Oral Omeprazole in Bleeding Peptic Ulcer

Study Overview
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Brief Summary
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Find out if there is a significant difference between clinical outcome among the patients with bleeding peptic ulcer treated with oral omeprazole compared to those treated with intravenous omeprazole.

Detailed Description
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Globally, Peptic ulcer disease is the most common cause of upper gastrointestinal bleeding (UGIB), accounting for about 50% of cases. It remains a serious medical problem with significant morbidity and mortality (1, 2). However, in Egypt, bleeding peptic ulcer comes second to the bleeding varices in order of frequency (approximately 30%) (3). Over the past 20 years, mortality resulting from bleeding peptic ulcer significantly decreased through researches on primary endoscopic hemostasis, due to improvement in pre- and post-endoscopic management, as well as identification of patients at a risk of catastrophic events-for close observation and focused intensive management (4).However, the risk of patients with bleeding peptic ulcers significantly increased owing to the aging population with multiple comorbidities, as well as the increasing use of aspirin and non-steroidal anti-inflammatory drugs (5). Endoscopic therapy significantly reduces further bleeding, surgery, and mortality in patients with bleeding peptic ulcer and is now recommended as the first hemostatic modality for these patients. However, there is a high risk of peptic ulcer re-bleeding in 14-36% of patients, in spite of efficient endoscopic intervention (6). Intravenous proton pump inhibitors (PPIs) are effective as adjuvant pharmacotherapy in preventing re-bleeding in these patients (7). Gastric acid inhibits clot formation and promotes clot lyses and accordingly, disturbs hemostasis of ulcers in the stomach and duodenum (8). Therefore, reduction of gastric acid secretion can prevent ulcer re-bleeding. The use of high-dose intravenous PPIs is standard practice in the management of upper gastrointestinal bleeding (9). High dose IV PPI has faster adequate acid suppression effect (gastric acid PH > 6) than high dose oral PPI . In addition, Compared to standard dose of oral PPI, high dose oral PPI has faster acid suppression (10, 11). However, the optimal route, dose, and duration of PPI therapy after endoscopic therapy of a bleeding peptic ulcer remain controversial. UGIB continues to represent a signiﬁcant clinical and economic burden to society. Intravenous PPI therapy is more expensive than oral one. Therefore, the therapy has to be assessed from a cost-effectiveness perspective (12). Several controlled trials and meta-analyses have shown the comparable efficacy of IV and oral PPI in treating ulcers at high risk of re-bleeding after endoscopic therapy. However, further studies to confirm their results were recommended (13, 14). The investigators will evaluate and compare the efficacy and safety profile of oral PPI compared to IV PPI in preventing re-bleeding from peptic ulcers.

Official Title
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Oral Versus Intravenous Omeprazole in Management of Bleeding Peptic Ulcer: Randomized Controlled Trial

Conditions
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Bleeding Peptic Ulcer

Intervention / Treatment
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* Drug: Omeprazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Peptic ulcer of the esophagus (lower part), stomach, and duodenum with one or more endoscopic signs of high risk for re-bleeding (ulcer bed exhibiting active bleeding (spurting/oozing), non-bleeding visible vessel, and adherent clot). Exclusion Criteria: Pregnant patients. Pediatric patients (less than 18 years). Ulcer with endoscopic signs suspicious of neoplastic disease (greater than 3 cm, irregular shape, uneven base, irregular edges, moth eaten appearance of peri ulcer folds, associated with a mass) Use of PPI 14 days or less before enrollment. Other sources of UGIB. Bleeding tendency (platelet count <50,000/mL, prothrombin time > 14 sec, prothrombin concentration <30%, anticoagulant therapy) Uremia.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: comparison between oral and intravenous omeprazole in management of bleeding peptic ulcer
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: oral omeprazole<br>oral omeprazole in bleeding peptic ulcer after endoscopic therapy 40 mg twice daily for 72 hours | Drug: Omeprazole<br>* Pre endoscopically: all patients will receive 80 mg omeprazole by 30 minute IV infusion. After performing upper endoscopy (with initial hemostasis), the patient will be randomly allocated into two groups; group A patients will receive oral omeprazole, while group B patients are intended to receive IV omeprazole. For patients of group A, omeprazole 40 mg will be administrated orally every 12 hours for 72 hours. Regarding group B, continuous infusion of omeprazole will be administrated at a rate of 8 mg/hour, for 72 hours.<br>|
| Active Comparator: intravenous omeprazole<br>intravenous omeprazole in bleeding peptic ulcer after endoscopic therapy as continuous infusion at rate of 8 mg/hour for 72 hours | Drug: Omeprazole<br>* Pre endoscopically: all patients will receive 80 mg omeprazole by 30 minute IV infusion. After performing upper endoscopy (with initial hemostasis), the patient will be randomly allocated into two groups; group A patients will receive oral omeprazole, while group B patients are intended to receive IV omeprazole. For patients of group A, omeprazole 40 mg will be administrated orally every 12 hours for 72 hours. Regarding group B, continuous infusion of omeprazole will be administrated at a rate of 8 mg/hour, for 72 hours.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| recurrent bleeding | Re-bleeding will be suspected if hematemesis or melena recur or of the patient develop one or more of the following: orthostatic hypotension, unstable vital signs (systolic blood pressure< 90 mmHg and pulse rate> 120/min), reduction of hemoglobin level> 2 gm/dL (despite blood transfusion), during 24 hour period. | 15 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| -Length of hospital stay. -Admission to ICU. - Blood transfusion (number of units of packes RBCs) -Angioembolization. -Surgery for uncontrolled recurrent bleeding. |  | 15 days |