Safety and Optimal Neuroprotection of neu2000 in acute Ischemic stroke with reCanalization: study protocol for a randomized, double-blinded, placebo-controlled, phase-II trial

Trials

on the behalf of the SONIC investigators¹  Ángel Chamorro²  Mun Hee Choi³  Ji Man Hong³  Dong-Ick Shin⁴  Seong Hwan Ahn⁵  Sung-Il Sohn⁶  Yeong-Bae Lee⁷  Yang-Ha Hwang⁸  Dennis W. Choi⁹ 

[1] ;Comprehensive Stroke Center, Department of Neuroscience, Hospital Clinic, University of Barcelona and August Pi I Sunyer Biomedical Research Institute (IDIBAPS);Department of Neurology, Ajou University School of Medicine, Ajou University Medical Center;Department of Neurology, Chungbuk National University Hospital, Chungbuk National University College of Medicine;Department of Neurology, College of Medicine, Chosun University;Department of Neurology, Dongsan Medical Center, Keimyung University;Department of Neurology, Gachon University Gil Medical Center;Department of Neurology, Kyungpook National University Hospital;Department of Neurology, Stony Brook University;

关键词: Endovascular recanalization;    Ischemia and reperfusion;    Neuroprotectants;    Collateral;   

DOI  :  10.1186/s13063-018-2746-9

来源: DOAJ

【 摘 要 】

Abstract Background The potential of neuroprotective agents should be revisited in the era of endovascular thrombectomy (EVT) for acute large-artery occlusion because their preclinical effects have been optimized for ischemia and reperfusion injury. Neu2000, a derivative of sulfasalazine, is a multi-target neuroprotectant. It selectively blocks N-methyl-D-aspartate receptors and scavenges for free radicals. This trial aimed to determine whether neuroprotectant administration before EVT is safe and leads to a more favorable outcome. Methods This trial is a phase-II, multicenter, three-arm, randomized, double-blinded, placebo-controlled, blinded-endpoint drug trial that enrolled participants aged ≥ 19 years undergoing an EVT attempt less than 8 h from symptom onset, with baseline National Institutes of Health Stroke Scale (NIHSS) score ≥ 8, Alberta Stroke Program Early CT score ≥ 6, evidence of large-artery occlusion, and at least moderate collaterals on computed tomography angiography. EVT-attempted patients are randomized into control, low-dose (2.75 g), and high-dose (5.25 g) Neu2000KWL over 5 days. Seventy participants per group are enrolled for 90% power, assuming that the treatment group has a 28.4% higher proportion of participants with functional independence than the placebo group. The primary outcome, based on intention-to-treat criteria is the improvement of modified Rankin Scale (mRS) scores at 3 months using a dichotomized model. Safety outcomes include symptomatic intracranial hemorrhage within 5 days. Secondary outcomes are distributional change of mRS, mean differences in NIHSS score, proportion of NIHSS score 0–2, and Barthel Index > 90 at 1 and 4 weeks, and 3 months. Discussion The trial results may provide information on new therapeutic options as multi-target neuroprotection might mitigate reperfusion injury in patients with acute ischemic stroke before EVT. Trial registration ClinicalTrials.gov, ID: NCT02831088. Registered on 13 July 2016.

【 授权许可】

Unknown