The TIMING-study will use the Swedish Stroke Register (Riksstroke) for enrolment, randomization and follow-up; a method called R-RCT. The intervention is the timing of treatment onset. Eligible patients will be randomized within 72 hours (1:1 i.e. equal in the study arms) from stroke onset by the treating physician at the patient’s local hospital. The choice of NOAC (i.e. apixaban, dabigatran, edoxaban or rivaroxaban) after the acute ischemic stroke is at the discretion of the treating physician. If eligible and willing to participate, the patient will be randomly allocated to early (≤4 days) or delayed (≥5-10 days) start of NOAC by a central computer within the Swedish Stroke Register/TIMING infrastructure. The study protocol is published as an open access article in Trials.
Primary outcome, composite
Recurrent ischemic stroke within 90 days, defined as a new focal neurological deficit of sudden onset lasting at least 24 h (or <24 h if following therapeutic intervention, i.e. thrombolysis or thrombectomy, or if the deficit results in death < 24 h), occurring >24 hours after the index ischemic stroke, irrespective of vascular territory and that is not attributable to edema, brain shift, hemorrhagic transformation, intercurrent illness, hypoxia, or drug toxicity.
Symptomatic ICH within 90 days, defined as a new focal neurological deficit of sudden onset lasting at least 24 h with documented ICH on imaging. Any intraparenchymal hematoma (≥10mm) will be considered, including hemorrhagic transformation of the index ischemic stroke. However microhemorrhages (<10mm) are not considered to be an ICH. ICH will be classified as symptomatic if it is associated with ≥4 points in total NIHSS or ≥2 points in one NIHSS category.
Death considered as all-cause mortality within 90 days.
Recruitment of patients ended in December 2020. The 34 participating Stroke Units (out of 72) in Sweden, recruited approximately 900 patients in TIMING. Result are expected in September 2020.
Read more on www.ClinicalTrials.gov or download (open access) the published study protocol from Trials.