Intravenous Esomeprazole Research Articles

Double oral esomeprazole after a 3-day intravenous esomeprazole infusion reduces recurrent peptic ulcer bleeding in high-risk patients: a randomised controlled study

BackgroundPatients with high Rockall scores have increased risk of ulcer rebleeding after 3-day esomeprazole infusions.ObjectiveTo investigate whether double oral esomeprazole given after a 3-day esomeprazole infusion decreases ulcer rebleeding for...

Pharmacokinetics, pharmacodynamics, and safety of esomeprazole injection/infusion in healthy Chinese volunteers: A five-way crossover study

Esomeprazole provides effective and long lasting inhibition of gastric acid secretion. However, the pharmacokinetics and pharmacodynamics of intravenous esomeprazole in the Chinese population remain unclear. To compare the pharmacokinetics and pharmacodynamics of intravenous esomeprazole (injection and infusion) and their clinical safety and tolerability in healthy Chinese subjects. A randomized, single-center, open-label, five-way crossover study was conducted in 20 healthy volunteers. CYP2C19 metabolizer genotype and Helicobacter pylori status were examined. Five dosing regimens were used: single 40 mg injection, 40 mg infusion every 12 h, 40 mg infusion followed by continuous infusion at 8 mg/h, 80 mg infusion followed by continuous infusion at 4 or 8 mg/h. Intragastric pH was recorded within 24 h. Plasma concentration-time curve, maximum plasma concentration (Cmax ), steady state concentration, and total plasma clearance were determined. Adverse events were also recorded. Continuous infusion resulted in a higher mean area under the curve and Cmax than injection. There were no significant differences among the four infusion groups in terms of percentages of time at pH > 4, > 5, > 6, > 7 within 24 h and pH > 6 within the first 3 h. There were no significant differences in pharmacokinetic or pH values among variants of CYP2C19 genotype. The pH value within 24 h was unaffected by H. pylori infection in subjects with continuous infusion. Esomeprazole administrated by infusion produces better pharmacokinetic and intragastric pH profiles compared with those by injection. The optimal administration schedule for esomeprazole in Chinese subjects is infusion with 40 mg/12 h.

Isotretinoin-Induced Esophagitis in an Immunocompetent Patient

Purpose: A 31-year-old woman with acne presented with severe, progressive odynophagia over 10 days. She initially had intolerance to solid foods, then liquids. Due to an inability to tolerate anything by mouth, including saliva, she was admitted. She denied ever having GERD and the only medications she was taking included oral contraception, a multivitamin, and isotretinoin. She started the isotretinoin 3 weeks prior to admission and was adamant that she took her pills with copious water. Physical examination and labs were unremarkable. CMV PCR, HIV serologies were negative. She was treated with high-dose intravenous esomeprazole, calcium carbonate, magic mouthwash, and viscous lidocaine with minimal relief. An EGD demonstrated LA Grade D esophagitis with bleeding and superficial ulcerations from 25 cm from the incisors to the GE junction at 40cm. The patient was started empirically on intravenous acyclovir without improvement. Subsequent HSV-1 and HSV-2 IgM titers were elevated, and IgG titers were normal. Afterwards, biopsies showed active esophagitis with ulcer, PAS-D stain negative for fungi, and negative immunostains for HSV-1, HSV-2, and CMV. Over the week, the patient gradually improvement from viscous lidocaine and was eventually discharged with plans to hold isotretinoin indefinitely. The etiology of the esophagitis was initially thought to be from HSV. HSV esophagitis can affect immunocompetent patients and manifest as odynophagia, heartburn, and fever. The serologies were suggestive of an acute infection, but the lack of response to acyclovir and negative viral cytopathology and immunohistochemistry makes HSV less likely. Other causes such as CMV and fungi were also ruled out. Severe GERD was unlikely due to the lack of typical symptoms. Given the temporal relation to the initiation of isotretinoin, this was considered the most likely etiology. Isotretinoin-induced esophagitis has only been reported once. In that case, the patient presented with dysphagia and rapidly improved after cessation of isotretinoin and the addition of daily omeprazole and antacids. The authors of that case hypothesized that the esophageal injury was due to both mechanical and biochemical causes, not allergic, due to the patient's subsequent tolerance of the medication on a rechallenge with instructions to drink copious water with pill ingestion. Isotretinoin may cause mucosal injury via its effects on innate and adaptive immunity. Recently, isotretinoin has been associated with increased risk of ulcerative colitis. Patients taking isotretinoin should be instructed to drink copious water, and if they experience odynophagia or dysphagia, isotretinoin-induced esophagitis should be considered.

