BACKGROUND/AIMS: Proton pump inhibitors has high efficacy in alone or with endoscopic intervention for peptic ulcer bleeding (PUB). However, the dose and treatment duration of PPIs needed to prevent re-bleeding are not well established. Our aim is to compare highdose infusion of pantoprazole (standard treatment) and low-dose bolus pantoprazole in patients given endoscopic treatment for control of PUB. METHODS: This study was a singlecenter, prospective, randomized, double-blind, double-dummy, comparative pilot study. The Ethics Committee of Mersin University approved this study and all patients provided written informed consent. Patients admitted with PUB in which the bleeding was controlled by endoscopic intervention (sclerotherapy with epinephrine) were randomized to a highdose group (Pantoprazole 80 mg IV bolus followed by 8 mg/h IV infusion for 72 h) or a low dose group (Pantoprazole 80 mg IV bolus followed by 40 mg IV bolus every 12 h for 72 h). A double-dummy technique was used to keep the patients blinded, so all patients in the low-dose group received isotonic saline infusion for 3 days as placebo. After 3 days of treatment, all patients were given oral Pantoprazole (40 mg bid) until day-30. The primary endpoints were early re-bleeding (within 72 h), need for blood transfusion, surgery due to bleeding, mortality, and duration of hospitalization. Cost of treatment was also determined. RESULTS: Total 73 patients enrolled the study. There were 36 patients in the high-dose group and were 37 patients in the low-dose group. There were no significant differences between the two treatment groups in age, gender, reason for admission, presence of comorbid diseases, Hb level at admission, drug use, smoking, alcohol use, and Rockall score. Re-bleeding occurred in 10 patients (27.8%) in the high-dose group and in 3 patients (8.1%) in the low-dose group (p = 0.028). The mean blood transfusion dose was 4.5±4.2 units in the high dose group and 2.5±2.2 units in the low dose group (p = 0.040). Rate of surgery (2/ 1), and mortality (3/2), and duration of hospitalization (5.6±3.4 days/5.0±5.2 days) were similar in the two groups (p-values of 0.536, 0.710, and 0.575, respectively). The cost of pantoprazole per patient was 252.62 Turkish Liras (168.41 USD) in the high-dose group and 104.02 Turkish Liras (69.30 USD) in the low-dose group. There was no side effect related to any pantoprazol medications. CONCLUSIONS: Low-dose pantoprazole treatment after successful endoscopic therapy in PUB was as effective as high-dose. Also there was less rebleeding, and need for transfusion in low-dose group. The low-dose treatment had lower costs and was easier to administer. Thus, low-dose bolus pantoprazole administration following successful endoscopic therapy should be considered for treatment of PUB
BACKGROUND: After therapeutic endoscopy is performed in high-risk patients with peptic ulcer bleeding, rebleeding occurs in about 25 to 30%. High dose intravenous proton pump inhibitors (PPI) have been recommended for the use in high-risk patients to prevent rebleeding following successful therapeutic endoscopy.
OBJECTIVE: Compare the efficacy between pantoprazole high dose bolus injections and continuous intravenous infusion to prevent rebleeding in peptic ulcer patients after initial hemostasis is achieved by the therapeutic endoscopy.
MATERIAL AND METHOD: A clinical block randomized control trial was conducted at Maharaj Nakorn Chiang Mai Hospital in massive peptic ulcer bleeding patients. All patients underwent endoscopic diagnosis and treatment within six hours of admission. Hemostasis was achieved by therapeutic endoscopy in 28 patients who received 80 mg pantoprazole as a loading dose before intervention. They were randomized into two groups. The first group was given a high dose of pantoprazole, 40 mg bolus injections twice daily for seven days (n = 13). The second group was given continuous intravenous infusion of pantoprazole, 8 mg per hour for the first three days, followed with a 40 mg bolus injection twice daily similar to the first group from day 4 until day 7 (n = 15). After the seventh day, both groups were given 20 mg of oral pantoprazole once daily for two months. The data was analyzed by Fisher's exact test to compare the frequency of rebleeding within seven days after therapeutic endoscopy.
