Effect of high-dose oral rabeprazole on recurrent bleeding after endoscopic treatment of bleeding peptic ulcers.
ABSTRACT: Background. The aim of this study was to compare the effect of high-dose oral rabeprazole versus high-dose IV PPI on rebleeding after endoscopic treatment of bleeding peptic ulcers. Methods. This was a two-center, prospective, randomized, controlled trial. Patients with a high-risk bleeding peptic ulcer had endoscopic hemostasis and were randomly assigned to the high-dose oral rabeprazole group (20?mg twice daily for 72 hours) or the high-dose IV omeprazole group (80?mg as a bolus injection followed by continuous infusion at 8?mg/h for 72 hours). Results. The study was stopped because of slow enrollment (total n = 106). The rebleeding rates within 3 days were 3.7% (2 of 54 patients) given oral rabeprazole and 1.9% (1 of 52 patients) given IV omeprazole (P = 1.000). The rebleeding rates after 3 days were 1.9% and 0% (P = 1.000), respectively. The surgical intervention rates were 3.7% and 0% (P = 0.495), and the mortality rates were 1.9% and 0% (P = 1.000), respectively. Conclusions. The effect of high-dose oral rabeprazole did not differ significantly from that of high-dose IV omeprazole on rebleeding, surgical intervention, or mortality after endoscopic treatment of bleeding peptic ulcers, but this requires further evaluation.
Project description:OBJECTIVES:Our aims were to assess risks of early rebleeding after successful endoscopic hemostasis for Forrest oozing (FIB) peptic ulcer bleeding (PUBs) compared with other stigmata of recent hemorrhage (SRH). METHODS:These were post hoc multivariable analyses of a large, international, double-blind study (NCT00251979) of patients randomized to high-dose intravenous (IV) esomeprazole (PPI) or placebo for 72?h. Rebleeding rates of patients with PUB SRH treated with either PPI or placebo after successful endoscopic hemostasis were also compared. RESULTS:For patients treated with placebo for 72?h after successful endoscopic hemostasis, rebleed rates by SRH were spurting arterial bleeding (FIA) 22.5%, adherent clot (FIIB) 17.6%, non-bleeding visible vessel (FIIA) 11.3%, and oozing bleeding (FIB) 4.9%. Compared with FIB patients, FIA, FIIB, and FIIA had significantly greater risks of rebleeding with odds ratios (95% CI's) from 2.61 (1.05, 6.52) for FIIA to 6.66 (2.19, 20.26) for FIA. After hemostasis, PUB rebleeding rates for FIB patients at 72?h were similar with esomeprazole (5.4%) and placebo (4.9%), whereas rebleed rates for all other major SRH (FIA, FIIA, FIIB) were lower for PPI than placebo, but the treatment by SRH interaction test was not statistically significant. CONCLUSIONS:After successful endoscopic hemostasis, FIB patients had very low PUB rebleeding rates irrespective of PPI or placebo treatment. This implies that after successful endoscopic hemostasis the prognostic classification of FIB ulcers as a high-risk SRH and the recommendation to treat these with high-dose IV PPI's should be re-evaluated.
Project description:BACKGROUND:The Forrest classification is widely applied to guide endoscopic hemostasis for peptic ulcer bleeding. Accordingly, practice guidelines suggest medical treatment only for ulcer with a Forrest IIc lesion because it has low rebleeding risk even without endoscopic therapy, ranging from 0 to 13%. However, the risk ranges widely and it is unclear who is at risk of rebleeding with such a lesion. This study assessed whether the Rockall score, which evaluates patients holistically, could indicate the risk of recurrent bleeding among patients with a Forrest IIc lesion at the second-look endoscopy. METHODS:Patients who had peptic ulcer bleeding with Ia-IIb lesions received endoscopic hemostasis at the primary endoscopy, and they were enrolled if their Ia-IIb lesions had been fading to IIc at the second-look endoscopy after 48- to 72-h intravenous proton pump inhibitor (PPI) infusion. Primary outcomes were rebleeding during the 4th-14th day and 4th-28th day after the first bleeding episode. RESULTS:The prospective cohort study enrolled 140 patients, who were divided into a Rockall scores???6 group or a Rockall scores?<?6 group. The rebleeding rates in the Rockall scores???6 group and the Rockall scores?<?6 group during the 4th-14th day and the 4th-28th day were 13/70 (18.6%) versus 2/70 (2.9%), p?=?0.003 and 17/70 (24.3%) versus 3/70 (4.3%), p?=?0.001, respectively, based on an intention-to-treat analysis and 5/62 (8.1%) versus 0/68 (0%), p?=?0.023 and 6/59 (10.2%) versus 0/67 (0%), p?=?0.009, respectively, based on a per-protocol analysis. The Kaplan-Meier curves showed that the Rockall scores???6 group had a significantly lower cumulative rebleeding-free proportion than the Rockall scores?<?6 group (p?=?0.01). CONCLUSIONS:Combined Rockall scores???6 on arrival with a Forrest IIc lesion at the second-look endoscopy can identify patients at risk of recurrent peptic ulcer bleeding following initial endoscopic and intravenous PPI treatment. Trial registration Trial registration identifier: NCT01591083.
