Study design and treatments

HESTIA2 was a phase IIb, randomised, double‐blind, double‐dummy, parallel‐group, multicentre study (Fig 1). Participants were randomised 1:1:1 to receive ticagrelor 10, 45 mg or placebo bid, respectively. Randomisation was performed using an interactive voice response system/interactive web response system.

Study design. bid, twice daily; DB, double blind; R, randomisation; V, visit.

The study consisted of three periods over 18 weeks (Fig 1): a 4‐week, single‐blind placebo run‐in period for baseline assessments of pain‐related variables; then a 12‐week, double‐blind treatment period; and a 2‐week follow‐up period after treatment completion.

Randomised patients received one of three regimens, receiving one tablet bid (orally) from each bottle to preserve blinding (double‐dummy): ticagrelor 10 mg plus matching placebo for ticagrelor 45 mg; ticagrelor 45 mg plus matching placebo for ticagrelor 10 mg; matching placebo for ticagrelor 10 and 45 mg.

Study visits occurred at screening/enrolment, at randomisation and thereafter at 1 week, 4 and 12 weeks (end of treatment). A follow‐up phone call was scheduled 2 weeks after the last intake of study drug to collect adverse events (AEs) and any changes in concomitant mediations.

All patients provided written, informed consent before any study‐specific procedures. At each site, the final study protocol, amendments, and informed consent documentation were approved by an Ethics Committee and/or Institutional Review Board, or national regulatory authorities. The study was conducted in accordance with the Declaration of Helsinki and the International Conference on Harmonization/Good Clinical Practice Guidelines, and followed applicable regulatory requirements and AstraZeneca's policy on bioethics.