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Antioxidant and NMDA Receptor Blocker Wins Anoxic Brain Damage of KorEa OHCA Patients (AWAKE)

Primary Purpose

Cardiac Arrest

Status
Unknown status
Phase
Phase 2
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Neu2000KWL High-dose group
Neu2000KWL Low-dose group
Placebo
Sponsored by
GNT Pharma
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cardiac Arrest focused on measuring Neu2000KWL, cerebral performance category, out-of-hospital cardiac arrest, neuroprotection, glutamate, N-Methyl-D-aspartate (NMDA) receptor antagonist, Anti-oxidant, free radical

Eligibility Criteria

19 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Kyungpook National University Hospital
  • Soonchunhyang University Bucheon Hospital
  • Pusan National University Hospital
  • Chonnam National University Hospital
  • Gangnam Severance Hospital
  • Samsung Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

Neu2000KWL high dose

Neu2000KWL low dose

saline

Arm Description

Outcomes

Primary Outcome Measures

Verification of difference between of Neuron specific enolase (NSE) value at after 4th infusion of Neu2000KWL.
Blood concentration of neuron specific enolase (NSE)

Secondary Outcome Measures

Verification of difference between the cumulative of neuron specific enolase (NSE) values at after 6th infusion of Neu2000KWL
Cumulative Blood concentration of neuron specific enolase (NSE)
Verification of the difference between groups of Change in NSE values at after the 2nd infusion of Neu2000KWL and after the 6th infusion
The difference of blood neuron specific enolase (NSE) between 24 hour (day 1) and 72 hour (day 3) after the first infusion of Neu2000KWL.
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
The difference of blood neuron specific enolase (NSE) between day 4 and day 5
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
Blood neuron specific enolase (NSE) at day 5
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.
Neurological function evaluated by cerebral performance category (CPC), which ranges 1 to 5 (1: best, 5: worst), and neurological function evaluated by modified Rankin Scale (mRS), which ranges 0 to 6 (0:best, 6: worst)
Verification of difference between groups of Cumulative value of blood S100beta from 6th infusion after 1st infusion of Neu2000KWL.
Cumulative blood concentration of S100beta .

Full Information

First Posted
July 26, 2018
Last Updated
March 5, 2019
Sponsor
GNT Pharma
Collaborators
Samsung Medical Center, Chonnam National University Hospital, Gangnam Severance Hospital, Kyungpook National University Hospital, Pusan National University Hospital, Soonchunhyang University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT03651557
Brief Title
Antioxidant and NMDA Receptor Blocker Wins Anoxic Brain Damage of KorEa OHCA Patients
Acronym
AWAKE
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

