Fig. 5

Flow of patients in the acute stroke trials of the Collaboration for New Treatments of Acute Stroke (CONTRAST) consortium. Abbreviations: MR ASAP, Multicentre Randomised trial of Acute Stroke treatment in the Ambulance with a nitroglycerin Patch; ED, emergency department; DIST pilot study, Dutch Intracerebral Hemorrhage Surgery Trial - pilot study; minimally-invasive endoscopy-guided surgery for spontaneous intracerebral hemorrhage; LVO, large vessel occlusion; IVT, intravenous thrombolysis with alteplase; MR CLEAN-MED, multicenter randomized clinical trial of endovascular treatment for acute ischemic stroke. The effect of periprocedural medication: acetylsalicylic acid, unfractionated heparin, both or neither; MR CLEAN-NO IV, intravenous treatment followed by endovascular treatment versus direct endovascular treatment for acute ischemic stroke caused by a proximal intracranial occlusion; MR CLEAN-LATE: Multicenter Randomized Clinical Trial of Endovascular Stroke treatment in The Netherlands for Late arrivals. Captions: *Considerations: The CONTRAST trials are independent clinical trials. Patients included in MR ASAP may also be included in one of the other trials. We will perform pre-specified subgroup analyses to test for interaction between the different study treatments. At the first ED (i.e., primary stroke center or participating EVT center), all patients with a probable diagnosis of acute stroke will undergo non-invasive imaging to differentiate between cerebral infarction or intracranial hemorrhage and to assess an intracranial LVO in the anterior circulation. When the first ED is a primary stroke center and the patient could be eligible for DIST pilot study, MR CLEAN-MED, or MR CLEAN-LATE, the patient should be transferred to a participating EVT center. Patients arriving at a primary stroke center first will generally not be eligible for MR CLEAN-NO IV, since IVT cannot be withheld until after patient transfer to the EVT center, unless the perceived contraindications for IVT are not present anymore upon arrival at the EVT center. Then, inclusion in MR CLEAN-NO IV will have priority over inclusion in other trials. Competition between the three MR CLEAN trials will not occur