Compare the Effect of Eupatilin and Rebamipide on the Prevention of Gastroenteropathy (CEERS)

Compare the Effect of Eupatilin and Rebamipide on the Prevention of Gastroenteropathy in Patients With NSAIDs and Low Dose Steroid: A Single-center, Randomized, Open Labeled, Pilot Study

The purpose of this study is to evaluate the efficacy of eupatilin on the prevention of gastroenteropathy in patients with NSAIDs and low dose steroid by comparing with rebamipide.

Study Overview

• Status: Not yet recruiting
• Conditions: Osteoarthritis; Rheumatoid Arthritis; Enteritis; Gastric Ulcer; Ankylosing Spondylitis; Other Musculoskeletal Disorder; NSAID-Associated Gastropathy; NSAID (Non-Steroidal Anti-Inflammatory Drug) Induced Enteropathy
• Intervention / Treatment: Drug: Eupatilin; Drug: Rebamipide

Detailed Description

After being informed of the study and potential risks, all patients giving written informed consents will undergo a 1-week screening period to determine eligibility for study entry. During screening period, patients will undergo fecal calprotectin test, upper endoscopy and submit symptom diary. At week 0, subjects who meet the eligibility criteria will be randomized in a open labeled manner in 1:1 ratio to eupatilin (90mg twice daily-test group, 25 patients) or rebamipide (100mg three times daily-control group paients) for 8 weeks. At week 8, subjects undergo fecal calprotectin test, upper endoscopy and submit symptom diary.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Men and women who were adults at the time of receipt of written consent (age 19-70)
2. Those with rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, or other musculoskeletal diseases that require continuous administration of nonsteroidal anti-inflammatory drugs (NSAIDs) and oral steroids for more than 8 weeks.
3. At screening (before baseline) endoscopy results Modified Lanza Score (MLS) 0~2
4. Those who have not had severe gastrointestinal symptoms in the previous 3 months[Excluding mild abdominal distention, abdominal pain, diarrhea, dyspepsia, nausea, and vomiting]
5. A person who agrees to participate in this clinical trial and voluntarily signs a written consent form

Exclusion Criteria:

1. Those with a history of gastrointestinal surgery (excluding appendectomy)
2. Those who have a history of esophageal cancer, liver cancer, pancreatic cancer, gastric cancer, colon cancer, small intestine tumor or other malignant disease within 5 years from the time of screening
3. Gastrointestinal diseases that are clinically significant by upper gastrointestinal endoscopy, namely active peptic ulcer, reflux esophagitis, gastroesophageal varices, Barrett's esophagus, Barrett's esophagitis, esophageal stenosis, inflammatory bowel disease (Those diagnosed with inflammatory bowel disease, IBD), gastrointestinal bleeding, etc.
4. Those with a history of recurrent gastrointestinal ulcer/perforation
5. Those with cerebrovascular bleeding or confirmed systemic bleeding disorder
6. Persons with severe uncontrolled heart failure (NYHA Class III-IV), high blood pressure (above 160/100 mmHg)
7. Those who have plans for surgical operation during the clinical trial period
8. Persons with a history of chronic pancreatitis, chronic renal diseases, chronic liver diseases, or other serious comorbid diseases
9. Those with clinically significant abnormal values (AST, ALT, BUN, Cr exceeding 2.5 times or Hb<10g/dL) by laboratory examination
10. Those with a history of alcohol or drug abuse/dependence
11. Pregnant and lactating women
12. Those who participated in other clinical trials within 30 days prior to participation in this clinical trial and received investigational drugs or received procedures
13. Patients who are difficult to perform this clinical trial by other investigators or who are judged to have medical findings that are not suitable for the clinical trial
14. Those who received celecoxib and prednisolone (or methylprednisolone) within 30 days prior to participation in this clinical trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: eupatilin; take eupatilin to prevent NSAID induced gastroenteropathy	Drug: Eupatilin; take eupatilin to prevent NSAID induced gastroenteropathy
Active Comparator: rebamipide; take rebamipide to prevent NSAID induced gastroenteropathy	Drug: Rebamipide; take rebamipide to prevent NSAID induced gastroenteropathy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients with gastric damage	Percentage of patients with endoscopic Modified Lanza Score >3	evaluated at day 56

