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

Br J Surg. 2015 Jul;102(8):894-901. doi: 10.1002/bjs.9824. Epub 2015 May 12.

Abstract

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 39-49 mm 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 2 years. Included patients were treated with 10, 25 or 40 mg pemirolast, or matching placebo for 52 weeks. 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 70·8 years; 88·0 per cent men) were included in the trial. The overall mean growth rate was 2·42 mm 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).

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / therapeutic use*
  • Aortic Aneurysm, Abdominal / diagnostic imaging
  • Aortic Aneurysm, Abdominal / drug therapy*
  • Aortic Aneurysm, Abdominal / pathology*
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Mast Cells / drug effects*
  • Mast Cells / pathology
  • Middle Aged
  • Pyridines / administration & dosage
  • Pyridines / therapeutic use*
  • Pyrimidinones / administration & dosage
  • Pyrimidinones / therapeutic use*
  • Ultrasonography

Substances

  • Anti-Inflammatory Agents
  • Pyridines
  • Pyrimidinones
  • pemirolast

Associated data

  • ClinicalTrials.gov/NCT01354184