Patients with severe infection have an increased risk of cardiovascular events. A possible underlying mechanism is inflammation-induced platelet aggregation. We investigated whether... Show morePatients with severe infection have an increased risk of cardiovascular events. A possible underlying mechanism is inflammation-induced platelet aggregation. We investigated whether hyperaggregation occurs during infection, and whether aspirin inhibits this. In this multicentre, open-label, randomised controlled trial, patients hospitalised due to acute infection were randomised to receive 10 days of aspirin treatment (80 mg 1dd or 40 mg 2dd) or no intervention (1:1:1 allocation). Measurements were performed during infection (T1; days 1-3), after intervention (T2; day 14) and without infection (T3; day > 90). The primary endpoint was platelet aggregation measured by the Platelet Function Analyzer (R) closure time (CT), and the secondary outcomes were serum and plasma thromboxane B2 (sTxB2 and pTxB2). Fifty-four patients (28 females) were included between January 2018 and December 2020. CT was 18% (95%CI 6;32) higher at T3 compared with T1 in the control group (n = 16), whereas sTxB2 and pTxB2 did not differ. Aspirin prolonged CT with 100% (95%CI 77; 127) from T1 to T2 in the intervention group (n = 38), while it increased with only 12% (95%CI 1;25) in controls. sTxB2 decreased with 95% (95%CI - 97; - 92) from T1 to T2, while it increased in the control group. pTxB2 was not affected compared with controls. Platelet aggregation is increased during severe infection, and this can be inhibited by aspirin. Optimisation of the treatment regimen may further diminish the persisting pTxB2 levels that point towards remaining platelet activity. This trial was registered on 13 April 2017 at EudraCT (2016-004303-32). Show less
Background: Despite evidence of a quite large beneficial effect of endovascular treatment (EVT) for ischemic stroke caused by anterior circulation large vessel occlusion, many patients do not... Show moreBackground: Despite evidence of a quite large beneficial effect of endovascular treatment (EVT) for ischemic stroke caused by anterior circulation large vessel occlusion, many patients do not recover even after complete recanalization. To some extent, this may be attributable to incomplete microvascular reperfusion, which can possibly be improved by antiplatelet agents and heparin. It is unknown whether periprocedural antithrombotic medication in patients treated with EVT improves functional outcome. The aim of this study is to assess the effect of acetylsalicylic acid (ASA) and unfractionated heparin (UFH), alone, or in combination, given to patients with an ischemic stroke caused by an intracranial large vessel occlusion in the anterior circulation during EVT.Methods: MR CLEAN-MED is a multicenter phase III trial with a prospective, 2 x 3 factorial randomized, open label, blinded end-point (PROBE) design, which aims to enroll 1500 patients. The trial is designed to evaluate the effect of intravenous ASA (300 mg), UFH (low or moderate dose), both or neither as adjunctive therapy to EVT. We enroll adult patients with a clinical diagnosis of stroke (NIHSS >= 2) and with a confirmed intracranial large vessel occlusion in the anterior circulation on CTA or MRA, when EVT within 6 h from symptom onset is indicated and possible. The primary outcome is the score on the modified Rankin Scale (mRS) at 90 days. Treatment effect on the mRS will be estimated with ordinal logistic regression analysis, with adjustment for main prognostic variables. Secondary outcomes include stroke severity measured with the NIHSS at 24 h and at 5-7 days, follow-up infarct volume, symptomatic intracranial hemorrhage (sICH), and mortality.Discussion: Clinical equipoise exists whether antithrombotic medication should be administered during EVT for a large vessel occlusion, as ASA and/or UFH may improve functional outcome, but might also lead to an increased risk of sICH. When one or both of the study treatments show the anticipated effect on outcome, we will be able to improve outcome of patients treated with EVT by 5%. This amounts to more than 50 patients annually in the Netherlands, more than 1800 in Europe, and more than 1300 in the USA. Show less