TY - JOUR
T1 - Multicenter randomized clinical trial of endovascular treatment for acute ischemic stroke. The effect of periprocedural medication
T2 - acetylsalicylic acid, unfractionated heparin, both, or neither (MR CLEAN-MED). Rationale and study design
AU - Chalos, Vicky
AU - A van de Graaf, Rob
AU - Roozenbeek, Bob
AU - C G M van Es, Adriaan
AU - M den Hertog, Heleen
AU - Staals, Julie
AU - van Dijk, Lukas
AU - F M Jenniskens, Sjoerd
AU - J van Oostenbrugge, Robert
AU - H van Zwam, Wim
AU - B W E M Roos, Yvo
AU - B L M Majoie, Charles
AU - F Lingsma, Hester
AU - van der Lugt, Aad
AU - W J Dippel, Diederik
AU - MR CLEAN-MED investigators
AU - Bokkers, R.P.
AU - van der Hoorn, Anouk
PY - 2020
Y1 - 2020
N2 - 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 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 × 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.TRIAL REGISTRATION: ISRCT, ISRCTN76741621 . Dec 6, 2017.
AB - 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 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 × 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.TRIAL REGISTRATION: ISRCT, ISRCTN76741621 . Dec 6, 2017.
KW - Adult
KW - Aspirin/therapeutic use
KW - Brain Ischemia/drug therapy
KW - Endovascular Procedures
KW - Heparin/therapeutic use
KW - Humans
KW - Ischemic Stroke/drug therapy
KW - Multicenter Studies as Topic
KW - Prospective Studies
KW - Randomized Controlled Trials as Topic
KW - Thrombectomy
KW - Treatment Outcome
U2 - 10.1186/s13063-020-04514-9
DO - 10.1186/s13063-020-04514-9
M3 - Article
C2 - 32665035
SN - 1745-6215
VL - 21
JO - Trials
JF - Trials
IS - 1
M1 - 644
ER -