Plain English Summary
Background and study aims
Low doses of aspirin (LDA) are widely known to have blood clotting effects. However, aspirin does through through suppressing production of molecules called prostaglandins. The reduction in prostaglandins can lead to injury of the intestinal mucosa. Therefore, it is recommended that LDA users also use another type of drug called a proton pump inhibitor (PPI), which can help to prevent this mucosal injury in the upper gastrointestinal tract. PPIs inhibit secretion of stomach acid. However, the inhibition of stomach acid secretion does not prevent mucosal injuries in the small intestine as a result of LDA use. A strategy to prevent LDA-induced injuries in the small intestine has not yet been established. This study aims to investigate whether high doses of ecabet sodium (ES) can be used to prevent LDA-induced small intestinal mucosal injuries.
Who can participate?
Healthy adults aged 20-65
What does the study involve?
Participants will be randomly allocated to group A or group B. Group A will receive 100 mg of LDA to take once daily, whereas group B will receive 100 mg of LDA (once daily) and 4 g of ES (1 g taken 4 times daily). Both groups will be asked to take these for a 2 week period. Participants will undergo small bowel capsule endoscopy (SBCE) before beginning to take the study drugs and after taking the drugs for 2 weeks.
What are the possible benefits and risks of participating?
There are no known benefits to participants taking part in this study. The possible risks of taking part in this study include adverse events associated with administration of LDA or ES, and retaining the capsule endoscope in the body.
Where is the study run from?
Osaka Medical College Hospital (Japan)
When is the study starting and how long is it expected to run for?
December 2009 to March 2012
Who is funding the study?
Second Department of Internal Medicine, Osaka Medical College (Japan)
Who is the main contact?
Kazuhiro Ota
clash_kaz@yahoo.co.jp
Trial website
Contact information
Type
Public
Primary contact
Dr Kazuhiro Ota
ORCID ID
http://orcid.org/0000-0002-5628-9662
Contact details
2-7
Daigaku-machi
Takatsuki
569-8686
Japan
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
UMIN000033984
Study information
Scientific title
Preventive effect of ecabet sodium on low-dose aspirin-induced small intestinal mucosal injury: a randomised, double-blind, pilot study
Acronym
Study hypothesis
Ecabet sodium (ES), a gastric mucoprotective drug that locally acts as an antiulcer agent, has anti-pepsin activity. ES binds to proteins to form a complex that is resistant to the peptic activity of gastric juice, increasing the capacity of the gastric mucosa to synthesize prostaglandin E2 and/or prostacyclin and enhancing gastric mucosal defensive factors, such as mucosal blood flow, mucosal adherent mucus, and mucosal bicarbonate secretion. As these mechanisms share some features with those of rebamipide, we hypothesized that ES might also prevent small intestinal mucosal injury.
Ethics approval
Ethics Review Committee at Osaka Medical College, 18/01/2010, No. 730
Study design
Interventional prospective double-blind pilot randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
No participant information sheet available
Condition
Low-dose aspirin-induced small intestinal mucosal injury
Intervention
Participants were randomly allocated to group A and group B and instructed to take the study drug(s) orally for 2 weeks. A coordinator performed a simple fixed-allocation randomisation using a block-randomization scheme.
Group A received LDA (low-dose aspirin) (100 mg) to take once daily. Group B received LDA to take once daily and 4.0g of ecabet sodium (ES) (1.0 g to be taken 4 times daily, GASTROM® Granules 66.7%, Mitsubishi Tanabe Pharma Corporation, Osaka, Japan). The dosage of LDA for this group was determined on the basis of the dosage recommended for antithrombotic activity in cardiovascular and cerebrovascular diseases. Small bowel capsule endoscopy (SBCE) was performed before and 2 weeks after drug administration.
The total duration of treatment was determined based on previous reports on LDA-induced small intestinal mucosal injury.
Intervention type
Drug
Phase
Not Applicable
Drug names
Ecabet sodium
Low-dose aspirin
Primary outcome measure
Comparison of the severity of small intestinal mucosal injury between baseline and 2 weeks after aspirin administration in each group. Small intestinal lesions were examined using a PillCamSB (Given Imaging, Ltd, Yoquneam, Israel), an SBCE device specifically designed for assessing the small intestine. The SBCE findings were evaluated to identify spotty redness, patchy redness, erosion, and ulcer. In addition, if bleeding or stenosis was detected, these findings were appended to those related to mucosal injuries. A spotty redness was defined as a point, a patchy redness as a red region with a border extending from the peripheral normal mucosa, an erosion as a defect in the normal villus mucosa, and an ulcer as defects covered with a white coat. Two investigators independently assessed the capsule endoscopic images under blinded conditions. If the observers recorded different findings, they discussed the case until an agreement was reached. This was assessed at the baseline and after 2 weeks.
Secondary outcome measures
Comparison of the severity of small intestinal mucosal injury 2 weeks after aspirin administration between group A and group B, assessed as per primary outcome measure.
Overall trial start date
11/12/2009
Overall trial end date
31/03/2012
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Healthy adults
2. Aged 20-65
3. Provided informed consent based on full understanding of the study protocol
4. No history of medication use during the month before enrolment in the study
Participant type
Healthy volunteer
Age group
Adult
Gender
Both
Target number of participants
30
Participant exclusion criteria
1. History of peptic ulcers or gastrointestinal bleeding
2. Significant hepatic, renal, heart or respiratory diseases
3. History of gastrointestinal surgery other than appendectomy
4. Use of any of the following within 2 weeks prior to the study:
4.1. Oral histamine H2-receptor antagonists
4.2. Gastrointestinal kinetic agents
4.3. Gastric mucoprotective drugs
5. Use of any of the following within 4 weeks prior to the study:
5.1. Oral non-steroidal anti-inflammatory drugs (NSAIDs)
5.2. Steroids
5.3. Anticholinergic drugs
5.4. Anticancer drugs
5.5. Antithrombotic drugs
6. Alcohol or chemical dependency
7. History of gastrointestinal obstruction
8. Refusal to consent to surgery that would be required if the capsule endoscope was retained in the body
9. Determination by the investigator, at his/her discretion, that the participant is ineligible for participation in the study for any reason
Recruitment start date
04/10/2011
Recruitment end date
28/12/2011
Locations
Countries of recruitment
Japan
Trial participating centre
Osaka Medical College
2-7, Daigaku-machi
Takatsuki
569-8686
Japan
Funders
Funder type
Not defined
Funder name
Investigator initiated and funded
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Planned publication in a high impact, peer-reviewed journal
IPD sharing statement:
The datasets generated during and/or analysed during the current study are/will be available upon request from clash_kaz@yahoo.co.jp
Intention to publish date
31/03/2013
Participant level data
Available on request
Basic results (scientific)
Publication list
2019 results in https://www.ncbi.nlm.nih.gov/pubmed/30621622 [Added 10/01/2019]