MOdified DIagnostic strateGy to safely ruLe-out pulmonary embolism In the emergency depArtment: study protocol for the Non-Inferiority MODIGLIANI cluster cross-over randomized trial

Abstract

Introduction: In the work-up strategy for pulmonary embolism (PE) in the ED, the recently introduced YEARS rule allows the raising of the D-dimer threshold to 1000 ng/ml in patients with no signs of deep venous thrombosis and no hemoptysis and in whom PE is not the most likely diagnosis. However, this decision rule has never been prospectively compared to the usual strategy. Furthermore, it is unclear if the YEARS rule can be used on top of the Pulmonary Embolism Rule-out Criteria (PERC). We aim to assess the non-inferiority of YEARS compared to current guidelines to rule out PE among PERC-positive ED patients with suspicion of PE. Methods/design: The MODIGLIANI study is a multicenter, European, non-inferiority, cluster-randomized, two periods cross-over, controlled trial. Each center will be randomized for the sequence of two 4-month periods: intervention (MOdified Diagnostic Strategy: MODS) followed by control (usual care), or control followed by intervention with 1 month of "wash-out" between the two periods. In the control period, the threshold will be as usual (500 ng/ml for patients aged 50 years or younger and age × 10 for older patients). In the MODS period, the threshold of D-dimers to rule out PE will be raised to 1000 ng/ml if no item of the YEARS score is present or will remain unchanged otherwise. Patients will be included if they have a suspicion of PE, defined as chest pain, dyspnea, or syncope. Non-inclusion criteria comprise a high clinical probability of PE or PERC-negative patients with low clinical probability. Ethics and dissemination: The study has received the following approvals:

Effect of a Diagnostic Strategy Using an Elevated and Age-Adjusted D-Dimer Threshold on Thromboembolic Events in Emergency Department Patients With Suspected Pulmonary Embolism

“…The design of this cluster-randomized, crossover, noninferiority trial has been published previously, and the protocol and statistical analysis plan are available in Supplement 1 and Supplement 2, respectively. The trial was funded by the French Ministry of Health and sponsored by the Assistance Publique–Hôpitaux de Paris [APHP]; Paris, France).…”

Cost-effectiveness of modified diagnostic strategy to safely rule-out pulmonary embolism in the emergency department: a non-inferiority cluster crossover randomized trial (MODIGLIA-NI)

“…We followed a detailed health economics analysis plan developed before the end of the trial and last modified before the freezing of the trial database. We chose a cost-effectiveness analysis instead of a cost minimization procedure, with a non-inferiority margin of 1.35%, as described in the published study protocol [ 9 ]. This economic evaluation of the innovative diagnostic strategy of PE followed the recommendations from the French national health authority and the reporting follows the CHEERS statement for single trial-based studies [ 10 ].…”

Cost-effectiveness of MOdified DIagnostic strateGy to safely ruLe-out pulmonary embolism in the emergency depArtment: A Non-Inferiority cluster crossover randomized trial (MODIGLIA- NI)

“…We followed a detailed health economics analysis plan developed before the end of the trial and last modi ed before the freezing of the trial database. We chose a cost-effectiveness analysis instead of a cost minimization procedure, with a non-inferiority margin of 1.35%, as described in the published study protocol (9). This economic evaluation of the innovative diagnostic strategy of PE followed the recommendations from the French national health authority and the reporting follows the CHEERS statement for single trial-based studies (10).…”