Phase I, Multicenter, Randomized, Open-Label Study Evaluating the Pharmacokinetics and Safety Profile of Repeated Once-Daily Doses of Intravenous Esomeprazole in Children 0 to 17 Years of Age

BackgroundSeveral oral proton pump inhibitors (PPIs) are currently approved for use in pediatric patients in North America and Europe. However, when use of oral therapy is not possible or appropriate, intravenous formulations of PPIs may be helpful. Intravenous esomeprazole is approved in the United States for the short-term treatment of gastroesophageal reflux disease (GERD) with erosive esophagitis in adults and in pediatric patients 1 month to 17 years of age (inclusive) as an alternative to oral therapy. Four open-label, randomized, 2-way crossover studies in adults with GERD found no clinically relevant differences in acid suppression between repeated doses of oral and intravenous esomeprazole. However, the pharmacokinetics of intravenous esomeprazole has not been studied extensively in children. ObjectiveThe aim of this study was to evaluate steady-state pharmacokinetics and tolerability of repeated doses of intravenous esomeprazole in children. MethodsIn this multicenter, open-label study, hospitalized patients (0–17 years of age) considered for acid suppression therapy received once-daily intravenous esomeprazole sodium for injection at 0.5 mg/kg (0–1 month of age), 1.0 mg/kg (1–11 months of age), 10 mg (1–5 years of age), 10 or 20 mg (6–11 years of age), or 20 or 40 mg (12–17 years of age) for 4 days. Children 6 to 11 years of age (inclusive) were randomized in a 1:1 ratio to receive esomeprazole 10 or 20 mg, and adolescents 12 to 17 years of age (inclusive) were randomized in a 1:1 ratio to receive esomeprazole 20 or 40 mg. Blood samples were drawn pre- and post-dose. Plasma esomeprazole was measured using reversed-phase liquid chromatography and mass spectrometry. Pharmacokinetic variables were derived using mixed-effects modeling. Adverse events (AEs) were assessed. ResultsFifty-nine patients were randomized and 57 received the study drug. A majority of patients were white (44 white, 5 black/African American, 3 Asian, 5 other) and male (35/57). Fifty patients were eligible for pharmacokinetic analysis, including 6 to 8 patients in each age group. Esomeprazole pharmacokinetics was dose proportional and related to weight and age. Clearance increased with increasing weight and age. The mean AUCτ ranged from 6.9 μmol · h/L (10 mg, 6–11 years) to 17.6 μmol · h/L (40 mg, 12–17 years). The mean Css,max ranged from 3.7 μmol/L (0.5 mg/kg, 0–1 month) to 10.5 μmol/L (40 mg, 12–17 years). Thirty-one patients experienced 1 or more AEs; 6 patients experienced 1 or more treatment-unrelated serious AEs. ConclusionsIntravenous esomeprazole at doses resulting in targeted AUCτ and Css,max similar to therapeutic exposure in adults appeared to be reasonably well tolerated in this small, select pediatric population. ClinicalTrials.gov identifier: NCT00474019.

Oral versus intravenous proton pump inhibitors in preventing re-bleeding for patients with peptic ulcer bleeding after successful endoscopic therapy

