Clinical trial: the incidence of NSAID-associated endoscopic gastric ulcers in patients treated with PN 400 (naproxen plus esomeprazole magnesium) vs. enteric-coated naproxen alone.
BACKGROUND
Gastroprotective co-therapy may reduce the risk of nonsteroidal anti-inflammatory drug (NSAID)-associated gastric ulcers, but adherence is suboptimal.


OBJECTIVE
To compare the incidence of gastric ulcers with PN 400 [enteric-coated (EC) naproxen 500 mg and immediate-release esomeprazole 20 mg], or EC naproxen.


METHODS
Two randomized, double-blind, multicentre studies (PN400-301, PN400-302). Patients [stratified by low-dose aspirin (< or =325 mg) use] aged > or =50 years or 18-49 years with a history of ulcer, received PN 400 BID (301, n = 218; 302, n = 210) or EC naproxen 500 mg BID (301, n = 216; 302, n = 210) for 6 months. The primary endpoint was the cumulative incidence of endoscopic gastric ulcers.


RESULTS
The cumulative incidence of gastric ulcers was significantly lower with PN 400 vs. EC naproxen (301: 4.1% vs. 23.1%, P < 0.001; 302: 7.1% vs. 24.3%, P < 0.001). PN 400 was associated with a lower combined incidence of gastric ulcers vs. EC naproxen in low-dose aspirin users (n = 201) (3.0% vs. 28.4%, P < 0.001) and non-users (n = 653) (6.4% vs. 22.2%, P < 0.001). The incidence of, and discontinuations due to, upper gastrointestinal (UGI) AEs was significantly lower with PN 400 relative to EC naproxen (P < 0.01, both studies).


CONCLUSIONS
PN 400 significantly reduces the incidence of gastric ulcers, regardless of low-dose aspirin use, in at-risk patients, and is associated with improved UGI tolerability relative to EC naproxen (ClinicalTrials.gov, NCT00527782).
Goldstein
J L
JL
Department of Medicine, University of Illinois at Chicago, 60612, USA. jlgoldst@uic.edu
Hochberg
M C
MC
Fort
J G
JG
Zhang
Y
Y
Hwang
C
C
Sostek
M
M
D000293:Adolescent; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D004311:Double-Blind Method; D064098:Esomeprazole / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D015994:Incidence; D008274:Magnesium / Q000627:therapeutic use; D008875:Middle Aged; D009288:Naproxen / Q000008:administration & dosage / Q000009:adverse effects*; D010003:Osteoarthritis / Q000188:drug therapy*; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000188:drug therapy; D013608:Tablets, Enteric-Coated; D016896:Treatment Outcome; D055815:Young Adult
D000894:Anti-Inflammatory Agents, Non-Steroidal; D013608:Tablets, Enteric-Coated; D009288:Naproxen; D008274:Magnesium; D064098:Esomeprazole