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

Phase 2

• Conditions: Cardiac Arrest
• Interventions: Drug: Neu2000KWL High-dose group; Drug: Neu2000KWL Low-dose group; Drug: Placebo

• Registration Number: NCT03651557
• Lead Sponsor: GNT Pharma

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.

Study Timeline

• Study First Submitted: 2018-07-26
• Status Verified: 2018-08
• Study First Submitted QC: 2018-08-28
• Study First Posted: 2018-08-29
• Study Start: 2018-11-29
• Last Update Submitted: 2019-03-05
• Last Update Posted: 2019-03-06
• Primary Completion: 2021-05
• Study Completion: 2021-05

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 150

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Neu2000KWL high dose	Neu2000KWL High-dose group	-
Neu2000KWL low dose	Neu2000KWL Low-dose group	-
saline	Placebo	-

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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.
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)
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 .
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
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
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)

Trial Locations

Locations (6)

Kyungpook National University Hospital; 🇰🇷 Daegu, Korea, Korea, Republic of

Soonchunhyang University Bucheon Hospital; 🇰🇷 Bucheon, Korea, Republic of

Pusan National University Hospital; 🇰🇷 Busan, Korea, Republic of

Samsung Medical Center; 🇰🇷 Seoul, Korea, Republic of

Chonnam National University Hospital; 🇰🇷 Gwangju, Korea, Republic of

Gangnam Severance Hospital; 🇰🇷 Seoul, Korea, Republic of