RESULTS: The frequency of recurrent bleeding between the high dose pantoprazole bolus injection group and the continuous intravenous infusion group was not significantly different, 30.8% and 33.3% respectively (p = 1.0). Three patients in the high dose bolus group and five in the continuous infusion group underwent surgery (p = 0.68). There was no statistically significant difference between the two groups by volume of blood transfusion, length of hospital stay, or mortality.
CONCLUSION: In the present study, both PPI drug administration methods showed an equally effective for massive peptic ulcer bleeding. Further studies with a larger sample size are recommended.
BACKGROUND AND AIMS: Proton pump inhibitors (PPIs) are generally used to prevent delayed bleeding after endoscopic submucosal dissection (ESD) and to heal the artificial ulcers. However, it remains controversial whether PPIs or histamine-2 receptor antagonists (H(2) RAs) are more effective in preventing delayed bleeding after ESD. We prospectively compared the effects of omeprazole and famotidine in preventing delayed bleeding and promoting artificial ulcer healing after ESD.
METHODS: A total of 158 patients (155 early gastric cancers and three adenomas) were randomly assigned to the PPI group (omeprazole 20 mg/day) or H(2) RA group (famotidine 40 mg/day) in a prospective randomized controlled trial. The primary end point was the incidence of hematemesis, melena, and/or a decrease in hemoglobin level of 2 g/dL or more requiring endoscopic hemostatic treatment. ESD-induced ulcer healing and changes in ulcer size were also compared at 6 weeks after ESD as a secondary end point.
RESULTS: Of the 158 patients, two were excluded from analysis because they had been treated with a PPI before the present study. Accordingly, data from 77 PPI and 79 H(2) RA subjects were included for analysis. Delayed bleeding after ESD occurred in 6.5% of subjects (PPI group) and in 6.3% (H(2) RA group); there was no significant difference between the two groups. Likewise, the two groups were not significantly different with respect to ulcer stage or ulcer size reduction rate.
CONCLUSIONS: Proton pump inhibitors are not superior to H(2) RAs for the prevention of delayed bleeding or the healing of artificially induced ulcers after ESD.
BACKGROUND: High 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.
METHODS: Patients 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.
RESULTS: From 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).
CONCLUSION: Patients 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 REGISTRATION: NCT01123031.
BACKGROUND: The optimal dosage of intravenous proton pump inhibitors (PPIs) for the prevention of peptic ulcer rebleeding remains unclear.
AIM: To compare the rebleeding rate of high-dose and standard-dose PPI use after endoscopic haemostasis.
METHODS: A total of 201 patients with bleeding ulcers undergoing endoscopic treatment with epinephrine injection and heater probe thermocoagulation were randomised to receive a high-dose regimen (80 mg bolus, followed by pantoprazole 8 mg/h infusion, n = 100) or a standard-dose regimen (pantoprazole 40 mg bolus daily, n = 101). After 72 h, all patients were given 40 mg pantoprazole daily orally for 27 days.
RESULTS: There were no statistical differences in mean units of blood transfused, length of hospitalisation ≦5 days, surgical or radiological interventions and mortality within 30 days between two groups. Bleeding recurred within 30 days in six patients [6.2%, 95% confidence interval (CI) 1.3-11.1%] in the high-dose group, as compared to five patients (5.2%, 95% CI 0.6-9.7%) in the standard-dose group (P = 0.77). The stepwise Cox regression analysis showed end-stage renal disease, haematemesis, chronic obstructive pulmonary disease (hazard ratio: 37.15, 10.07, 9.12, 95% CI: 6.76-204.14, 2.07-49.01, 1.66-50.00 respectively) were independent risk factors for rebleeding and Helicobacter pylori infection was associated with lower risk of rebleeding (hazard ratio: 0.20, 95% CI: 0.04-0.94).