BackgroundHigh dose intravenous proton pump inhibitor after endoscopic therapy for peptic ulcer bleeding has been recommended as adjuvant therapy. Whether oral proton pump inhibitor can replace intravenous proton pump inhibitor in this setting is unknown. This study aims to compare the clinical efficacy of oral and intravenous proton pump inhibitor after endoscopic therapy.MethodsPatients with high-risk bleeding peptic ulcers after successful endoscopic therapy were randomly assigned as oral lansoprazole or intravenous esomeprazole group. Primary outcome of the study was re-bleeding rate within 14 days. Secondary outcome included hospital stay, volume of blood transfusion, surgical intervention and mortality within 1 month.ResultsFrom April 2010 to Feb 2011, 100 patients were enrolled in this study. The re-bleeding rates were 4% (2/50) in the intravenous group and 4% (2/50) in the oral group. There was no difference between the two groups with regards to the hospital stay, volume of blood transfusion, surgery or mortality rate. The mean duration of hospital stay was 1.8 days in the oral lansoprazole group and 3.9 days in the intravenous esomeprazole group (p > 0.01).ConclusionPatients receiving oral proton pump inhibitor have a shorter hospital stay. There is no evidence of a difference in clinical outcomes between oral and intravenous PPI treatment. However, the study was not powered to prove equivalence or non-inferiority. Future studies are still needed.Trial registrationNCT01123031

1079 Effects of Intravenous and Oral Esomeprazole in Prevention of Recurrent Bleeding From Peptic Ulcers After Endoscopic Therapy

1079 Effects of Intravenous and Oral Esomeprazole in Prevention of Recurrent Bleeding From Peptic Ulcers After Endoscopic Therapy

Effect of Intravenous Esomeprazole 40 mg and Pantoprazole 40 mg on Intragastric pH in Healthy Subjects

<i>Objective</i>: The aim of this study was to compare the effect on intragastric acidity over 24 h on days 1 and 3 following treatment with intravenous (i.v.) esomepra-zole 40 mg (CAS for esomeprazole sodium: 161796-78-7) and pantoprazole 40 mg (CAS for pantoprazole sodium: 138786-67-1). <i>Methods</i>: In an open, randomised, two-way cross-over study, 36 healthy volunteers received esomeprazole (Nexium^®) 40 mg or pantoprazole 40 mg, both administered once daily as an i.v. bolus injection for 3 consecutive days. Continuous 24-h pH recordings were made under standardised conditions at baseline and on days 1 and 3 of each treatment period. The primary variable was the percentage of time with intragastric pH > 4 during a 24-h period. <i>Results</i>: Time with intragastric pH > 4 was significantly greater with esomeprazole than with pantoprazole during the first 4 h (47.8 % vs. 18.9 %), as well as for the 24-h period of day 1 and day 3 (day 1: 38.8 % vs. 23.7 %; day 3: 55.0 % vs. 35.2 %, p<0.0001 for all times examined). Mean of median intragastric pH with esome-prazole was significantly higher than with pantoprazole during the 24-h period (day 1: 3.2 vs. 2.2, p<0.0001; day 3: 4.3 vs. 3.1, p<0.00001). <i>Conclusion</i>: Esomeprazole administered as a 40 mg i.v. bolus injection provided faster and more effective control of intra-gastric acidity than a 40 mg i.v. bolus injection of pantoprazole, and also maintained pH > 4 longer both during the first 4 h on day 1 and during the 24-h period of day 1 and day 3 of dosing.

Elevated Amylase and Lipase Mimicking Pancreatitis: Diagnostic Pitfall

Purpose: Introduction: Serum amylase and lipase levels are standard tests to diagnose acute pancreatitis. However, they can be elevated in various clinical settings, including acute gastroenteritis or chronic alcoholism. Recognition is particularly important because using an elevated amylase or lipase level to diagnose acute pancreatitis may not be appropriate. We herein present a case of elevated amylase and lipase levels in the absence of acute pancreatitis. Case Presentation: A 56-year-old male with chronic alcoholism presented with nausea and vomiting for 5 days. He denied abdominal pain, fever or diarrhea. His past medical history was insignificant. He admitted alcohol abuse, notably hard liquors, which constituted his major dietary intake. His vital signs were T 96.9F, HR 90 /min, BP 142/91 mmHg, SpO2 97% on room air. He appeared disheveled. His heart sounds were regular and lungs were clear to auscultation. His abdomen was soft, bowel sounds were diminished but no tenderness was present. His complete blood count and metabolic panel were normal. His liver panel showed a slightly elevated ALT level of 90 U/L with normal bilirubin, ALP and ALT level. Serum amylase and lipase level was found to be 216 mg/dL and 702 mg/dL respectively. His alcohol level was 404 mg/dL. Ultrasonography showed fatty infiltration in the liver with intact pancreas, spleen and gallbladder. Subsequent esophagogastroduodenoscopy (EGD) revealed nonerosive gastritis. He was treated with intravenous fluids and esomeprazole. The following day, amylase and lipase level went down to 123 mg/dL and 437 mg/dL respectively. Discussion: Serum amylase or lipase levels are recognized as a useful marker for pancreatic inflammation. However, there are several other conditions that can cause hyperamylasemia or hyperlipasemia, such as gut perforation and renal failure. In this case, elevated amylase and lipase was probably due to acute gastritis and chronic alcoholism, considering the totally benign abdominal examination as well as the EGD findings. Although gastroenteritis in not widely considered as a cause of hyperamylasemia or hyperlipasemia, numerous cases have reported with possible specific pathogenesis. It may result from pancreatic involvement in the inflammatory process or from increased absorption of pancreatic enzymes from the intestinal lumen. Also, according to the literature, elevated serum lipase levels have been found in 11 to 33% of asymptomatic alcoholics. Therefore, acute gastroenteritis and chronic alcoholism should be included in the differential diagnosis of hyperamylasemia or hyperlipasemia. Extra caution should be exercised when interpreting elevated amylase and lipase mimicking pancreatitis.