Project description:BACKGROUND AND STUDY AIMS:The need for routine second-look endoscopy in cases of peptic ulcer bleeding remains uncertain. We investigated risk factors related to the need for second-look endoscopy after endoscopic hemostasis and proton pump inhibitor (PPI) infusion. PATIENTS AND METHODS:We prospectively enrolled 316 patients with peptic ulcer bleeding after endoscopic hemostasis. Second-look endoscopy was scheduled after 72-hour PPI infusion (Day-3 subgroup) or one day early (Day-2 subgroup). If early rebleeding developed within 3 days, emergent second-look endoscopy was conducted. Risk factors for early rebleeding (use of E2(nd) score to predict the need for early second-look endoscopy) and persistent major stigmata in the Day-3 subgroup (use of R2(nd) score to predict the need for routine second-look endoscopy) were analyzed using univariable and multivariable regression. RESULTS:Excluding 10 of 316 patients with early rebleeding, the rate of persistent major stigmata was lower in the Day-3 subgroup than in the Day-2 subgroup (4.8?% vs. 15.4?%, P??=?0.002). Endoscopic epinephrine-injection monotherapy and hypoalbuminemia?<?3.0?g/dL were two independent risk factors for early rebleeding (P????0.05). The Forrest Ia-Ib type and hypoalbuminemia?<?3.5?g/dL were two independent risk factors for persistent major stigmata on the day-3 second-look endoscopy (P??<?0.05). The E2(nd) score was highly accurate for prediction of early rebleeding (AUROC 0.86; 95?% CI, 0.73~0.99), and the R2(nd) score could predict persistent major stigmata at second-look endoscopy (AUROC 0.84; 95?% CI, 0.69~0.99). CONCLUSIONS:For patients with peptic ulcer bleeding, E2(nd) and R2(nd) scores can indicate the need for early and routine second-look endoscopy, respectively (Trial registration identifier: NCT02197039).
Project description:Upper gastrointestinal (GI) haemorrhage is a common cause for admission to hospital and is associated with a mortality of around 10%. Prompt assessment and resuscitation are vital, as are risk stratification of the severity of bleeding, early involvement of the multidisciplinary team and timely access to endoscopy, preferably within 24 h. The majority of bleeds are due to peptic ulcers for which Helicobacter pylori and non-steroidal anti-inflammatory agents are the main risk factors. Although proton pump inhibitors (PPIs) are widely used before endoscopy, this is controversial. Pre-endoscopic risk stratification with the Glasgow Blatchford score is recommended as is the use of the Rockall score postendoscopy. Endoscopic therapy, with at least two haemostatic modalities, remains the mainstay of treating high-risk lesions and reduces rebleeding rates and mortality. High-dose PPI therapy after endoscopic haemostasis also reduces rebleeding rates and mortality. Variceal oesophageal haemorrhage is associated with a higher rebleeding rate and risk of death. Antibiotics and vasopressin analogues are advised in suspected variceal bleeding; however, endoscopic variceal band ligation remains the haemostatic treatment of choice. Balloon tamponade remains useful in the presence of torrential variceal haemorrhage or when endoscopy fails to secure haemostasis, and can be a bridge to further endoscopic attempts or placement of a transjugular intrahepatic portosystemic shunt. This review aims to provide an update on the latest evidence-based recommendations for the management of acute upper GI haemorrhage.
