Peptic Ulcer Hemorrhage
Conditions
Keywords
peptic ulcer bleeding, rabeprazole, proton pump inhibitor
Brief summary
This study is conducted to compare and evaluate the effect of administering a high-dose intravenous proton pump inhibitors or high-dose oral Rabeprazole in preventing recurrent bleeding after the endoscopic treatment of bleeding peptic ulcers.
Detailed description
0.1 % of hospitalized patients are attributed to upper gastrointestinal bleeding every year in the U.S. and Europe, among which peptic ulcer is the most common cause of upper gastrointestinal bleeding. Endoscopic hemostasis procedure in the management of bleeding due to peptic ulcers was safe as well as effective and lowered recurrent bleeding, surgery and mortality. Endoscopic treatment is widely used as an effective and safe method but it has disadvantages including the need for the endoscopy specialist and the likelihood of developing the complications such as perforation or recurrent bleeding although they rarely occur. Thus, less invasive medical treatments with fewer side effects have been continuously studied and among them, gastric acid inhibitors have been studied the most.Acid and pepsin inhibit platelet aggregation, activation of blood coagulation system, and fibrinogen polymerization. Blood clots already formed are digested by pepsin and the activity of pepsin is closely related to intragastric pH level. Therefore, it is known that an elevated intragastric pH facilitates hemostasis process, induces hemostasis by stabilizing hematoma and prevents recurrent bleeding. To suffice these conditions, it is reported that a potent gastric acid inhibitor is needed to maintain intragastric pH of 6 or higher. For the treatment of bleeding peptic ulcers, the intravenous administration of a high-dose proton pump inhibitor after the initial endoscopic treatment has shown a decline in the frequency of recurrent bleeding as well as surgery. Recent studies reported that the use of oral proton pump inhibitor was effective under certain circumstances in the treatment of bleeding peptic ulcers. However, to date, no study has been conducted to compare the effect of a high-dose intravenous proton pump inhibitor with that of oral Rabeprazole after endoscopic treatment of bleeding peptic ulcers. Therefore, in this study, after administering a high-dose intravenous proton pump inhibitor or high-dose oral Rabeprazole in preventing recurrent bleeding following endoscopic treatment of bleeding peptic ulcers, we are going to compare the rate of recurrent bleeding between the two groups as well as to compare and evaluate the surgery rate, mortality rate and the number of days of hospital stay.
Interventions
DRUGomeprazole sodium IV
Intravenous Omeprazole (brand name: Losec® injection 40 mg) 80 mg as a bolus injection followed by continuous infusion at 8 mg per hour for 3 days. From Day 4, oral Rabeprazole 10 mg once daily for 6 weeks as maintenance therapy.
DRUGRabeprazole
Oral Rabeprazole 20 mg twice daily for 3 days. From Day 4, oral Rabeprazole 10 mg once daily for 6 weeks as maintenance therapy.
Sponsors
Janssen Korea, Ltd., Korea
The Catholic University of Korea
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Bleeding peptic ulcer: Among patients suspected to have upper GI bleeding based on hematemesis or melena, those with peptic ulcers(Forrest I, IIa and IIb) in whom active bleeding, non-bleeding visible vessels and fresh blood clots are observed on upper GI endoscopy performed within 24 hours after the hospitalization * patients who achieved primary hemostasis with endoscopic hemostasis procedure via upper GI endoscopy
Exclusion criteria
* Patients who refuse endoscopic procedure * Patients with complications from gastric ulcer that require operative treatment prior to upper GI endoscopic treatment(e.g., gastric outlet obstruction, peptic ulcer perforation) * Pregnancy * Patients with serious concurrent diseases such as malignant tumors or end-stage diseases * History of previous gastrectomy or vagotomy * Known hypersensitivity to proton pump inhibitors * Elderly patients * Epilepsy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Rebleeding Within 3 Days | day 3 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rebleeding After 3 Days | 6wk | Rebleeding after 3 days was assessed by checking the patients from day 3 to discharge and bleeding event or regular follow-up after discharge to week 6. |
| Surgery | 6wk | This sencodary endpoint surgery is the operation for bleeding control of peptic ulcer bleeding such as gastric or duodenal primary closure, and subtotal gastrectomy with/without vagotomy. |
| Death | 6wk | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Mean Units of Blood Transfusion | day 3 | In order to compare the total amount of blood transfusion, mean units of blood transfusion was used. |
| Duration of Hospital Stay | 6wk | — |
Countries
South Korea
Participant flow
Recruitment details
1. Location: Uijeongbu St. Mary's hospital and Bucheon St. Mary's hospital, The Catholic University of Korea 2. Period: from April 1, 2006 to April 19, 2007 and from October 1, 2007 to December 31, 2008.