Intravenous Esomeprazole

Intravenous esomeprazole (Nexium®) is approved in Europe for the prevention of rebleeding following therapeutic endoscopy for acute bleeding gastric or duodenal ulcers. In a pivotal clinical trial, patients with peptic ulcer bleeding and high-risk stigmata who received intravenous esomeprazole for 72 hours following endoscopic haemostatic therapy were significantly less likely than those receiving intravenous placebo to experience recurrent peptic ulcer bleeding at days 3, 7 and 30. In addition, the need for repeat endoscopic haemostatic therapy, the total amount of blood transfused and the number of additional hospital days required because of rebleeding were significantly lower in intravenous esomeprazole recipients than in intravenous placebo recipients. All patients received oral esomeprazole for 27 days following intravenous study drug administration. Intravenous esomeprazole was generally well tolerated in the pivotal trial, with infusion-site reactions being among the most commonly reported adverse events. Two pharmacoeconomic analyses conducted from a healthcare payer perspective used decision-tree models with 30-day time horizons to examine the cost effectiveness and cost utility of intravenous esomeprazole in patients with bleeding peptic ulcers who had undergone endoscopic haemostatic therapy. With regard to the incremental cost per bleed averted, intravenous esomeprazole was predicted to be dominant in Spain and cost effective in Sweden and the US compared with no intravenous esomeprazole. Efficacy results and resource utilization data from the pivotal clinical trial were inputted into this model, and the results of the analysis were generally robust to plausible variations in key variables. In the cost-utility analysis, which was conducted in the UK and is available as an abstract and poster, esomeprazole was considered to be the most cost-effective treatment alternative, compared with omeprazole or pantoprazole. For this analysis, clinical outcomes data were obtained from a systematic review and mixed treatment comparison (given the absence of head-to-head trial data), and utility values were proxied from the literature. In conclusion, intravenous esomeprazole prevents peptic ulcer rebleeding in patients who have undergone endoscopic haemostatic therapy. Pharmacoeconomic analyses support the use of intravenous esomeprazole following endoscopic haemostatic therapy in patients with peptic ulcer bleeding and high-risk stigmata.

Safety and tolerability of high-dose intravenous esomeprazole for prevention of peptic ulcer rebleeding