CONCLUSIONS: Following combined endoscopic haemostasis of bleeding ulcers, co-morbidities, haematemesis and H. pylori Status, but not PPI dosage, are associated with rebleeding (http://www.Clinical Trials.gov.ID: NCT00709046).
OBJECTIVES: The use of intravenous proton-pump inhibitors (PPIs) has shown to reduce recurrent bleeding and improve patient outcome after endoscopic hemostasis on patients with peptic ulcer. However, the efficacy of oral PPI is uncertain. Studies from Asia indicated that even oral PPI can achieve the same therapeutic effect. This study is designed to compare the efficacy of high-dose intravenous PPI to oral PPI in preventing recurrent bleeding after endoscopic hemostasis.
METHODS: This is a single-center, randomized-controlled, double-blind, and double-dummy study. Patients had Forrest IA/IB or IIA/IIB peptic ulcer bleeding and received endoscopic hemostasis before recruitment into the study. They were randomized to receive either (i) esomeprazole IV bolus at a dose of 80 mg plus infusion at 8 mg/h for 72 h and oral placebo every 12 h (IVP group), or (ii) IV placebo bolus plus infusion for 72 h and high-dose oral esomeprazole at a dose of 40 mg every 12 h (ORP group). Patients were followed up for 30 days after index bleeding. The primary end point was defined as the 30-day recurrent bleeding after successful endoscopic hemostasis.
RESULTS: A total of 118 patients were randomized to the IVP group and 126 to the ORP group in this study. In all, 39.8% in the IVP and 42.9% in the ORP group used non-steroidal anti-inflammatory drug and/or aspirin before bleeding. In the IVP group (vs. ORP), Forrest IA represented 1.7% (5.6%), IB 41.5% (38.1%), IIA 52.5% (50.8%), and IIB 4.2% (5.6%). Recurrent bleeding in 30 days was reported in 7.7% of patients in the IVP group and 6.4% of patients in the ORP group, and the difference of recurrent bleeding was −1.3% (95% CI: −7.7%, 5.1%). There was no difference in blood transfusion, repeated endoscopic therapy, and hospital stay between the two groups.
CONCLUSIONS: High-dose oral esomeprazole at 40 mg BID may be considered as a useful alternative to IV bolus plus infusion of esomeprazole in the management of ulcer bleeding in patients who are not candidates for high-dose IV infusion. However, as this study was stopped prematurely and was not designed as an equivalency trial, a much larger study would be necessary to document whether there is equivalency or non-inferiority of the two treatments in a heterogeneous patient population.
BACKGROUND: Proton pump inhibitors have been reported to be more useful than histamine-2 receptor antagonists for the prevention of bleeding after endoscopic submucosal dissection (ESD) for superficial gastric neoplasia. The aim of this study was to assess the effects of the proton pump inhibitor lansoprazole and the histamine-2 receptor antagonist roxatidine for the prevention of bleeding and the promotion of ulcer healing after ESD and to compare the cost-effectiveness of these two drugs.
METHODS: The study subjects were 129 patients who underwent ESD for superficial gastric neoplasia. The patients were randomly assigned to the lansoprazole group (L group) or the roxatidine group (R group). Either drug was administered intravenously from the morning of the ESD day to the day after the ESD, followed by oral treatment for an additional 8 weeks. A second-look endoscopy was performed on the day after the ESD, and a repeat endoscopy was performed at 8 weeks after the ESD. The incidence of bleeding and the ulcer-healing rate at 8 weeks after the ESD were analyzed, as well as the total cost of treatment with these antisecretory agents.
RESULTS: Three patients in each group were excluded from the analysis, leaving 62 patients in L group and 61 in R group. Two of the 62 patients (3.2%) in L group and three of the 61 patients (4.9%) in R group showed bleeding after ESD ; there was no significant difference between the two groups (P = 0.68). The ulcer-healing rate was 93.5% (58/62) in L group and 93.4% (57/61) in R group (P = 1). The total cost of treatment with the antisecretory agent from the day of the ESD to day 56 after the ESD was Yen 13,212 for lansoprazole and Yen 5,841 for roxatidine.
