Randomized clinical trial of mast cell inhibition in patients with a medium-sized abdominal aortic aneurysm

TY - JOUR

T1 - Randomized clinical trial of mast cell inhibition in patients with a medium-sized abdominal aortic aneurysm

AU - Sillesen, H

AU - Eldrup, N

AU - Hultgren, R

AU - Lindeman, J

AU - Bredahl, K

AU - Thompson, M

AU - Wanhainen, A

AU - Wingren, U

AU - Swedenborg, J

AU - AORTA Trial Investigators

N1 - © 2015 BJS Society Ltd Published by John Wiley & Sons Ltd.

PY - 2015/7/1

Y1 - 2015/7/1

N2 - Background Abdominal aortic aneurysm (AAA) is thought to develop as a result of inflammatory processes in the aortic wall. In particular, mast cells are believed to play a central role. The AORTA trial was undertaken to investigate whether the mast cell inhibitor, pemirolast, could retard the growth of medium-sized AAAs. In preclinical and clinical trials, pemirolast has been shown to inhibit antigen-induced allergic reactions. Methods Inclusion criteria for the trial were patients with an AAA of 39-49mm in diameter on ultrasound imaging. Among exclusion criteria were previous aortic surgery, diabetes mellitus, and severe concomitant disease with a life expectancy of less than 2years. Included patients were treated with 10, 25 or 40mg pemirolast, or matching placebo for 52weeks. The primary endpoint was change in aortic diameter as measured from leading edge adventitia at the anterior wall to leading edge adventitia at the posterior wall in systole. All ultrasound scans were read in a central imaging laboratory. Results Some 326 patients (mean age 70·8years; 88·0 per cent men) were included in the trial. The overall mean growth rate was 2·42mm during the 12-month study. There was no statistically significant difference in growth between patients receiving placebo and those in the three dose groups of pemirolast. Similarly, there were no differences in adverse events. Conclusion Treatment with pemirolast did not retard the growth of medium-sized AAAs. Registration number: NCT01354184 (https://www.clinicaltrials.gov).

AB - Background Abdominal aortic aneurysm (AAA) is thought to develop as a result of inflammatory processes in the aortic wall. In particular, mast cells are believed to play a central role. The AORTA trial was undertaken to investigate whether the mast cell inhibitor, pemirolast, could retard the growth of medium-sized AAAs. In preclinical and clinical trials, pemirolast has been shown to inhibit antigen-induced allergic reactions. Methods Inclusion criteria for the trial were patients with an AAA of 39-49mm in diameter on ultrasound imaging. Among exclusion criteria were previous aortic surgery, diabetes mellitus, and severe concomitant disease with a life expectancy of less than 2years. Included patients were treated with 10, 25 or 40mg pemirolast, or matching placebo for 52weeks. The primary endpoint was change in aortic diameter as measured from leading edge adventitia at the anterior wall to leading edge adventitia at the posterior wall in systole. All ultrasound scans were read in a central imaging laboratory. Results Some 326 patients (mean age 70·8years; 88·0 per cent men) were included in the trial. The overall mean growth rate was 2·42mm during the 12-month study. There was no statistically significant difference in growth between patients receiving placebo and those in the three dose groups of pemirolast. Similarly, there were no differences in adverse events. Conclusion Treatment with pemirolast did not retard the growth of medium-sized AAAs. Registration number: NCT01354184 (https://www.clinicaltrials.gov).

KW - Aged

KW - Aged, 80 and over

KW - Anti-Inflammatory Agents

KW - Aortic Aneurysm, Abdominal

KW - Double-Blind Method

KW - Female

KW - Humans

KW - Male

KW - Mast Cells

KW - Middle Aged

KW - Pyridines

KW - Pyrimidinones

U2 - 10.1002/bjs.9824

DO - 10.1002/bjs.9824

M3 - Journal article

C2 - 25963302

SN - 0007-1323

VL - 102

SP - 894

EP - 901

JO - British Journal of Surgery

JF - British Journal of Surgery

IS - 8

ER -