Efficacy of a continuous high-dose intravenous infusion of esomeprazole, followed by an oral regimen after successful endoscopic therapy for peptic ulcer bleeding (PUB) was established in the PUB study (ClinicalTrials. gov identifier: NCT00251979). Mortality rates and detailed safety and tolerability results from this study are reported here. This was a double-blind, randomized study in patients ≥18 years with overt signs of upper gastrointestinal bleeding, following endoscopic diagnosis of a single gastric or duodenal ulcer (≥5 mm) with stigmata indicating current/ recent bleeding (Forrest class Ia, Ib, IIa, or IIb). Postendoscopic hemostasis, patients received intravenous esomeprazole (80 mg/30 minutes, then 8 mg/hour for 71.5 hours) or placebo. Postinfusion, all patients received open-label oral esomeprazole 40 mg once daily for 27 days. Mortality rates were analyzed using Fisher's exact test; other safety variables were analyzed descriptively. A total of 767 patients were randomized; 764 comprised the safety analysis set (375 patients received esomeprazole, 389 placebo). Baseline characteristics were similar across the two treatment groups. Three deaths from the esomeprazole treatment group and eight from the placebo group occurred during the trial (0.8% versus 2.1%; P=0.22). From these 11 all-cause deaths, one (esomeprazole group; rebleeding from duodenal ulcer) occurred during the 72-hour intravenous treatment phase. Adverse event (AE) frequency was similar for the two groups over the intravenous treatment phase (esomeprazole, 39.2%; placebo, 41.9%), with gastrointestinal disorders being most commonly reported (12.3% and 19.8%, respectively). Serious AEs were mostly related to bleeding events. Infusion-site reactions (mild, transient) were reported in 4.3% of esomeprazole-treated patients versus 0.5% of placebo patients. These did not lead to treatment discontinuation. Esomeprazole, given as a continuous high-dose intravenous infusion followed by an oral regimen after successful endoscopic therapy for PUB, was well tolerated, with no apparent safety concerns from either the high-dose intravenous treatment or oral phases.

Cost reduction associated with restriction policy on dispensing intravenous esomeprazole in lebanon

To assess the impact of the pharmacist on cost through simple implementation of restriction policy on IV drug usage during pharmacy dispensing procedure. In-patient floors of a Hospital. All medication orders for IV esomeprazole, received at the pharmacy during a 24-month period, were reviewed for appropriate IV route of administration. Two separate time intervals, pre- and post- implementation of restriction dispensing policy, were used to determine cost impact of pharmacy intervention. The cost difference between pre- and post-restriction periods. During the pre-restriction period, the majority of esomeprazole IV vials were dispensed to patients able to tolerate oral medications and who were admitted to non-intensive care units. The average monthly consumption of IV esomeprazole was 1,439 vials in the pre-restriction period as compared to 346 vials in the post-restriction period. Therefore, the associated cost was reduced by an average of $21,233 per month. Even though the clinical role of pharmacy practice in Middle Eastern countries is limited, this study highlighted the impact of the pharmacist on cost through the implementation of restriction policy during dispensing procedure, leading to a cost reduction by four folds.

Cost–effectiveness of high-dose intravenous esomeprazole in patients with peptic ulcer bleeding in the USA and Europe

Evaluation of: Barkun AN, Adam V, Sung JJ et al. Cost effectiveness of high-dose intravenous esomeprazole for peptic ulcer bleeding. Pharmacoeconomics 28(3), 217–230 (2010).Peptic ulcer bleeding (PUB) is life-threatening and associated with high healthcare costs. Clinical outcomes in PUB depend largely on the risk of rebleeding. Recent data indicate that intravenous proton pump inhibitors (PPIs) reduce rebleeds, the need for surgery and repeat endoscopic treatment. From a policy perspective, it is important to assess the cost–effectiveness of this treatment. Accordingly, a decision-tree model published by Barkun et al. evaluated the costs and benefits of high-dose intravenous esomeprazole in preventing rebleeds in patients with PUB based on data from a multinational, randomized clinical trial comparing this therapeutic approach to intravenous placebo. The results indicate that esomeprazole is cost effective in the USA and Sweden, and cost saving in Spain. These findings agree with most other analyses of intravenous PPIs used in PUB patients at high risk for bleeds. The therapeutic approach provides increased benefits to patients at a relatively small additional cost.

