A combination of esomeprazole and aspirin reduces tissue concentrations of prostaglandin E(2) in patients with Barrett's esophagus

Abstract

BACKGROUND& AIMS: Proton pump inhibitors and nonsteroidal anti-inflammatory drugs might prevent esophageal adenocarcinoma in patients with Barrett's esophagus (BE), but there are limited data from clinical trials to support this concept. We conducted a randomized, double-blind, placebo-controlled, phase 2 trial to assess the effects of the combination of aspirin (3 different doses) and esomeprazole on tissue concentrations of prostaglandin (PG) E(2) in patients with BE with no dysplasia or low-grade dysplasia.

Methods: Participants were recruited through the multicenter Cancer Prevention Network and randomly assigned to groups that were given 40 mg esomeprazole twice daily in combination with an aspirin placebo once daily (arm A; n = 30), with 81 mg aspirin once daily (arm B; n = 47), or with 325 mg aspirin once daily (arm C; n = 45) for 28 days. We collected esophageal biopsy specimens before and after the intervention period to determine the absolute change in mean concentration of PGE(2) (the primary end point).

Results: Based on data from 114 patients, baseline characteristics were similar among groups. The absolute mean tissue concentration of PGE(2) was reduced by 67.6 ± 229.68 pg/mL in arm A, 123.9 ± 284.0 pg/mL in arm B (P = .10 vs arm A), and 174.9 ± 263.62 pg/mL in arm C (P = .02 vs arm A).

Conclusions: In combination with esomeprazole, short-term administration of higher doses of aspirin, but not lower doses or no aspirin, significantly reduced tissue concentrations of PGE(2) in patients with BE with either no dysplasia or low-grade dysplasia. These data support further evaluation of higher doses of aspirin and esomeprazole to prevent esophageal adenocarcinoma in these patients. Clinical trial registration number NCT00474903.

Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

CONSORT Diagram that shows the number of participants that were pre-registered, the number of screen failures, along with the number of participants that were randomized and evaluable for the primary endpoint.

Figure 2

Boxplots for the Absolute Change in PGE2 by Intervention Arm. After adjusting for the interim analysis and multiple comparisons, the nominal significance level was 0.0247. As shown, the Higher Dose Aspirin + PPI intervention resulted in a significant decrease in PGE2 values as compared to Aspirin Placebo + PPI (p = 0.020), while the Lower Dose Aspirin + PPI intervention did not differ significantly from Aspirin Placebo + PPI (p=0.096).

Figure 3

Boxplots for the Percent Change in PGE2 by Intervention Arm. As shown, the Higher Dose Aspirin + PPI and Lower Dose Aspirin + PPI interventions resulted in significant decreases in PGE2 values as compared to Aspirin Placebo + PPI (p < 0.001).