CONCLUSIONS: Roxatidine appears to have high cost-effectiveness in the prevention of bleeding and in the promotion of ulcer healing after ESD for superficial gastric neoplasia.
BACKGROUND: Proton pump inhibitors (PPIs) decrease the rate of rebleeding following endoscopic hemostatic therapy in patients with bleeding peptic ulcers. This study compares the efficacy of oral omeprazole vs intravenous pantoprazole in decrease of rebleeding of peptic ulcer patients.
METHODS: One hundred and six patients with high risk peptic ulcer were randomized to receive either oral omeprazole (80 mg BID for 3 days) or IV pantoprazole (80 mg bolus and 8 mg/hour infusion for 3 days) followed by omeprazole (20 mg each day for 30 days). All patients underwent upper endoscopy and endoscopic therapy within 24 hours.
RESULTS: Seventeen patients were excluded from the study. Forty four patients were randomly allocated into omeprazole group and 41 patients to IV pantoprazole group. Both groups were similar for factors affecting the outcome. Bleeding reoccurred in five patients of omeprazole group and four patients in pantoprazole group (11.4% vs 9.8 %). The mean hospital stay and blood transfusion were not different in both groups.
CONCLUSION: Oral omeprazole and IV pantoprazole had equal effects on prevention of rebleeding after endoscopic therapy in patients with high risk bleeding peptic ulcers.
Proton pump inhibitors has high efficacy in alone or with endoscopic intervention for peptic ulcer bleeding (PUB). However, the dose and treatment duration of PPIs needed to prevent re-bleeding are not well established. Our aim is to compare highdose infusion of pantoprazole (standard treatment) and low-dose bolus pantoprazole in patients given endoscopic treatment for control of PUB.
METHODS:
This study was a singlecenter, prospective, randomized, double-blind, double-dummy, comparative pilot study. The Ethics Committee of Mersin University approved this study and all patients provided written informed consent. Patients admitted with PUB in which the bleeding was controlled by endoscopic intervention (sclerotherapy with epinephrine) were randomized to a highdose group (Pantoprazole 80 mg IV bolus followed by 8 mg/h IV infusion for 72 h) or a low dose group (Pantoprazole 80 mg IV bolus followed by 40 mg IV bolus every 12 h for 72 h). A double-dummy technique was used to keep the patients blinded, so all patients in the low-dose group received isotonic saline infusion for 3 days as placebo. After 3 days of treatment, all patients were given oral Pantoprazole (40 mg bid) until day-30. The primary endpoints were early re-bleeding (within 72 h), need for blood transfusion, surgery due to bleeding, mortality, and duration of hospitalization. Cost of treatment was also determined.
RESULTS:
Total 73 patients enrolled the study. There were 36 patients in the high-dose group and were 37 patients in the low-dose group. There were no significant differences between the two treatment groups in age, gender, reason for admission, presence of comorbid diseases, Hb level at admission, drug use, smoking, alcohol use, and Rockall score. Re-bleeding occurred in 10 patients (27.8%) in the high-dose group and in 3 patients (8.1%) in the low-dose group (p = 0.028). The mean blood transfusion dose was 4.5±4.2 units in the high dose group and 2.5±2.2 units in the low dose group (p = 0.040). Rate of surgery (2/ 1), and mortality (3/2), and duration of hospitalization (5.6±3.4 days/5.0±5.2 days) were similar in the two groups (p-values of 0.536, 0.710, and 0.575, respectively). The cost of pantoprazole per patient was 252.62 Turkish Liras (168.41 USD) in the high-dose group and 104.02 Turkish Liras (69.30 USD) in the low-dose group. There was no side effect related to any pantoprazol medications.
CONCLUSIONS:
Low-dose pantoprazole treatment after successful endoscopic therapy in PUB was as effective as high-dose. Also there was less rebleeding, and need for transfusion in low-dose group. The low-dose treatment had lower costs and was easier to administer. Thus, low-dose bolus pantoprazole administration following successful endoscopic therapy should be considered for treatment of PUB
