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

• Sponsor: GNT Pharma (Industry)
• Overall Status: Unknown status
• CT.gov ID: NCT03651557
• Collaborator: Samsung Medical Center (Other), Chonnam National University Hospital (Other), Gangnam Severance Hospital (Other), Kyungpook National University Hospital (Other), Pusan National University Hospital (Other), Soonchunhyang University Hospital (Other)
• Enrollment: 150
• Locations: 6
• Arms: 3
• Anticipated Duration (Months): 29
• Patients Per Site: 25
• Patients Per Site Per Month: 0.9

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Cardiac Arrest	Drug: Neu2000KWL High-dose group; Drug: Neu2000KWL Low-dose group; Drug: Placebo	Phase 2

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.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 150 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Masking Description: Double Blind (Subject, Caregiver, Investigator)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Nov 29, 2018
• Anticipated Primary Completion Date: May 1, 2021
• Anticipated Study Completion Date: May 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Neu2000KWL high dose	Drug: Neu2000KWL High-dose group; 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.)
Experimental: Neu2000KWL low dose	Drug: Neu2000KWL Low-dose group; 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.)
Placebo Comparator: saline	Drug: Placebo; 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

Outcome Measures

Primary Outcome Measures

1. Verification of difference between of Neuron specific enolase (NSE) value at after 4th infusion of Neu2000KWL. [The 3rd day of study (which corresponds to finished 4th infusion of Neu2000KWL).]

   Blood concentration of neuron specific enolase (NSE)

Secondary Outcome Measures

1. Verification of difference between the cumulative of neuron specific enolase (NSE) values at after 6th infusion of Neu2000KWL [The 4th day of study (which corresponds to finished 6th infusion of Neu2000KWL).]

   Cumulative Blood concentration of neuron specific enolase (NSE)

2. Verification of the difference between groups of Change in NSE values at after the 2nd infusion of Neu2000KWL and after the 6th infusion [At the 24 hours and 72 hours after the first infusion of Neu2000KWL.]

   The difference of blood neuron specific enolase (NSE) between 24 hour (day 1) and 72 hour (day 3) after the first infusion of Neu2000KWL.

3. 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 4th and 5th day of study (which corresponds to the timepoint of finished treatment using Neu2000KWL and 24 hour after finished treatment using Neu2000KWL).]

   The difference of blood neuron specific enolase (NSE) between day 4 and day 5

4. 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 [The 5th day of study (which corresponds to 48 hours after finished treatment using Neu2000KWL).]

   Blood neuron specific enolase (NSE) at day 5

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. [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)

6. Verification of difference between groups of Cumulative value of blood S100beta from 6th infusion after 1st infusion of Neu2000KWL. [The 4th day of study (which corresponds to finished 6th infusion of Neu2000KWL).]

   Cumulative blood concentration of S100beta .

Other Outcome Measures

1. Serious adverse event [90 days]

   Safety Outcome Measure Number of participants with treatment-related adverse events assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0

2. Mortality within 90 days [90 days]

   Safety Outcome Measure

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kyungpook National University Hospital	Daegu	Korea	Korea, Republic of	41944
2	Soonchunhyang University Bucheon Hospital	Bucheon		Korea, Republic of	14584
3	Pusan National University Hospital	Busan		Korea, Republic of	49241
4	Chonnam National University Hospital	Gwangju		Korea, Republic of	61469
5	Gangnam Severance Hospital	Seoul		Korea, Republic of	06273
6	Samsung Medical Center	Seoul		Korea, Republic of	06351

Sponsors and Collaborators

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

Investigators

• Principal Investigator: Jin-Ho Choi, MD, Professor, Department of Emergency Medicine, Samsung Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: GNT Pharma
• ClinicalTrials.gov Identifier: NCT03651557
• Other Study ID Numbers: Neu2000KWL-P02
• First Posted: Aug 29, 2018
• Last Update Posted: Mar 6, 2019
• Last Verified: Aug 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by GNT Pharma: Neu2000KWL; cerebral performance category; out-of-hospital cardiac arrest; neuroprotection; glutamate; N-Methyl-D-aspartate (NMDA) receptor antagonist; Anti-oxidant; free radical
• Additional relevant MeSH terms: Heart Arrest; Out-of-Hospital Cardiac Arrest; Salicylates

Study Results

No Results Posted as of Mar 6, 2019