Project description:A 24-week, double-blind, clinical trial of rabeprazole for the prevention of recurrent peptic ulcers caused by low-dose aspirin (LDA) has been reported, but trials for longer than 24 weeks have not been reported. The aim of this study is to assess the long-term efficacy and safety of rabeprazole for preventing peptic ulcer recurrence on LDA therapy. Eligible patients had a history of peptic ulcers on long-term LDA (81 or 100 mg/day) therapy. Patients with no recurrence of peptic ulcers at the end of the 24-week double-blind phase with rabeprazole (10- or 5-mg once daily) or teprenone (50 mg three times daily) entered the extension phase. Rabeprazole doses were maintained for a maximum of 76 weeks, including the double-blind 24-week period and the extension phase period (long-term rabeprazole 10- and 5-mg groups). Teprenone was randomly switched to rabeprazole 10 or 5 mg for a maximum of 52 weeks in the extension phase (newly-initiated rabeprazole 10- and 5-mg groups). The full analysis set consisted of 151 and 150 subjects in the long-term rabeprazole 10- and 5-mg groups, respectively, and the cumulative recurrence rates of peptic ulcers were 2.2 and 3.7%, respectively. Recurrent peptic ulcers were not observed in the newly-initiated rabeprazole 10- and 5-mg groups. No bleeding ulcers were reported. No clinically significant safety findings, including cardiovascular events, emerged. The use of long-term rabeprazole 10- and 5-mg once daily prevents the recurrence of peptic ulcers in subjects on low-dose aspirin therapy, and both were well-tolerated.
Project description:BACKGROUND: Peptic ulcers with active bleeding or a non-bleeding visible vessel require aggressive endoscopic treatment. AIMS: To determine whether endoscopic adrenaline injection alone or contact probe therapy following injection is a suitable treatment for peptic ulcer bleeding. METHODS: A total of 96 patients with active bleeding or non-bleeding visible vessels received adrenaline alone, bipolar electrocoagulation alone, or combined treatment (n=32 in each group). RESULTS: Initial haemostasis was not achieved in one patient in the adrenaline group, two in the gold probe group, and two in the injection gold probe group (p>0.1). Rebleeding episodes were fewer in the injection gold probe group (2/30, 6.7%) than in the gold probe group (9/30, 30%, p=0.04) and in the adrenaline group (11/31, 35.5%, p=0.01). Treatment failure (other therapy required) was rarer in the injection gold probe group (4/32, 12.5%) than in the adrenaline group (12/32, 37.5%, p=0.04). The volume of blood transfused after entry of the study was less in the injection gold probe group (mean 491 ml) than in the adrenaline group (1548 ml, p<0. 0001) and the gold probe group (1105 ml, p<0.01). Duration of hospital stay, numbers of patients requiring urgent surgery, and death rate were not statistically different among the three groups. CONCLUSIONS: For patients with peptic ulcer bleeding, combined adrenaline injection and gold probe treatment offers an advantage in preventing rebleeding and decreasing the need for blood transfusion.
Project description:Obesity is associated with a risk of gastroesophageal reflux disease. The pharmacodynamic efficacy of proton pump inhibitors has not been specifically evaluated in obese subjects. The aim of this study was to compare the antisecretory response to a single oral dose of 20 mg rabeprazole, 20 mg omeprazole and placebo in obese subjects.Gastric pH was monitored for 24 hours on three separate occasions in eighteen H. pylori-negative, asymptomatic obese subjects. Subjects were given omeprazole, rabeprazole or placebo in a randomized order and in a double-blind fashion. The main analysis criterion was 24-h percent of time post dose with intragastric pH above 3; secondary criteria were percentage of time above pH 4, median pH, [H+] concentrations and nocturnal acid breakthrough (NAB). Results were analyzed using linear mixed models and Wilks test comparing variances.24-h median [IQ] percentages of time with gastric pH above 3 and 4 were higher with rabeprazole than omeprazole (46 [37-55] vs. 30 [15-55] %, 9 [5-11] % for placebo) but the differences did not reach statistical significance (p = 0.11 and 0.24, respectively). Median acid concentrations were significantly lower with rabeprazole than with omeprazole and placebo (22 [14-53] vs. 54 [19-130] and 95 [73-170] mmoles/l, p < 0.01) for all periods. The number of NAB was significantly lower with rabeprazole than with omeprazole (median 1 [1,2] vs. 2 [1-3], p = 0.04). Variances of 24-h data (pH above 3 and 4, median pH, [H+] concentrations) were significantly lower with rabeprazole than with omeprazole (p < 0.0001).In asymptomatic obese subjects the gastric antisecretory response to a single dose of rabeprazole and omeprazole was strong and not significantly different between drugs despite a significantly more homogeneous response with rabeprazole.ClinicalTrial.gov: NCT01136317.
