TY - JOUR
T1 - Safety and efficacy of NA-1 in patients with iatrogenic stroke after endovascular aneurysm repair (ENACT)
T2 - A phase 2, randomised, double-blind, placebo-controlled trial
AU - Hill, Michael D.
AU - Martin, Renee H.
AU - Mikulis, David
AU - Wong, John H.
AU - Silver, Frank L.
AU - terBrugge, Karel G.
AU - Milot, Geneviève
AU - Clark, Wayne M.
AU - MacDonald, R. Loch
AU - Kelly, Michael E.
AU - Boulton, Melford
AU - Fleetwood, Ian
AU - McDougall, Cameron
AU - Gunnarsson, Thorsteinn
AU - Chow, Michael
AU - Lum, Cheemun
AU - Dodd, Robert
AU - Poublanc, Julien
AU - Krings, Timo
AU - Demchuk, Andrew M.
AU - Goyal, Mayank
AU - Anderson, Roberta
AU - Bishop, Julie
AU - Garman, David
AU - Tymianski, Michael
N1 - Funding Information:
MDH is funded by the Heart and Stroke Foundation of Alberta, Northwest Territory, and Nunavut and Alberta Innovates Health Solutions. RHM was contracted by NoNO Inc as a paid independent statistician to the trial. DM and MG are minor shareholders in the NonO Inc. DG is the Chief Operating Officer of NoNO and a shareholder in the company. JB and RA are employed by NoNO Inc and have options to purchase stock in the company. MT is the Chief Executive Officer of NoNO and a shareholder in the company. KGtB, GM, MB, MEK, TK, MC, TG, AMD, RD, FLS, WMC, RLM, IF, CM, CL, and JP declare that they have no conflicts of interest.
PY - 2012/11
Y1 - 2012/11
N2 - Background: Neuroprotection with NA-1 (Tat-NR2B9c), an inhibitor of postsynaptic density-95 protein, has been shown in a primate model of stroke. We assessed whether NA-1 could reduce ischaemic brain damage in human beings. Methods: For this double-blind, randomised, controlled study, we enrolled patients aged 18 years or older who had a ruptured or unruptured intracranial aneurysm amenable to endovascular repair from 14 hospitals in Canada and the USA. We used a computer-generated randomisation sequence to allocate patients to receive an intravenous infusion of either NA-1 or saline control at the end of their endovascular procedure (1:1; stratified by site, age, and aneurysm status). Both patients and investigators were masked to treatment allocation. The primary outcome was safety and primary clinical outcomes were the number and volume of new ischaemic strokes defined by MRI at 12-95 h after infusion. We used a modified intention-to-treat (mITT) analysis. This trial is registered with ClinicalTrials.gov, number NCT00728182. Findings: Between Sept 16, 2008, and March 30, 2011, we randomly allocated 197 patients to treatment-12 individuals did not receive treatment because they were found to be ineligible after randomisation, so the mITT population consisted of 185 individuals, 92 in the NA-1 group and 93 in the placebo group. Two minor adverse events were adjudged to be associated with NA-1; no serious adverse events were attributable to NA-1. We recorded no difference between groups in the volume of lesions by either diffusion-weighted MRI (adjusted p value=0·120) or fluid-attenuated inversion recovery MRI (adjusted p value=0·236). Patients in the NA-1 group sustained fewer ischaemic infarcts than did patients in the placebo group, as gauged by diffusion-weighted MRI (adjusted incidence rate ratio 0·53, 95% CI 0·38-0·74) and fluid-attenuated inversion recovery MRI (0·59, 0·42-0·83). Interpretation: Our findings suggest that neuroprotection in human ischaemic stroke is possible and that it should be investigated in larger trials. Funding: NoNO Inc and Arbor Vita Corp.
AB - Background: Neuroprotection with NA-1 (Tat-NR2B9c), an inhibitor of postsynaptic density-95 protein, has been shown in a primate model of stroke. We assessed whether NA-1 could reduce ischaemic brain damage in human beings. Methods: For this double-blind, randomised, controlled study, we enrolled patients aged 18 years or older who had a ruptured or unruptured intracranial aneurysm amenable to endovascular repair from 14 hospitals in Canada and the USA. We used a computer-generated randomisation sequence to allocate patients to receive an intravenous infusion of either NA-1 or saline control at the end of their endovascular procedure (1:1; stratified by site, age, and aneurysm status). Both patients and investigators were masked to treatment allocation. The primary outcome was safety and primary clinical outcomes were the number and volume of new ischaemic strokes defined by MRI at 12-95 h after infusion. We used a modified intention-to-treat (mITT) analysis. This trial is registered with ClinicalTrials.gov, number NCT00728182. Findings: Between Sept 16, 2008, and March 30, 2011, we randomly allocated 197 patients to treatment-12 individuals did not receive treatment because they were found to be ineligible after randomisation, so the mITT population consisted of 185 individuals, 92 in the NA-1 group and 93 in the placebo group. Two minor adverse events were adjudged to be associated with NA-1; no serious adverse events were attributable to NA-1. We recorded no difference between groups in the volume of lesions by either diffusion-weighted MRI (adjusted p value=0·120) or fluid-attenuated inversion recovery MRI (adjusted p value=0·236). Patients in the NA-1 group sustained fewer ischaemic infarcts than did patients in the placebo group, as gauged by diffusion-weighted MRI (adjusted incidence rate ratio 0·53, 95% CI 0·38-0·74) and fluid-attenuated inversion recovery MRI (0·59, 0·42-0·83). Interpretation: Our findings suggest that neuroprotection in human ischaemic stroke is possible and that it should be investigated in larger trials. Funding: NoNO Inc and Arbor Vita Corp.
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U2 - 10.1016/S1474-4422(12)70225-9
DO - 10.1016/S1474-4422(12)70225-9
M3 - Article
C2 - 23051991
AN - SCOPUS:84867641191
SN - 1474-4422
VL - 11
SP - 942
EP - 950
JO - The Lancet Neurology
JF - The Lancet Neurology
IS - 11
ER -