Intravenous esomeprazole pharmacodynamics in critically ill patients

Objective:A widely held belief contends that food-induced proton pump activation is important for optimal proton pump inhibitor–induced inhibition of gastric acid secretion. This study was undertaken to assess intragastric acid control with intravenous (IV) esomeprazole in critically ill patients.Research design and methods:This open-label, single-arm, exploratory trial was conducted at five university or regional hospital intensive care units in the US. Adult patients admitted to an intensive care unit who required mechanical ventilation and had at least one additional risk factor for stress-induced ulcer received twice-daily IV esomeprazole 40 mg for 48 hours and could continue for another 24 hours if no prepyloric enteral feedings were planned.Clinical trial registration:Trial registration: ClinicalTrials.gov identifier: NCT00428701.Main outcome measures:The primary efficacy variable was the linear-interpolated percentage of time intragastric pH was ≥4 during 24–48 hours. Secondary efficacy variables included the interpolated percentage of time intragastric pH was ≥4 during 0–24, 0–48, and 48–72 hours, the percentage of gastric aspirates collected with pH ≥4 during 0–24, 24–48, 0–48, and 48–72 hours, and time to stable pH ≥4. Safety was assessed based on adverse events (AEs), physical examinations, vital signs, laboratory tests, and electrocardiograms.Results:Forty-five patients were enrolled (one was excluded because of previous partial gastrectomy). Interpolated mean percentage time pH ≥4 was 88.8%, 80.7%, and 83.5% for 24–48, 0–24, and 0–48 hours, respectively. For 0–72 hours, ≥78% of gastric aspirates had pH ≥4. Median time to stable pH was 1 hour (95% confidence interval: 0.67, 2.00). Treatment was well tolerated, with no evidence of gastrointestinal bleeding. A total of 75 AEs occurred in 34 patients, none considered treatment related.Conclusions:In this noncontrolled exploratory study, twice-daily IV esomeprazole 40 mg rapidly decreased intragastric acidity and effectively maintained pH ≥4 during 0–72 hours in fasting, critically ill, mechanically ventilated patients at high risk for stress ulcers.

Cost Effectiveness of High-Dose Intravenous Esomeprazole for Peptic Ulcer Bleeding

Peptic ulcer bleeding (PUB) is a serious and sometimes fatal condition. The outcome of PUB strongly depends on the risk of rebleeding. A recent multinational placebo-controlled clinical trial (ClinicalTrials.gov identifier: NCT00251979) showed that high-dose intravenous (IV) esomeprazole, when administered after successful endoscopic haemostasis in patients with PUB, is effective in preventing rebleeding. From a policy perspective it is important to assess the cost efficacy of this benefit so as to enable clinicians and payers to make an informed decision regarding the management of PUB. Using a decision-tree model, we compared the cost efficacy of high-dose IV esomeprazole versus an approach of no-IV proton pump inhibitor for prevention of rebleeding in patients with PUB. The model adopted a 30-day time horizon and the perspective of third-party payers in the USA and Europe. The main efficacy variable was the number of averted rebleedings. Healthcare resource utilization costs (physician fees, hospitalizations, surgeries, pharmacotherapies) relevant for the management of PUB were also determined. Data for unit costs (prices) were primarily taken from official governmental sources, and data for other model assumptions were retrieved from the original clinical trial and the literature. After successful endoscopic haemostasis, patients received either high-dose IV esomeprazole (80 mg infusion over 30 min, then 8 mg/hour for 71.5 hours) or no-IV esomeprazole treatment, with both groups receiving oral esomeprazole 40 mg once daily from days 4 to 30. Rebleed rates at 30 days were 7.7% and 13.6%, respectively, for the high-dose IV esomeprazole and no-IV esomeprazole treatment groups (equating to a number needed to treat of 17 in order to prevent one additional patient from rebleeding). In the US setting, the average cost per patient for the high-dose IV esomeprazole strategy was $US14 290 compared with $US14 239 for the no-IV esomeprazole strategy (year 2007 values). For the European setting, Sweden and Spain were used as examples. In the Swedish setting the corresponding respective figures were Swedish kronor (SEK)67 862 ($US9220 at average 2006 interbank exchange rates) and SEK67 807 ($US9212) [year 2006 values]. Incremental cost-effectiveness ratios were $US866 and SEK938 ($US127), respectively, per averted rebleed when using IV esomeprazole. For the Spanish setting, the high-dose IV esomeprazole strategy was dominant (more effective and less costly than the no-IV esomeprazole strategy) [year 2008 values]. All results appeared robust to univariate/threshold sensitivity analysis, with high-dose IV esomeprazole becoming dominant with small variations in assumptions in the US and Swedish settings, while remaining a dominant approach in the Spanish scenario across a broad range of values. Sensitivity variables with prespecified ranges included lengths of stay and per diem assumptions, rebleeding rates and, in some cases, professional fees. In patients with PUB, high-dose IV esomeprazole after successful endoscopic haemostasis appears to improve outcomes at a modest increase in costs relative to a no-IV esomeprazole strategy from the US and Swedish third-party payer perspective. Whereas, in the Spanish setting, the high-dose IV esomeprazole strategy appeared dominant, being more effective and less costly.