Project description:A second endoscopic method together with injection therapy is recommended to treat high-risk bleeding peptic ulcers. This study investigated whether additional argon plasma coagulation (APC) treatment could influence hemostatic efficacy following endoscopic injection therapy to treat high-risk bleeding ulcers.From October 2010 to January 2012, eligible patients with high-risk bleeding ulcers were admitted to our hospital. They prospectively randomly underwent either APC therapy along with distilled water injection or distilled water injection alone. Episodes of rebleeding were retreated with endoscopic combination therapy. Patients in whom retreatment was ineffective underwent emergency surgery or transarterial embolization (TAE).A total of 116 enrolled patients were analyzed. The hemostatic efficacy in 58 patients treated with APC along with distilled water injection was compared with that in 58 patients treated with distilled water injection alone. The 2 treatment groups were similar with respect to all baseline characteristics. Initial hemostasis was accomplished in 56 patients treated with combined therapy, and 55 patients treated with distilled water injection therapy (97% vs 95%, P = 0.648). Bleeding recurred in 2 patients treated with combined therapy, and 9 patients treated with distilled water injection (3.6% vs 16%, P = 0.029). Treatment method was the only independent prognostic factor for recurrent bleeding (odds ratio 0.17; 95% confidence interval 0.03-0.84; P = 0.029). The 2 groups did not differ significantly in hospital stay, TAE, surgery, and mortality.Endoscopic therapy with APC following distilled water injection is more effective than distilled water injection alone for preventing rebleeding of peptic ulcer.
Project description: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.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.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).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.NCT01123031.
Project description:Adding a second endoscopic therapy to epinephrine injection might improve hemostatic efficacy in patients with high-risk bleeding ulcers but the optimum modality remains unknown. We aimed to estimate the comparative efficacy of different dual endoscopic therapies for the management of bleeding peptic ulcers through random-effects Bayesian network meta-analysis.Different databases were searched for controlled trials comparing dual therapy versus epinephrine monotherapy or epinephrine combined with another second modality until September, 30 2016. We estimated the ORs for rebleeding, surgery and mortality among different treatments. Adverse events were also evaluated.Seventeen eligible articles were included in the network meta-analysis. The addition of mechanical therapy (OR 0.19, 95% CrI 0.07-0.52 and OR 0.10, 95% CrI 0.01-0.50, respectively) after epinephrine injection significantly reduced the probability of rebleeding and surgery. Similarly, patients who received epinephrine plus thermal therapy showed a significantly decreased rebleeding rate (OR 0.30, 95% CrI 0.10-0.91), as well as a non-significant reduction in surgery (OR 0.47, 95% CrI 0.16-1.20). Although differing, epinephrine plus mechanical therapy did not provide a significant reduction in rebleeding (OR 0.62, 95% CrI 0.19-2.22) and surgery (OR 0.21, 95% CrI 0.03-1.73) compared to epinephrine plus thermal therapy. Sclerosant failed to confer further benefits and was ranked highest among the 5 treatments in relation to adverse events.Mechanical therapy was the most appropriate modality to add to epinephrine injection. Epinephrine plus thermal coagulation was effective for controlling high risk bleeding ulcers. There was no further benefit with sclerosants with regard to rebleeding or surgery, and sclerosants were also associated with more adverse events than any other modality.