Clinical trial NCT03651557: Antioxidant and NMDA Receptor Blocker Wins Anoxic Brain Damage of KorEa OHCA Patients
Official title: A Phase II, Double-blind, Randomized, Placebo-controlled, Multicenter Trial to Assess the Efficacy and Safety of Neu2000KWL in Patients Who Resuscitated After Out-of-hospital Cardiac Arrest Patient and Receiving Therapeutic Hypothermia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Cardiac Arrest
Keywords: Neu2000KWL
cerebral performance category
out-of-hospital cardiac arrest
neuroprotection
glutamate
N-Methyl-D-aspartate (NMDA) receptor antagonist
Anti-oxidant
free radical
Lead sponsor: GNT Pharma
Sponsor class: INDUSTRY
Collaborators: name: Samsung Medical Center
name: Chonnam National University Hospital
name: Gangnam Severance Hospital
name: Kyungpook National University Hospital
name: Pusan National University Hospital
name: Soonchunhyang University Hospital
First posted: 2018-08-29
Enrollment: 150
Sex: ALL
Minimum age (years): 19
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study aims to investigate the efficacy and safety of Neu2000KWL, a neuroprotectant, in patients resuscitated from out-of-hospital cardiac arrest and receiving therapeutic hypothermia.

Detailed description: Lack of good neurological recovery is the biggest hurdle in the treatment of out-of-hospital cardia arrest. Neu2000KWL, a N-Methyl-D-aspartate (NMDA) receptor antagonist and an antioxidant, attenuated cerebral neuronal death and reduced hypoxic injury of brain in preclinical studies. Phase I clinical study has revealed that Neu2000KWL is very safe for treating human. In current study, the investigators will assess the efficacy of Neu2000KWL to compare the neurological biomarker, brain imaging, and clinical outcomes of patients successfully resuscitated from out-of-cardiac arrest treated by 3-day infusion of Neu2000KWL with patients assigned to placebo arm.

Eligibility criteria: Inclusion Criteria:

1. 19 Years to 80 Years (Adult)
2. Out-of-hospital cardiac arrest caused by non-perfusing cardiac rhythm
3. Successful resuscitation accompanied by ROSC time of more than 20 min
4. Therapeutic hypothermia is planned or initiated
5. The first infusion is planned within 4 hours after ROSC
6. Informed consent is obtained from patient or family member(s)
7. No concern with previous cardiovascular surgery

Exclusion Criteria:

1. Hypersensitivity to aspirin or sulfasalazine
2. Unwitnessed cardiac arrest
3. CPR time \> 60 min
4. Therapeutic hypothermia is not planned
5. Use of extracorporeal membrane oxygenation (ECMO) at initiation of in-hospital resuscitation (E-CPR)
6. Very poor prognosis is expected: patients with (A) non-cardiac or respiratory arrest, (B) poor basal neurological status (C) secondary cardiac arrest caused by trauma, major bleeding, acute neurologic disease including stroke or tumor, (D) multiorgan failure or advanced malignancy
7. Pregnant or lactating women
8. Participated in other clinical studies within 90 days before randomization; or participating in other clinical trials at present
9. Intracranial bleeding verified by first brain CT imaging
10. The investigators consider the patients are not suitable for this trial

Primary outcomes:
measure: Verification of difference between of Neuron specific enolase (NSE) value at after 4th infusion of Neu2000KWL.
timeFrame: The 3rd day of study (which corresponds to finished 4th infusion of Neu2000KWL).
Secondary outcomes:
measure: Verification of difference between the cumulative of neuron specific enolase (NSE) values at after 6th infusion of Neu2000KWL
timeFrame: The 4th day of study (which corresponds to finished 6th infusion of Neu2000KWL).
measure: Verification of the difference between groups of Change in NSE values at after the 2nd infusion of Neu2000KWL and after the 6th infusion
timeFrame: At the 24 hours and 72 hours after the first infusion of Neu2000KWL.
measure: Verification of difference between each group of NSE values at after 6th infusion after 1st infusion of Neu2000KWL and 24 hours after end of last infusion
timeFrame: The 4th and 5th day of study (which corresponds to the timepoint of finished treatment using Neu2000KWL and 24 hour after finished treatment using Neu2000KWL).
measure: Verification of difference between the cerebral infarction at analysis of brain MRI's Apparent Diffusion Coefficient(ADC) images within 48 hours of the last infusion of Neu2000KWL
timeFrame: The 5th day of study (which corresponds to 48 hours after finished treatment using Neu2000KWL).
measure: Verification of difference between groups of Neurological function evaluated by cerebral performance category (CPC) and modified Rankin Scale (mRS) at 5 day, 14 day, or discharge within 14 days, and 90 days after 1st infusion of Neu2000KWL.
timeFrame: 5 day, 14 day, or discharge within 14 days, and 90 days after 1st infusion of Neu2000KWL
measure: Verification of difference between groups of Cumulative value of blood S100beta from 6th infusion after 1st infusion of Neu2000KWL.
timeFrame: The 4th day of study (which corresponds to finished 6th infusion of Neu2000KWL).
Other outcomes:
measure: Serious adverse event
timeFrame: 90 days
measure: Mortality within 90 days
timeFrame: 90 days
Locations:
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital
state: Korea
city: Bucheon
country: Korea, Republic of
facility: Soonchunhyang University Bucheon Hospital
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
Study officials:
affiliation: Professor, Department of Emergency Medicine, Samsung Medical Center
name: Jin-Ho Choi, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Choi JH, Chun BJ, Yeom SR, Chung SP, Lee YH, Kim YH, Lee JS, Lee JH, Lee HG, Jin JY, An CS, Gwag BJ. Rationale and methods of the Antioxidant and NMDA receptor blocker Weans Anoxic brain damage of KorEa OHCA patients (AWAKE) trial. Trials. 2022 Jul 23;23(1):587. doi: 10.1186/s13063-022-06452-0.