A Study to Evaluate REbamiPide as an Adjuvant Regimen to Heal erosIve Reflux Esophagitis

Gastroesophageal Reflux Clinical Trial

— REPAIR  

Official title:

A Multicenter, Randomized, Double-blinded, Placebo-controlled Pilot Study to Evaluate the Efficacy and Safety of Rebamipide as an Adjuvant Regimen to Heal erosIve Reflux Esophagitis (REPAIR)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02755753
• Other study ID #: 037-OTC-1201i
• Status: Completed
• Phase: Phase 4
• First received: September 2, 2015
• Last updated: April 26, 2016
• Start date: January 2014
• Est. completion date: April 2016

Study information

• Verified date: April 2016
• Source: Severance Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Ministry of Food and Drug Safety
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate whether Rebamipide facilitate the healing of inflamed mucosa as an adjuvant regimen in erosive reflux esophagitis (ERE).

Description:

1. To evaluate whether Rebamipide facilitate the healing of inflamed mucosa as an adjuvant regimen in erosive reflux esophagitis patients

2. To evaluate the safety of rebamipide as an adjuvant regimen in erosive reflux esophagitis (ERE)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 143
• Est. completion date: April 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Male/female patients aged 20 to 70 at the time of writing an informed consent.

2. Subjects who were diagnosed with Erosive Reflux Esophagitis (ERE) using Los Angeles (LA) classification grade A~D, confirmed by endoscopy.

3. The subjects regardless of presence of ERE symptom (i.e., symptomatic ERE or asymptomatic ERE).

For symptomatic ERE, the subject must have one or more symptoms of the followings:

acid regurgitation, heartburn, epigastric pain, cough, hoarseness, globus pharyngis, atypical chest pain.

4. Subjects who have consented to participate in this clinical study by signing an informed consent form.

Exclusion Criteria:

1. Patients with known hypersensitivity to any component of Lanston® and/or Mucosta® formulations.

2. Other concurrent organic upper gastroesophageal disease in endoscopy (i.e., drug-induced esophagitis, viral esophagitis, Mallory-Weiss syndrome, peptic ulcer disease, malignancies) and patients who was diagnosed with Barrett's esophagus.

3. History of abdominal surgery that can affect gastrointestinal motility (except appendectomy and hysterectomy).

4. History of upper gastrointestinal bleeding or obstruction.

5. Patients administrated with any drugs that can affect the efficacy of study regimen (proton pump inhibitors, revaprazan, prokinetics, H2-blockers, etc.) within 2 weeks (however, 4 weeks for PPIs) prior to enrollment and/or those who are required of NSAIDs, anti-coagulants, anti-cholinergics, prostaglandin E, corticosteroids, and anti-depressants treatment during the study period.

6. History of pancreatobiliary disease (except asymptomatic gallbladder stone), inflammatory bowel disease, cirrhotic liver disease, chronic kidney disease.

7. Pregnant, nursing, and childbearing potential women who is unwilling to effective contraception; for example, oral contraceptives, hormonal methods, placement of an intrauterine device (IUD) or intrauterine system (IUS), barrier methods (i.e., condom or occlusive cap with spermicidal foam/gel/film/cream/suppository), male sterilization, and true abstinence.

8. History of psychological disorder, alcoholics, and drug abuser.

9. Blood test results of hemoglobin (Hb) = 10.0 g/dL, platelets = 50,000 /µL, total WBCs = 4,000/µL or = 10,000/µL, and with serum test results showing the levels of AST, ALT, ALP, BUN, and creatinine exceeding twice the normal range of respective institution.

10. Patients who previously underwent another clinical survey within 4 weeks.

11. History of major medical disease that can affect general condition and other patients deemed not eligible for this study by investigators.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Esophagitis
• Esophagitis, Peptic
• Gastroesophageal Reflux

Intervention

Drug:
• Lansoprazole
Oral administration of Lanston® (lansoprazole) 30 mg, 1 capsule, PO, qd, 30 min before breakfast
• Rebamipide
Oral administration of Mucosta (rebamipide) 100 mg, 1 tablet, PO, tid, 30 minutes before breakfast, lunch, and dinner
• Rebamipide-placebo
Oral administration of Mucosta®-placebo, 1 tablet, PO, tid, 30 minutes before breakfast, lunch and dinner

Locations

Country	Name	City	State
China	Yang Shiming	Chongqing	Chongqing
Korea, Republic of	Soonchunhyang University Bucheon Hospital	Bucheon
Korea, Republic of	Kyungpook National University Medical Center	Daegu
Korea, Republic of	Konyang University Hospital	Daejeon
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul

Sponsors (2)

Lead Sponsor	Collaborator
YongChan Lee	Otsuka Pharmaceutical Co., Ltd.

