (GERD), regardless of endoscopic status, suffer symptomatic relapse within 6 months of stopping acid suppressant therapy. AIM: To assess the efficacy of 'on-demand' treatment of GERD with esomeprazole, the first proton pump inhibitor developed as an optical isomer. METHODS: In this multicentre, double-blind study, 342 endoscopy-negative GERD patients demonstrating complete resolution of heartburn during the final week of a 4-week treatment period with esomeprazole 20 mg or omeprazole 20 mg once daily were randomized to receive esomeprazole 20 mg or placebo on demand (maximum of one dose per day) for a further 6 months. Use of rescue antacids was permitted. RESULTS: All 342 patients (191 males), aged 19-79 (mean 49) years, were evaluable in the intention-to-treat analysis. The proportion of patients who discontinued treatment due to insufficient control of heartburn was significantly higher among placebo compared to esomeprazole recipients (51% vs. 14%; P < 0.0001). Patients randomized to esomeprazole on-demand therapy remained in the study longer than those in the placebo group (mean 165 vs. 119 days). Over 50% took the study medication for periods of 1--3 consecutive days (esomeprazole) or 4--13 consecutive days (placebo). Use of antacids was > 2-fold higher among placebo recipients. The frequency of adverse events was similar in the two groups, when adjusted for time spent in the study, as were the clinical laboratory profiles. CONCLUSIONS: On-demand therapy with esomeprazole 20 mg is effective and well tolerated in maintaining symptom control in endoscopy-negative GERD.

Effect of 10 mg and 20 mg omeprazole daily on duodenal ulcer: double-blind comparative trial.

One-hundred and seventy-one patients with endoscopically proven duodenal ulcers were allocated at random to double-blind treatment with 10 or 20 mg of omeprazole in the morning for up to 4 weeks. Patients completed the study if ulcer healing and pain relief had occurred at 2 weeks. A total of 155 patients completed the trial. Patients treated with 20 mg of omeprazole daily responded significantly more rapidly than those treated with 10 mg of omeprazole daily (P less than 0.001; Cochran-Mantel-Haenszel test covering both time points), cumulative healing rates at 2 and 4 weeks were 74% (58/78) and 91% (71/78), respectively. The corresponding rates in the group treated with 10 mg daily were 48% (39/81) and 75% (58/77). Pain relief was again more pronounced during treatment with the larger dose (P less than 0.05; stratified Wilcoxon test). No major clinical or biochemical side effects were noted. An omeprazole dose of 20 mg daily is preferable to a lower dose for the treatment of duodenal ulcer disease in the short term.

Low-dose cyclosporin for Crohn's disease: implications for clinical trials.

Cyclosporin is a potent immunosuppressant, which has gained recent interest as a possible treatment for Crohn's disease. Chronic nephrotoxicity, however, has recently been demonstrated as a result of early treatment with high initial cyclosporin doses. We report the effect of a 3-month treatment with low-dose cyclosporin (5-7.5 mg kg-1 day-1) in 11 chronically active, therapy-resistant Crohn's disease patients. Eight of the 11 patients (72%) improved according to a clinical grading score and the Dutch Activity Index whereas 9/11 (82%) improved according to the Crohn's Disease Activity Index (P less than 0.05) after 1 month. Three patients were withdrawn despite clinical improvement. One developed arterial hypertension, one dropped out and one required surgical treatment due to a small bowel stricture. Five patients (45%) completed the treatment period with improved clinical scores. After tapering-off, two patients (18%) were better at follow-up. No serious side-effects were encountered and it is concluded that low-dose cyclosporin treatment should be further investigated in Crohn's disease.

Dose finding study of mosapride in functional dyspepsia: a placebo-controlled, randomized study.

BACKGROUND: Prokinetic agents have shown variable efficacy in the treatment of functional dyspepsia. Mosapride is a new prokinetic 5-hydroxytryptamine-4 agonistic agent. AIM: To evaluate the efficacy of three dosage regimens of mosapride compared with placebo in the treatment of functional dyspepsia. METHODS: Patients were randomly allocated to treatment with placebo or mosapride (5 mg b.d., 10 mg b.d. or 7.5 mg t.d.s.) in a double-blind, prospective, multicentre, multinational study. The change in symptom severity score from an untreated baseline week to the sixth week of treatment was used to compare treatment efficacy. RESULTS: There were 141, 140, 143 and 142 patients valid for evaluation in the intention-to-treat population in the placebo, mosapride 5 mg b.d., mosapride 10 mg b.d. and mosapride 7.5 mg t.d.s. groups, respectively. The mean changes in the overall dyspeptic symptom score were - 0.90, - 0.94, - 0.88 and - 0.89, respectively, and the proportions of patients feeling better at the end of the treatment period were 60%, 59%, 59% and 61%, respectively. No statistically significant difference was seen. CONCLUSIONS: Treatment of functional dyspepsia with mosapride was not superior to placebo. The result raises the question of whether treatment with prokinetic agents is appropriate for functional dyspepsia.

