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. 2018 Jul 13;19(1):375. doi: 10.1186/s13063-018-2746-9.


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:, ID: NCT02831088 . Registered on 13 July 2016.

Keywords: Collateral; Endovascular recanalization; Ischemia and reperfusion; Neuroprotectants.

Publication types

  • Clinical Trial Protocol

MeSH terms

  • Brain Ischemia / diagnosis
  • Brain Ischemia / physiopathology
  • Brain Ischemia / therapy*
  • Clinical Trials, Phase II as Topic
  • Disability Evaluation
  • Double-Blind Method
  • Endovascular Procedures* / adverse effects
  • Fluorobenzenes / adverse effects
  • Fluorobenzenes / therapeutic use*
  • Humans
  • Multicenter Studies as Topic
  • Neuroprotective Agents / adverse effects
  • Neuroprotective Agents / therapeutic use*
  • Prospective Studies
  • Randomized Controlled Trials as Topic
  • Recovery of Function
  • Republic of Korea
  • Salicylates / adverse effects
  • Salicylates / therapeutic use*
  • Stroke / diagnosis
  • Stroke / physiopathology
  • Stroke / therapy*
  • Thrombectomy / adverse effects
  • Thrombectomy / methods*
  • Time Factors
  • Treatment Outcome
  • meta-Aminobenzoates / adverse effects
  • meta-Aminobenzoates / therapeutic use*


  • 2-hydroxy-5-(2,3,5,6-tetrafluoro-4-trifluoromethyl-benzylamino)benzoic acid
  • Fluorobenzenes
  • Neuroprotective Agents
  • Salicylates
  • meta-Aminobenzoates

Associated data