Lisette van Dam

MRI for diagnosis of recurrent ipsilateral DVT 2 19 least one filling defect in the pulmonary artery tree and if PE was judged to be a probable cause of unexplained death unless proven otherwise by autopsy. An independent committee, who were blinded for all diagnostic procedures and treatment decisions at baseline, assessed and adjudicated all suspected cases of VTE and deaths that occurred during follow-up. After study initiation we observed a relevant prevalence of patients with a MRDTI negative for DVT but positive for superficial thrombophlebitis. These patients were not anticipated in the protocol and were mostly treated with half-therapeutic dose of anticoagulants for six weeks as per local guidelines. Since patients who are treated with anticoagulants have a lower risk to develop a recurrent DVT during follow-up, the primary outcome was modified by adding an additional subgroup: patients with MRDTI negative for both DVT and thrombophlebitis off anticoagulant treatment at inclusion. The main secondary outcome was the interobserver agreement of MRDTI in daily clinical practice. This was assessed post-hoc: the first 10 scans of each study site were re-assessed by the expert team in the LUMC, blinded to the clinical presentation and follow-up of the study patients. Their ruling was compared to the ruling of the attending local radiologist at the moment of clinical presentation. Also, we assessed the feasibility of MRDTI, i.e. the number of patients who could not be included due to MRDTI unavailability as well as the median time between study inclusion and MRDTI scanning. Statistical analysis We aimed to mirror the risk of false-negative test ruling by MRDTI to that of ruling by CUS. In the 2012 ACCP guidelines, the upper limit of the 95% confidence interval (95%CI) of the risk of a false negative serial CUS result in suspected recurrent ipsilateral DVT was estimated to be 6.5% in the setting of a 15% DVT prevalence. 9 In the largest relevant published study, the overall diagnostic failure rate of normal ultrasound findings compared to a reference CUS was 3.3% (5/153, 95%CI 1.2-7.6). 7 Accordingly, assuming a 3.3% incidence of our primary outcome and considering a maximum recurrent VTE failure rate of 6.5% as the upper limit of a safe test, we determined that a sample of 246 patients who had a MRDTI negative for DVT and who completed follow-up would provide 80% power to reject the null hypothesis that the incidence of recurrent symptomatic VTE would be greater than 6.5%, at an overall one-sided significance level of 0.05. Assuming a 15% prevalence of DVT at baseline and anticipating a 5% incidence of loss to follow-up, we aimed to include