Countries where clinical trial is conducted

China,  Korea, Republic of, 

References & Publications (24)

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Hatlebakk JG, Berstad A. Lansoprazole 15 and 30 mg daily in maintaining healing and symptom relief in patients with reflux oesophagitis. Aliment Pharmacol Ther. 1997 Apr;11(2):365-72. — View Citation

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Kang JY. Systematic review: geographical and ethnic differences in gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2004 Oct 1;20(7):705-17. Review. — View Citation

Kim BJ, Cheon WS, Oh HC, Kim JW, Park JD, Kim JG. Prevalence and risk factor of erosive esophagitis observed in Korean National Cancer Screening Program. J Korean Med Sci. 2011 May;26(5):642-6. doi: 10.3346/jkms.2011.26.5.642. Epub 2011 Apr 21. — View Citation

Kim KM, Cho YK, Bae SJ, Kim DS, Shim KN, Kim JH, Jung SW, Kim N. Prevalence of gastroesophageal reflux disease in Korea and associated health-care utilization: a national population-based study. J Gastroenterol Hepatol. 2012 Apr;27(4):741-5. doi: 10.1111/j.1440-1746.2011.06921.x. — View Citation

Kovacs TO, Freston JW, Haber MM, Atkinson S, Hunt B, Peura DA. Long-term quality of life improvement in subjects with healed erosive esophagitis: treatment with lansoprazole. Dig Dis Sci. 2010 May;55(5):1325-36. doi: 10.1007/s10620-009-0871-8. Epub 2009 Jul 7. — View Citation

Kovacs TO, Freston JW, Haber MM, Hunt B, Atkinson S, Peura DA. Long-term efficacy of lansoprazole in preventing relapse of erosive reflux esophagitis. Dig Dis Sci. 2009 Aug;54(8):1693-701. doi: 10.1007/s10620-009-0769-5. Epub 2009 Mar 7. — View Citation

Kusano M, Ino K, Yamada T, Kawamura O, Toki M, Ohwada T, Kikuchi K, Shirota T, Kimura M, Miyazaki M, Nakamura K, Igarashi S, Tomizawa M, Tamura T, Sekiguchi T, Mori M. Interobserver and intraobserver variation in endoscopic assessment of GERD using the "Los Angeles" classification. Gastrointest Endosc. 1999 Jun;49(6):700-4. — View Citation

Lancaster GA, Dodd S, Williamson PR. Design and analysis of pilot studies: recommendations for good practice. J Eval Clin Pract. 2004 May;10(2):307-12. — View Citation

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Lee SJ, Song CW, Jeen YT, Chun HJ, Lee HS, Um SH, Lee SW, Choi JH, Kim CD, Ryu HS, Hyun JH. Prevalence of endoscopic reflux esophagitis among Koreans. J Gastroenterol Hepatol. 2001 Apr;16(4):373-6. — View Citation

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Song JH, Chung SJ, Lee JH, Kim YH, Chang DK, Son HJ, Kim JJ, Rhee JC, Rhee PL. Relationship between gastroesophageal reflux symptoms and dietary factors in Korea. J Neurogastroenterol Motil. 2011 Jan;17(1):54-60. doi: 10.5056/jnm.2011.17.1.54. Epub 2011 Jan 26. — View Citation

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Wong RK, Yeoh KG, Gwee KA, Tay HW, Ho KY. Validation of structured scoring using the LA classification for esophagitis and endoscopically suspected Barrett's esophagus in a tertiary Asian endoscopy center. J Gastroenterol Hepatol. 2009 Jan;24(1):103-6. doi: 10.1111/j.1440-1746.2008.05680.x. Epub 2008 Dec 1. — View Citation

Yoshida N, Kamada K, Tomatsuri N, Suzuki T, Takagi T, Ichikawa H, Yoshikawa T. Management of recurrence of symptoms of gastroesophageal reflux disease: synergistic effect of rebamipide with 15 mg lansoprazole. Dig Dis Sci. 2010 Dec;55(12):3393-8. doi: 10.1007/s10620-010-1166-9. Epub 2010 Mar 3. — View Citation

* Note: There are 24 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Endoscopic healing rate	The ratio of the endoscopically completely healed (normal or minimal change) patients per groups	4 weeks	No
Secondary	Histologic change	Histologic change defined with Hematoxylin and eosin (H&E) stain	4 weeks	No
Secondary	Change in inflammatory cytokines	Change in the tissue level of Platelet activating factor (PAF) and Interleukin-8 (IL-8)	4 weeks	No
Secondary	Time to complete symptom relief	Interval between inital medication and the first time of symptom relief judged by subject's diary	every 2 week, up to 4 week	No
Secondary	Overall symptom relief	The proportion of relieved subjects at the end of treatment	every 2 week, up to 4 week	No
Secondary	Adverse events profile	patient's symptoms, physical findings, abnormal laboratory values, vital signs, and ECG findings	every 2 week, up to 4week	Yes