A total of 28 departments were included and randomized 1:1 using a computer generated list. The sample size calculation was based on an average cluster size of 1,611 patients. We estimated the average cluster size in the DIFFICAIR trial to approximately 2,500 patients, giving a total of 70,000 included patients during the trial period. The enhanced sample size allows for a potentially slight loss of clusters according to the power calculation, from 30 to potentially 26. Our sample size estimation might be of a conservative nature, calling for more clusters than necessary[22].