Effects of Oral Rabeprazole on the Prevention of Ulcer Bleeding Following Endoscopic Mucosal Resection

Sponsor

The Catholic University of Korea (Other)

Overall Status

Completed

CT.gov ID

NCT00844675

Collaborator

Janssen Korea, Ltd., Korea (Industry)

120

Enrollment

Location

Arms

Duration (Months)

2.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is:

To examine if oral administration of Pariet (proton pump inhibitor, 20mg tablets, twice daily for 5 days) before Endoscopic mucosal resection(EMR) exhibits preventive effects of ulcer bleeding compared with placebo group (preoperative administration of placebo)
To evaluate the effects on the suppression of acid secretion of preoperative administration of an Proton pump inhibitor

Condition or Disease	Intervention/Treatment	Phase
Early Gastric Adenocarcinoma Adenocarcinoma, Tubular	Drug: rabeprazole Drug: placebo	Phase 4

Detailed Description

Endoscopic mucosal resection (EMR) is less invasive than surgery and is known to be general treatment for early gastric cancer or gastric adenoma when patients' quality of life is taken into consideration. However, major complications such as bleeding and perforation remain to be problematic.1-5 The incidence of these complications is expected to rise as the size of lesions for which EMR is indicated has enlarged. Histamine 2 receptor antagonists (H2RA) and proton pump inhibitors (PPI) have been used for the bleeding,1-3 but the bleeding rate following EMR has been reported to be still high as 1.4% to 24%.1,4 Green et al and Berstad et al cited in their research that intragastric PH should be sustained above 5.4 to prevent bleeding, and PPIs should be administered instead of H2RAs to keep PH above 5.4. Being studied are administration modalities to enhance the therapeutic efficacy of PPIs or H2RAs.1-3 Several studies have already demonstrated that high-dose PPI therapy, for which a PPI was administered twice daily, effectively blocks acid secretion by increasing intragastric pH to neutral.3 Our study team also suggested in a previous study that high-dose PPI therapy was adequate to maintain intragastric pH above 6.
PPIs are known to induce the suppression of acid secretion because they destroy a proton pump, yet it takes 5 days to achieve their maximum effects.7,8 It's been suggested that the onset of PPIs is slow to prevent bleeding with administration of a PPI after EMR.4 Therefore, our investigators expect that 5-day administration of an oral PPI before EMR would increase intragastric pH to above 6 and would be at least equal to or superior to intravenous PPIs currently being used in terms of the suppression of acid secretion.
This is a prospective, randomized, comparative study to substantiate that oral administration of rabeprazole (Pariet tablets) 20mg twice daily before and after EMR (PO RBP group) will show similar effects on the prevention of bleeding compared with the conventional treatment with iv administration of pantoprazole after EMR but no special medication given before EMR (Placebo group). In addition, we are going to measure intragastric pH among part of study subjects and then to evaluate if the effect of acid suppression in the PO RBP group is superior to that in the placebo group.

Study Design

Study Type:

Interventional

Actual Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Prevention

Official Title:

Effects of Preoperative Administration of Oral Rabeprazole on the Prevention of Ulcer Bleeding Following Endoscopic Mucosal Resection(EMR): Prospective, Randomized, Placebo-controlled, Comparative Study

Study Start Date :

Oct 1, 2007

Actual Primary Completion Date :

Dec 1, 2011

Actual Study Completion Date :

Mar 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: rabeprazole rabeprazole	Drug: rabeprazole The rabeprazole group will receive oral rabeprazole 20mg twice day (morning and evening) 30 minutes before meals from 5 days before EMR (D-5) to 1 day before EMR (D-1). Other Names: Pariet(rabeprazole)
Experimental: placebo placebo	Drug: placebo The placebo group will receive a placebo by mouth twice a day (morning and evening) 30 minutes before meals from 5 days before EMR (D-5) to 1 day before EMR (D-1).

Arm

Intervention/Treatment

Experimental: rabeprazole

rabeprazole

Drug: rabeprazole

The rabeprazole group will receive oral rabeprazole 20mg twice day (morning and evening) 30 minutes before meals from 5 days before EMR (D-5) to 1 day before EMR (D-1).

Other Names:

Pariet(rabeprazole)

Experimental: placebo

placebo

Drug: placebo

The placebo group will receive a placebo by mouth twice a day (morning and evening) 30 minutes before meals from 5 days before EMR (D-5) to 1 day before EMR (D-1).

Outcome Measures

Primary Outcome Measures

Frequency of bleeding after EMR is performed [4weeks]

Secondary Outcome Measures

Number (No./cm2) of visible vessels on the fundus of ulcer on endoscopy performed within 24 hours after EMR [day 1]
Percentage of a pH change with intragastric pH greater than 6 in 24 hours after EMR [day 0]
Measurement of a change in the size of ulcer [4weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients who have EMR planned as well as meet the criteria described below will be selected as study subjects
Patients in whom EMR is indicated:

Gastric adenoma
Early gastric adenocarcinoma

Moderately or well differentiated adenocarcinoma
Gastric cancer limited to only mucosa on endoscopic ultrasonography
No invasion of lymph nodes or metastases (diagnosed by CT)

EMR to be performed for other diagnostic purposes

Women of child-bearing potential should avoid pregnancy
Subjects who consented to a EMR procedure in writing

Exclusion Criteria:

Patients who meet the criteria described below should be excluded from study subjects:

Younger than 18 years old
Patients with a history of upper gastrointestinal surgery or vagotomy
Patients with serious adverse reactions secondary to cardiac, renal, hepatic, or hematologic diseases (e.g. creatinine> 2.5 mg/dl, total bilirubin >3.0 mg/dl)
Patients with diseases that may have a great impact on the clinical study
Patients to whom the stimulation of gastrointestinal movement poses risks as in gastrointestinal bleeding, mechanical ileus and perforation
Women who are pregnant or nursing
Patients who are being treated with adrenocorticoid steroids, nonsteroidal anti-inflammatory drugs including aspirin, or other ulcer inducers
Patients who are taking other antiulcer drugs (antacids, antihistamines, etc) that may affect the efficacy assessments of the study drug (but, except for patients not taking the drugs over 7 days)
Patients with severe psychiatric diseases
Patients who received other investigational drugs within 30 days prior to the start of this study or who are currently participating in other clinical study
Patients who did not consent to the clinical study
Patients who can not be examined