A single dose of intravenous esomeprazole decreases gastric secretion in healthy volunteers

Data suggest that esomeprazole decreases gastric secretion. To assess the effect of a single i.v. esomeprazole dose on gastric secretion volume 3 h after drug administration, as a primary endpoint, and to evaluate, as secondary endpoints, the reduction 1 and 5 h after dosing; time when the gastric pH was <2.5 and esomeprazole's safety. In all, 23 healthy Helicobacter pylori-negative volunteers (10 men, 13 women, mean age 28.2 +/- 6) participated in this single-centre, randomized, double-blind, placebo-controlled, 2-way, single-dose cross-over study. In different sessions, volunteers received i.v. either esomeprazole 40 mg or placebo. An inserted double-lumen nasogastric tube perfused and aspirated gastric liquid. Mechanical fractioned aspiration measured secretion volume; aliquot spectrophotometry assessed gastric secretion volume lost to the duodenum. Three hours post-i.v. esomeprazole, average gastric secretion decreased by 77.6% (vs. baseline) compared to placebo. Values 1 and 5 h after dosing were 73.5% and 74.5%. Five hours after esomeprazole, the gastric pH was <2.5 3.9% of the time and 73.3% after placebo (P < 0.002). Esomeprazole was well-tolerated. No serious adverse events occurred. Intravenous esomeprazole decreases gastric secretions. The potential clinical impact in averting bronchoaspiration during anaesthesia induction and in intensive care patients should be investigated in further studies.

Intravenous esomeprazole for prevention of recurrent peptic ulcer bleeding

Intravenous esomeprazole for prevention of recurrent peptic ulcer bleeding

225 Intravenous Esomeprazole for Prevention of Peptic Ulcer Re-Bleeding in a Predominantly Caucasian Population: Results On Clinical Benefits and Hospital Resource Use

and quantified CagA translocation by Western blot using anti-phosphotyrosine and antiCagA antibodies. Significantly higher levels of CagA were translocated by the 7.13 0310mutant compared to wild-type H. pylori strain 7.13. By utilizing proteomics technology to contrast two closely related H. pylori strains that induce distinct phenotypes, we have shown that HP0310 may function to alter levels of peptidoglycan, thereby affecting the composition of substrates translocated by the cag secretion system. These studies also provide an important foundation for investigating the role of bacterial virulence factors in H. pylori-induced pathologic sequelae, as such results would ultimately allow for generation of a profile of H. pylori proteins to use for screening persons infected with strains most likely to induce severe disease.

Is There a Subgroup of Patients with Forrest IB (Oozing) Peptic Ulcer Bleeding At Increased Risk of Re-Bleeding?

