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

Cardiac Arrest Clinical Trial

— 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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT03651557
• Other study ID #: Neu2000KWL-P02
• Status: Enrolling by invitation
• Phase: Phase 2
• Start date: November 29, 2018
• Est. completion date: May 2021

Study information

• Verified date: August 2018
• Source: GNT Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 150
• Est. completion date: May 2021
• Est. primary completion date: May 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Cardiac Arrest
• Heart Arrest
• Out-of-Hospital Cardiac Arrest

Intervention

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.)
• 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
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

Locations

Country	Name	City	State
Korea, Republic of	Soonchunhyang University Bucheon Hospital	Bucheon
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	Kyungpook National University Hospital	Daegu	Korea
Korea, Republic of	Chonnam National University Hospital	Gwangju
Korea, Republic of	Gangnam Severance Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul

Sponsors (7)

Lead Sponsor	Collaborator
GNT Pharma	Chonnam National University Hospital, Gangnam Severance Hospital, Kyungpook National University, Pusan National University Hospital, Samsung Medical Center, Soonchunhyang University Hospital

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Serious adverse event	Safety Outcome Measure; Number of participants with treatment-related adverse events assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0	90 days
Other	Mortality within 90 days	Safety Outcome Measure	90 days
Primary	Verification of difference between of Neuron specific enolase (NSE) value at after 4th infusion of Neu2000KWL.	Blood concentration of neuron specific enolase (NSE)	The 3rd day of study (which corresponds to finished 4th infusion of Neu2000KWL).
Secondary	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)	The 4th day of study (which corresponds to finished 6th infusion of Neu2000KWL).
Secondary	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.	At the 24 hours and 72 hours after the first infusion of Neu2000KWL.
Secondary	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	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).
Secondary	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	The 5th day of study (which corresponds to 48 hours after finished treatment using Neu2000KWL).
Secondary	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)	5 day, 14 day, or discharge within 14 days, and 90 days after 1st infusion of Neu2000KWL
Secondary	Verification of difference between groups of Cumulative value of blood S100beta from 6th infusion after 1st infusion of Neu2000KWL.	Cumulative blood concentration of S100beta .	The 4th day of study (which corresponds to finished 6th infusion of Neu2000KWL).