Pre-assignment details
Patients who presented with overt or suspected upper gastrointestinal bleeding were eligible. These eligible patients were required to have an high-risk bleeding peptic ulcer on emergent endoscopy performed within 24 hours after the hospitalization. Among those, patients who achieved primary hemostasis with endoscopic hemostatic treatment.
Participants by arm
| Arm | Count |
|---|---|
| Rabeprazole Sodium Oral Rabeprazole 20 mg twice daily for 3 days. From Day 4, oral Rabeprazole 10 mg once daily for 6 weeks as maintenance therapy. | 54 |
| Omeprazole Intravenous Omeprazole 80 mg as a bolus injection followed by continuous infusion at 8 mg per hour for 3 days. From Day 4, oral Rabeprazole 10 mg once daily for 6 weeks as maintenance therapy. | 52 |
| Total | 106 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | detection of exclusion criteria | 4 | 3 |
| Overall Study | Lost to Follow-up | 21 | 14 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Rabeprazole Sodium | Omeprazole | Total |
|---|---|---|---|
| Age Continuous | 56.1 years STANDARD_DEVIATION 16.2 | 57.1 years STANDARD_DEVIATION 15.8 | 56.6 years STANDARD_DEVIATION 16 |
| Region of Enrollment Korea, Republic of | 54 participants | 52 participants | 106 participants |
| Sex: Female, Male Female | 8 Participants | 13 Participants | 21 Participants |
| Sex: Female, Male Male | 46 Participants | 39 Participants | 85 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 54 | 2 / 52 |
| serious Total, serious adverse events | 0 / 54 | 0 / 52 |
Outcome results
Primary
Rebleeding Within 3 Days
Time frame: day 3
Population: intention to treat (ITT)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rabeprazole Sodium | Rebleeding Within 3 Days | 2 participants |
| Omeprazole | Rebleeding Within 3 Days | 1 participants |
p-value: <0.05Fisher Exact
Secondary
Death
Time frame: 6wk
Population: intention to treat (ITT)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rabeprazole Sodium | Death | 1 participants |
| Omeprazole | Death | 0 participants |
p-value: <0.05Fisher Exact
Secondary
Rebleeding After 3 Days
Rebleeding after 3 days was assessed by checking the patients from day 3 to discharge and bleeding event or regular follow-up after discharge to week 6.
Time frame: 6wk
Population: intention to treat (ITT)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rabeprazole Sodium | Rebleeding After 3 Days | 1 participants |
| Omeprazole | Rebleeding After 3 Days | 0 participants |
p-value: <0.05Fisher Exact
Secondary
Surgery
This sencodary endpoint surgery is the operation for bleeding control of peptic ulcer bleeding such as gastric or duodenal primary closure, and subtotal gastrectomy with/without vagotomy.
Time frame: 6wk
Population: intention to treat (ITT)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rabeprazole Sodium | Surgery | 2 participants |
| Omeprazole | Surgery | 0 participants |
p-value: <0.05Fisher Exact
Other Pre-specified
Duration of Hospital Stay
Time frame: 6wk
Population: intention to treat (ITT)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rabeprazole Sodium | Duration of Hospital Stay | 8.0 days | Standard Deviation 5.6 |
| Omeprazole | Duration of Hospital Stay | 6.7 days | Standard Deviation 2.1 |
p-value: <0.05t-test, 2 sided
Other Pre-specified
Mean Units of Blood Transfusion
In order to compare the total amount of blood transfusion, mean units of blood transfusion was used.
Time frame: day 3
Population: intention to treat (ITT)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rabeprazole Sodium | Mean Units of Blood Transfusion | 1.3 Mean units of blood transfusion | Standard Deviation 1.4 |
| Omeprazole | Mean Units of Blood Transfusion | 1.4 Mean units of blood transfusion | Standard Deviation 1.3 |
p-value: <0.05t-test, 2 sided