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of gastric erosion number	Change of gastric erosion number at day 56 compared with that at day 0	evaluated at day 0 and day 56
Change of Modified Lanza Score	Change of Modified Lanza Score at day 56 compared with that at day 0	evaluated at 0 day and day 56
Change of duodenal erosion number	Change of duodenal erosion number at day 56 compared with that at day 0	evaluated at day 0 and day 56
Gastrointestinal symptom	Gastrointestinal symptom change using survey at day 56 compared with that at day 0	evaluated at day 0 and day 56
Fecal calprotectin	Fecal calprotectin level change at visit 3 compared with visit 0	evaluated at day 0 and day 56
Antioxidant gene expression	Antioxidant gene expression change at day 56 compared with that at day 0	evaluated at day 0 and day 56

Collaborators and Investigators

• Sponsor: Seoul National University Boramae Hospital
• Collaborators: Dong-A ST Co., Ltd.

Publications and helpful links

General Publications

• Sperling RL. NSAIDs. Home Healthc Nurse. 2001 Nov;19(11):687-9. doi: 10.1097/00004045-200111000-00011. No abstract available.
• Conaghan PG. A turbulent decade for NSAIDs: update on current concepts of classification, epidemiology, comparative efficacy, and toxicity. Rheumatol Int. 2012 Jun;32(6):1491-502. doi: 10.1007/s00296-011-2263-6. Epub 2011 Dec 23.
• MacDonald TM. Epidemiology and pharmacoeconomic implications of non-steroidal anti-inflammatory drug-associated gastrointestinal toxicity. Rheumatology (Oxford). 2000 Dec;39 Suppl 2:13-20; discussion 57-9. doi: 10.1093/rheumatology/39.suppl_2.13.
• Lee SH, Han CD, Yang IH, Ha CW. Prescription pattern of NSAIDs and the prevalence of NSAID-induced gastrointestinal risk factors of orthopaedic patients in clinical practice in Korea. J Korean Med Sci. 2011 Apr;26(4):561-7. doi: 10.3346/jkms.2011.26.4.561. Epub 2011 Mar 28.
• Shim KN, Kim JI, Kim N, Kim SG, Jo YJ, Hong SJ, Shin JE, Kim GH, Park KS, Choi SC, Kwon JG, Kim JH, Kim HJ, Kim JW. The efficacy and safety of irsogladine maleate in nonsteroidal anti-inflammatory drug or aspirin-induced peptic ulcer and gastritis. Korean J Intern Med. 2019 Sep;34(5):1008-1021. doi: 10.3904/kjim.2017.370. Epub 2018 Jun 1.
• Julious S. Sample size of 12 per group rule of thumb for a pilot study. Pharmaceut Statist. 2005;4:287-291.
• Kim HK, Kim JI, Kim JK, Han JY, Park SH, Choi KY, Chung IS. Preventive effects of rebamipide on NSAID-induced gastric mucosal injury and reduction of gastric mucosal blood flow in healthy volunteers. Dig Dis Sci. 2007 Aug;52(8):1776-82. doi: 10.1007/s10620-006-9367-y. Epub 2007 Apr 5.

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2021
• Primary Completion (Anticipated): December 31, 2021
• Study Completion (Anticipated): January 31, 2022

Study Registration Dates

• First Submitted: April 26, 2021
• First Submitted That Met QC Criteria: May 7, 2021
• First Posted (Actual): May 13, 2021

Study Record Updates

• Last Update Posted (Actual): May 13, 2021
• Last Update Submitted That Met QC Criteria: May 7, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Infections; Gastrointestinal Diseases; Stomach Diseases; Joint Diseases; Gastroenteritis; Arthritis; Intestinal Diseases; Spinal Diseases; Bone Diseases; Peptic Ulcer; Duodenal Diseases; Spondylarthropathies; Spondylarthritis; Bone Diseases, Infectious; Ankylosis; Enteritis; Musculoskeletal Diseases; Stomach Ulcer; Spondylitis; Spondylitis, Ankylosing; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Protective Agents; Anti-Ulcer Agents; Antioxidants; Rebamipide
• Other Study ID Numbers: Eupatilin_GEP_01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No