2. Study Status

Record Verification Date
August 2018
Overall Recruitment Status
Unknown status
Study Start Date
November 29, 2018 (Actual)
Primary Completion Date
May 2021 (Anticipated)
Study Completion Date
May 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GNT Pharma
Collaborators
Samsung Medical Center, Chonnam National University Hospital, Gangnam Severance Hospital, Kyungpook National University Hospital, Pusan National University Hospital, Soonchunhyang University Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Masking Description
Double Blind (Subject, Caregiver, Investigator)
Allocation
Randomized
Enrollment
150 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Neu2000KWL high dose
Arm Type
Experimental
Arm Title
Neu2000KWL low dose
Arm Type
Experimental
Arm Title
saline
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Neu2000KWL High-dose group
Intervention Description
1st infusion of 1500mg in patients within 4 hours following sudden cardiac arrest onset followed by 5 consecutive infusions of 750 mg at intervals of 12 hours(Total drug dosage is 5250mg.)
Intervention Type
Drug
Intervention Name(s)
Neu2000KWL Low-dose group
Intervention Description
1st infusion of 750mg in patients within 4 hours following sudden cardiac arrest onset followed by 5 consecutive infusions of 500 mg at intervals of 12 hours (Total drug dosage is 3250mg.)
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
1st infusion of the same volume of saline in patients within 4 hours following sudden cardiac arrest onset followed by 5 consecutive infusions of the same volume of saline at intervals of 12 hours
Primary Outcome Measure Information:
Title
Verification of difference between of Neuron specific enolase (NSE) value at after 4th infusion of Neu2000KWL.
Description
Blood concentration of neuron specific enolase (NSE)
Time Frame
The 3rd day of study (which corresponds to finished 4th infusion of Neu2000KWL).
Secondary Outcome Measure Information:
Title
Verification of difference between the cumulative of neuron specific enolase (NSE) values at after 6th infusion of Neu2000KWL
Description
Cumulative Blood concentration of neuron specific enolase (NSE)
Time Frame
The 4th day of study (which corresponds to finished 6th infusion of Neu2000KWL).
Title
Verification of the difference between groups of Change in NSE values at after the 2nd infusion of Neu2000KWL and after the 6th infusion
Description
The difference of blood neuron specific enolase (NSE) between 24 hour (day 1) and 72 hour (day 3) after the first infusion of Neu2000KWL.
Time Frame
At the 24 hours and 72 hours after the first infusion of Neu2000KWL.
Title
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
Description
The difference of blood neuron specific enolase (NSE) between day 4 and day 5
Time Frame
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).
Title
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
Description
Blood neuron specific enolase (NSE) at day 5
Time Frame
The 5th day of study (which corresponds to 48 hours after finished treatment using Neu2000KWL).
Title
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.
Description
Neurological function evaluated by cerebral performance category (CPC), which ranges 1 to 5 (1: best, 5: worst), and neurological function evaluated by modified Rankin Scale (mRS), which ranges 0 to 6 (0:best, 6: worst)
Time Frame
5 day, 14 day, or discharge within 14 days, and 90 days after 1st infusion of Neu2000KWL
Title
Verification of difference between groups of Cumulative value of blood S100beta from 6th infusion after 1st infusion of Neu2000KWL.
Description
Cumulative blood concentration of S100beta .
Time Frame
The 4th day of study (which corresponds to finished 6th infusion of Neu2000KWL).
Other Pre-specified Outcome Measures:
Title
Serious adverse event
Description
Safety Outcome Measure Number of participants with treatment-related adverse events assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
Time Frame
90 days
Title
Mortality within 90 days
Description
Safety Outcome Measure
Time Frame
90 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
19 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 19 Years to 80 Years (Adult) Out-of-hospital cardiac arrest caused by non-perfusing cardiac rhythm Successful resuscitation accompanied by ROSC time of more than 20 min Therapeutic hypothermia is planned or initiated The first infusion is planned within 4 hours after ROSC Informed consent is obtained from patient or family member(s) No concern with previous cardiovascular surgery Exclusion Criteria: Hypersensitivity to aspirin or sulfasalazine Unwitnessed cardiac arrest CPR time > 60 min Therapeutic hypothermia is not planned Use of extracorporeal membrane oxygenation (ECMO) at initiation of in-hospital resuscitation (E-CPR) 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 Pregnant or lactating women Participated in other clinical studies within 90 days before randomization; or participating in other clinical trials at present Intracranial bleeding verified by first brain CT imaging The investigators consider the patients are not suitable for this trial
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jin-Ho Choi, MD
Organizational Affiliation
Professor, Department of Emergency Medicine, Samsung Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Kyungpook National University Hospital
City
Daegu
State/Province
Korea
ZIP/Postal Code
41944
Country
Korea, Republic of
Facility Name
Soonchunhyang University Bucheon Hospital
City
Bucheon
ZIP/Postal Code
14584
Country
Korea, Republic of
Facility Name
Pusan National University Hospital
City
Busan
ZIP/Postal Code
49241
Country
Korea, Republic of
Facility Name
Chonnam National University Hospital
City
Gwangju
ZIP/Postal Code
61469
Country
Korea, Republic of
Facility Name
Gangnam Severance Hospital
City
Seoul
ZIP/Postal Code
06273
Country
Korea, Republic of
Facility Name
Samsung Medical Center
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
35871083
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.
Results Reference
derived

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Antioxidant and NMDA Receptor Blocker Wins Anoxic Brain Damage of KorEa OHCA Patients

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