TY - JOUR
T1 - Rationale and methods of the Antioxidant and NMDA receptor blocker Weans Anoxic brain damage of KorEa OHCA patients (AWAKE) trial
AU - Choi, Jin Ho
AU - Chun, Byeong Jo
AU - Yeom, Seok Ran
AU - Chung, Sung Phil
AU - Lee, Young Hwan
AU - Kim, Yun Hee
AU - Lee, Ji Sung
AU - Lee, Jin Hwan
AU - Lee, Hwan Goo
AU - Jin, Jing Yu
AU - An, Chun San
AU - Gwag, Byoung Joo
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Background: Ischemic brain injury is a major hurdle that limits the survival of resuscitated out-of-hospital cardiac arrest (OHCA). Methods: The aim of this study is to assess the feasibility and potential for reduction of ischemic brain injury in adult OHCA patients treated with high- or low-dose Neu2000K, a selective blocker of N-methyl-d-aspartate (NMDA) type 2B receptor and also a free radical scavenger, or given placebo. This study is a phase II, multicenter, randomized, double-blinded, prospective, intention-to-treat, placebo-controlled, three-armed, safety and efficacy clinical trial. This trial is a sponsor-initiated trial supported by GNT Pharma. Successfully resuscitated OHCA patients aged 19 to 80 years would be included. The primary outcome is blood neuron-specific enolase (NSE) level on the 3rd day. The secondary outcomes are safety, efficacy defined by study drug administration within 4 h in > 90% of participants, daily NSE up to 5th day, blood S100beta, brain MRI apparent diffusion coefficient imaging, cerebral performance category (CPC), and Modified Rankin Scale (mRS) at 5th, 14th, and 90th days. Assuming NSE of 42 ± 80 and 80 ± 80 μg/L in the treatment (high- and low-dose Neu2000K) and control arms with 80% power, a type 1 error rate of 5%, and a 28% of withdrawal prior to the endpoint, the required sample size is 150 patients. Discussion: The AWAKE trial explores a new multi-target neuroprotectant for the treatment of resuscitated OHCA patients. Trial registration: ClinicalTrials.gov NCT03651557. Registered on August 29, 2018.
AB - Background: Ischemic brain injury is a major hurdle that limits the survival of resuscitated out-of-hospital cardiac arrest (OHCA). Methods: The aim of this study is to assess the feasibility and potential for reduction of ischemic brain injury in adult OHCA patients treated with high- or low-dose Neu2000K, a selective blocker of N-methyl-d-aspartate (NMDA) type 2B receptor and also a free radical scavenger, or given placebo. This study is a phase II, multicenter, randomized, double-blinded, prospective, intention-to-treat, placebo-controlled, three-armed, safety and efficacy clinical trial. This trial is a sponsor-initiated trial supported by GNT Pharma. Successfully resuscitated OHCA patients aged 19 to 80 years would be included. The primary outcome is blood neuron-specific enolase (NSE) level on the 3rd day. The secondary outcomes are safety, efficacy defined by study drug administration within 4 h in > 90% of participants, daily NSE up to 5th day, blood S100beta, brain MRI apparent diffusion coefficient imaging, cerebral performance category (CPC), and Modified Rankin Scale (mRS) at 5th, 14th, and 90th days. Assuming NSE of 42 ± 80 and 80 ± 80 μg/L in the treatment (high- and low-dose Neu2000K) and control arms with 80% power, a type 1 error rate of 5%, and a 28% of withdrawal prior to the endpoint, the required sample size is 150 patients. Discussion: The AWAKE trial explores a new multi-target neuroprotectant for the treatment of resuscitated OHCA patients. Trial registration: ClinicalTrials.gov NCT03651557. Registered on August 29, 2018.
KW - Free radical scavenger
KW - Ischemic-reperfusion brain injury
KW - Neu2000K
KW - NMDA antagonist
KW - Out-of-hospital cardiac arrest
KW - Randomized controlled trial
UR - https://www.scopus.com/pages/publications/85135037266
U2 - 10.1186/s13063-022-06452-0
DO - 10.1186/s13063-022-06452-0
M3 - Article
C2 - 35871083
AN - SCOPUS:85135037266
SN - 1745-6215
VL - 23
JO - Trials
JF - Trials
IS - 1
M1 - 587
ER -