Background: A dichotomy exists among peptic ulcer bleeds (PUB) of oozing appearance (Forrest class Ib), in that a clot or visible vessel is apparent in some cases. Whether such stigmata increase the risk of re-bleeding remains unknown. As part of a recent study of acid-suppressive therapy after successful endoscopic therapy for PUB with high-risk stigmata [1], we report a re-assessment by the study Endpoint Committee (EpC) of re-bleeding among patients (pts) with Forrest Ib (oozing) ulcers to determine whether a subgroup indeed exists that exhibits increased risk of re-bleeding. Methods: In this double-blind, randomized clinical trial (NCT00251979), intravenous esomeprazole (80mg infusion over 30min, then 8mg/h for 71.5h) was compared with matching placebo for prevention of re-bleeding after successful endoscopic hemostasis of PUB. All patients had a single bleeding gastric or duodenal ulcer (≥5 mm diameter, treated endoscopically). Post-infusion, both groups received open-label oral esomeprazole 40mg qd for 27d. As part of the present analysis, the rate of clinically significant re-bleeding (large volume hematemesis, presence of 2 of 3 possible clinical signs of re-bleeding [recurrent melena, drop in Hct, unstable BP or pulse]) within 30d was evaluated for those with Forrest Ib ulcers before endoscopic hemostasis. Baseline ulcer photo documentation was independently re-evaluated by the EpC (DMJ and RS) and Forrest Ib ulcers were further subclassified according to the presence/absence of a clot or visible vessel. Results: A total of 273 pts with Forrest Ib ulcers and available photo documentation were evaluated and reclassified. There was agreement among the EpC on the presence of a clot or visible vessel, respectively, in 90 pts (33.0%). In such pts, the re-bleeding rate was 10.0% (9/90) vs 0% (0/29) in those where the EpC agreed on the absence of a clot or visible vessel (p=.09). In the remaining cases, where the EpC did not agree on the presence/absence of a clot or visible vessel, the re-bleeding rate was 6.5% (10/154). Hence, the re-bleeding rate in the Forrest Ib subgroup with a clot or visible vessel was similar to that of the overall study population (10.7%). Conclusions: Among PUB pts with Forrest Ib (oozing) ulcers, a subgroup with both a clot or a visible vessel and oozing appears to have an increased risk of re-bleeding vs those with only oozing and no additional stigmata. Modification of the Forrest Ib classification may therefore increase its precision in identifying PUB pts with a higher risk of re-bleeding.Supported by AstraZeneca R&D, Mölndal, Sweden[1] Sung JJY, et al. GUT 2008;57 Suppl. II: A70

Intravenous Esomeprazole for Prevention of Recurrent Peptic Ulcer Bleeding

Use of proton-pump inhibitors in the management of peptic ulcer bleeding is controversial because discrepant results have been reported in different ethnic groups. To determine whether intravenous esomeprazole prevents recurrent peptic ulcer bleeding better than placebo in a multiethnic patient sample. Randomized trial conducted between October 2005 and December 2007; patients, providers, and researchers were blinded to group assignment. 91 hospital emergency departments in 16 countries. Patients 18 years or older with peptic ulcer bleeding from a single gastric or duodenal ulcer showing high-risk stigmata. Intravenous esomeprazole bolus, 80 mg, followed by 8-mg/h infusion, over 72 hours or matching placebo, each given after successful endoscopic hemostasis. Intervention was allocated by computer-generated randomization. After infusion, both groups received oral esomeprazole, 40 mg/d, for 27 days. The primary end point was rate of clinically significant recurrent bleeding within 72 hours. Recurrent bleeding within 7 and 30 days, death, surgery, endoscopic re-treatment, blood transfusions, hospitalization, and safety were also assessed. Of 767 patients randomly assigned, 764 provided data for an intention-to-treat analysis (375 esomeprazole recipients and 389 placebo recipients). Fewer patients receiving intravenous esomeprazole (22 of 375) had recurrent bleeding within 72 hours than those receiving placebo (40 of 389) (5.9% vs. 10.3%; difference, 4.4 percentage points [95% CI, 0.6% to 8.3%]; P = 0.026). The difference in bleeding recurrence remained significant at 7 days and 30 days (P = 0.010). Esomeprazole also reduced endoscopic re-treatment (6.4% vs. 11.6%; difference, 5.2 percentage points [95% CI of difference, 1.1 percentage points to 9.2 percentage points]; P = 0.012), surgery (2.7% vs. 5.4%), and all-cause mortality rates (0.8% vs. 2.1%) more than placebo, although differences for the latter 2 comparisons were not significant. About 10% and 40% of patients in both groups reported serious and nonserious adverse events, respectively. Endoscopic therapy was not completely standardized; some patients received epinephrine injection, thermal coagulation, or hemoclips alone, whereas others received combination therapy, but there were similar proportions with single therapy in each group. High-dose intravenous esomeprazole given after successful endoscopic therapy to patients with high-risk peptic ulcer bleeding reduced recurrent bleeding at 72 hours and had sustained clinical benefits for up to 30 days. AstraZeneca Research and Development.

Intravenous Esomeprazole for Prevention of Recurrent Peptic Ulcer Bleeding: A Randomized Trial

Intravenous Esomeprazole for Prevention of Recurrent Peptic Ulcer Bleeding: A Randomized Trial