Inhaled Nitric Oxide After Out-of-Hospital Cardiac Arrest

• Status: Terminated
• Trial end date: 2020-06-02
• Target enrollment: 0
• Participant gender: All

Summary

Phase II double blind (participants and investigator) placebo controlled randomized (1:1) clinical trial of inhaled nitric oxide (iNO) 20 ppm administered over 12h beginning as soon as possible but within 4 h of return of spontaneous circulation (ROSC) from out-of-hospital cardiac arrest (OHCA). Planned enrollment is 180 subjects over 48 months at University of Pittsburgh Medical Center (UPMC) Hospitals with randomization stratified in blocks of 8. Recruitment will be performed under exception from informed consent (EFIC) to facilitate early enrollment and treatment. The study will have a pre-specified safety analysis at the mid-point (after 1 year or 60 patients whichever occurs first). Subjects will be screened by members of the University of Pittsburgh post-cardiac arrest service (PCAS), all of whom will serve as the study co-investigators, and the Research Coordinators. Notification of inclusion under EFIC will be performed as soon as possible by a member of the study team generally to a surrogate as the subjects will be comatose after OHCA.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Cameron Dezfulian
• Collaborator: Mallinckrodt
• Treatments: Nitric Oxide

Criteria

Inclusion Criteria:

• Intubated and comatose adult (>18 yo) resuscitated from out-of-hospital cardiac arrest (OHCA)*

*Cardiac arrest within an emergency department or outpatient medical center will be included). OHCA includes Emergency Medical Service (EMS) witnessed cardiac arrest.

• Return of spontaneous circulation (ROSC) within 40 min of CPR initiation

• Full Outline of Unresponsiveness (FOUR) Brainstem score ≥ 2 (i.e. patient must have pupil OR corneal reflex at the time of ED presentation or within 1h if sedation/neuromuscular blockade clouds the picture)

Exclusion Criteria:

• Traumatic etiology of OHCA

• Prisoner

• Known pregnancy (beta-human chorionic gonadotropin screening is NOT REQUIRED for enrollment in women of appropriate age)

• Hemodynamic instability defined as >1 recurrent arrest prior to enrollment OR inability to maintain mean arterial blood pressure (MAP) > 65 using vasopressors and inotropes (ie actively up titrating medications or giving fluid bolus)

• Head CT grey-white ratio < 1.2; Head CT is NOT REQUIRED prior to enrollment

• Fixed and dilated pupils without another explanation

• Known intracranial hemorrhage or acute cerebral infarction; Head CT is NOT REQUIRED prior to enrollment

• Malignant EEG upon presentation defined as: myoclonic status epilepticus, non-convulsive status epilepticus, generalized periodic epileptiform discharges. EEG screening is NOT REQUIRED prior to enrollment

• ROSC >3h from time of ED arrival (treatment allocation must be within 4h so anything that will prevent this is reason for exclusion)

• Alert and interactive patient with minimal evidence of neurologic injury

• Plan to extubate within 12 hours

• Post-cardiac arrest service (PCAS) physician opinion that patient will die with >95% likelihood. This may be based on:

• Multiple medical comorbidities

• Late discovery of don not resuscitate (DNR) or advanced directive

• Terminal diagnosis (other than OHCA; may have caused OHCA)

• Clinical judgement based on current exam and data

• Patient is known to be taking phosphodiesterase type 5 (PDE5) inhibitors, soluble guanylyl cyclase (sGC) stimulator, or has a known diagnosis of Chronic thromboembolic pulmonary hypertension (CTEPH), pulmonary hypertension (PAH), or erectile dysfunction

• Known enrollment in another acute interventional study.