Rebamipide does not protect against naproxen-induced gastric damage: a randomized double-blind controlled trial.
BACKGROUND
Rebamipide is a gastroprotective agent with promising results against gastric damage induced by non-steroidal anti-inflammatory drugs. The present study evaluated if rebamipide protects against naproxen-induced gastric damage in healthy volunteers. Changes in gastric PGE2 tissue concentration were also evaluated.


METHODS
After a preliminary endoscopy to rule out previous gastric macroscopic damage, twenty-four healthy volunteers of both sexes were divided into 2 groups. One group received sodium naproxen 550 mg b.i.d. plus placebo for 7 days, while the other group received sodium naproxen 550 mg b.i.d. plus rebamipide 100 mg b.i.d. At the end of treatment, a new endoscopy was performed. Gastric macroscopic damage was evaluated by the Cryer score and by the modified Lanza score. The primary outcome measure of the trial was the macroscopic damage observed in each treatment group at the end of treatment. Biopsies were collected at both endoscopies for PGE2 quantification and histopathological analysis (secondary outcomes). Tissue PGE2 was quantified by ELISA. The randomization sequence was generated using 3 blocks of 8 subjects each. Volunteers and endoscopists were blind to whether they were receiving rebamipide or placebo.


RESULTS
All recruited volunteers completed the trial. Sodium naproxen induced gastric damage in both groups. At the end of the study, median Cryer score was 4 in both groups (Difference = 0; 95%CI = -1 to 0; p = 0.728). In the placebo group, the mean tissue PGE2 concentration was 1005 ± 129 pg/mL before treatment and 241 ± 41 pg/mL after treatment (p < 0.001). In the rebamipide group, the mean tissue PGE2 concentration was 999 ± 109 pg/mL before treatment, and 168 ± 13 pg/mL after treatment (p < 0.001). There was no difference in mean tissue PGE2 between the two groups (difference = 5; 95%CI from -334.870 to 345.650; p = 0.975). No significant change was observed at the histopathological evaluation, despite the evident macroscopic damage induced by naproxen.


CONCLUSIONS
Rebamipide does not protect against naproxen-induced gastric damage in healthy volunteers.


BACKGROUND
ClinicalTrials.gov, NCT02632812 . Registered 14 December 2015.
Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro (UFRJ), 21941-902, Rio de Janeiro, Brazil. thiagogagliano@gmail.com.
Thiago
T
Gagliano-Jucá
Galeno Research Unit, Campinas, Brazil; Faculty of Medical Sciences, Metropolitan University of Santos, Santos, Brazil.
Ronilson A
RA
Moreno
Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, Brazil.
Tiago
T
Zaminelli
Department of Pharmacology, ICB - University of Sao Paulo (USP), 05508-900, Sao Paulo, Brazil.
Mauro
M
Napolitano
Department of Gastroenterology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, Brazil.
Antônio Frederico N
AF
Magalhães
Brazilian Society for Digestive Endoscopy (SOBED), Sao Paulo, Brazil.
Aloísio
A
Carvalhaes
Department of Gastroenterology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, Brazil.
Miriam S
MS
Trevisan
Unicastelo Medical School, University Camilo Castelo Branco (UNICASTELO), Fernandopolis, Brazil.
John L
JL
Wallace
Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, Brazil.|Unicastelo Medical School, University Camilo Castelo Branco (UNICASTELO), Fernandopolis, Brazil.|Department of Pharmacology, ICB - University of Sao Paulo (USP), Sao Paulo, Brazil.
Gilberto
G
De Nucci
D000293:Adolescent; D000328:Adult; D000409:Alanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D015232:Dinoprostone / Q000032:analysis; D004311:Double-Blind Method; D005260:Female; D005753:Gastric Mucosa / Q000473:pathology; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009288:Naproxen / Q000009:adverse effects*; D015363:Quinolones / Q000627:therapeutic use*; D013272:Stomach Diseases / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D055815:Young Adult
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005765:Gastrointestinal Agents; D015363:Quinolones; D009288:Naproxen; D015232:Dinoprostone; C052785:rebamipide; D000409:Alanine
Cryer score; ELISA; Endoscopy; Histopathology; Human; Modified Lanza score; NSAID