The role of acid suppression in patients with endoscopy-negative reflux disease: the effect of treatment with esomeprazole or omeprazole.

BACKGROUND: Patients with endoscopy-negative reflux disease have reflux symptoms, mainly heartburn, but not mucosal breaks characteristic of erosive oesophagitis. Standard-dose proton pump inhibitors can provide symptom relief in endoscopy-negative reflux disease but the effect of greater acid suppression has not been studied. AIM: To test the hypothesis that esomeprazole produces heartburn resolution in a greater proportion of patients with ENRD than omeprazole. METHODS: Three multi-centre randomized, controlled, double-blind, 4-week acute treatment studies were conducted in endoscopy-negative reflux disease patients. In study A (n = 1282), patients received either esomeprazole 40 mg, esomeprazole 20 mg or omeprazole 20 mg daily; in studies B (n = 693) and C (n = 670) patients received either esomeprazole 40 mg or omeprazole 20 mg (B), and esomeprazole 20 mg or omeprazole 20 mg (C), respectively. RESULTS: Resolution of heartburn at 4 weeks (no heartburn symptoms during the last 7 days) was achieved in similar proportions of patients in each treatment arm in study A (esomeprazole 40 mg, 56.7%; esomeprazole 20 mg, 60.5%; omeprazole 20 mg, 58.1%), study B (esomeprazole 40 mg, 70.3%; omeprazole 20 mg, 67.9%) and study C (esomeprazole 20 mg, 61.9%; omeprazole 20 mg, 59.6%). There were no significant differences between treatment groups within each study. CONCLUSIONS: More than 60% of endoscopy-negative reflux disease patients reported heartburn resolution but, after 4 weeks of therapy, these proportions did not differ significantly between treatments.

On demand therapy with omeprazole for the long-term management of patients with heartburn without oesophagitis--a placebo-controlled randomized trial.

AIM: To observe the natural course of gastro-oesophageal reflux disease (GERD) in patients without oesophagitis following effective symptom relief, and to determine the place of acid pump inhibitor therapy in the long-term management of these patients. METHODS: We investigated the efficacy of on-demand therapy with omeprazole 20 mg or 10 mg, or placebo in a double-blind, randomized multicentre trial. It involved 424 patients with troublesome heartburn without endoscopic evidence of oesophagitis in whom heartburn had been resolved with short-term treatment. Patients were told to take study medication on demand once daily on recurrence of symptoms until symptoms resolved over a 6-month period. They also had access to antacids. The primary efficacy variable was time to discontinuation of treatment, due to unwillingness to continue. RESULTS: According to life-table analysis, after 6 months the remission rates were 83% (95% CI: 77-89%) with omeprazole 20 mg, 69% (61-77%) with omeprazole 10 mg, and 56% (46-64%) with placebo (P < 0.01 for all intergroup differences). The mean (s.d.) number of study medications used per day in these groups was 0.43 (0.27), 0.41 (0.27) and 0.47 (0.27), respectively. The use of antacids was highest in the placebo group and lowest in the omeprazole 20 mg group. Treatment failure was associated with more than a doubling of antacid use, and a deterioration in patient quality of life. CONCLUSIONS: Approximately 50% of patients with heartburn who do not have oesophagitis need acid inhibitory therapy in addition to antacid medication to maintain a normal quality of life. On-demand therapy with omeprazole 20 mg, is an effective treatment strategy in these patients.

One-week triple therapy with esomeprazole provides effective eradication of Helicobacter pylori in duodenal ulcer disease.

BACKGROUND: Esomeprazole is the first proton pump inhibitor to be developed as an optical isomer for the treatment of acid-related diseases. METHODS: Four hundred and forty eight duodenal ulcer patients with Helicobacter pylori infection, confirmed by 13C-urea breath test (UBT), and no current ulcer, were randomised to double-blind treatment with esomeprazole 20 mg twice daily (b.d.) (n=224) or omeprazole 20 mg b.d. (n=224), in combination with amoxicillin 1 g b.d. and clarithromycin 500 mg b.d. for 1 week (EAC and OAC, respectively). A negative UBT at both 4 and 8 weeks after completing therapy indicated successful H. pylori eradication. RESULTS: Intention-to-treat (ITT) analysis comprised 400 patients (EAC, n=204; OAC, n=196) and per protocol (PP) analysis 377 patients (EAC, n=192; OAC, n=185). Eradication rates (95% confidence intervals) for ITT and PP populations were: EAC, 90% (85-94%) and 91% (86-94%); OAC, 88% (82-92%) and 91% (86-95%). Between-group differences in eradication rates were not statistically significant. Both regimens were well tolerated, with an adverse event profile and frequency typical of proton pump inhibitor plus antibiotic combination therapy. CONCLUSIONS: Esomeprazole-based triple therapy for 1 week is highly effective in eradicating H. pylori infection in duodenal ulcer disease, offers comparable efficacy to omeprazole-based therapy, and is well tolerated.