Clinical Trial of Sodium Nitrite for Out of Hospital Cardiac Arrest

Phase 2

Completed

Conditions: Out-Of-Hospital Cardiac Arrest

Interventions: Drug: Placebo
Drug: sodium nitrite 45 mg
Drug: sodium nitrite 60 mg

Registration Number: NCT03452917

Lead Sponsor: University of Washington

Brief Summary: In this clinical study, a total of 1500 patients with out-of-hospital cardiac arrest in Seattle/King County will be enrolled. This will be a randomized clinical trial and patients will receive either two different doses of IV sodium nitrite (45 mg or 60 mg) or placebo during resuscitation in the field by paramedics. The primary outcome will be proportion of patients surviving to hospital admission.

Detailed Description: The hemodynamic effects of the optimal dose of IV nitrite administered in patients with cardiac arrest are unknown. A significant negative hemodynamic effect from nitrite would decrease the proportion of patients admitted to the hospital, increase rate of re-arrest, or increase the need for vasopressor support in the field. In Seattle/King County, typically 40% of out-of-hospital cardiac arrest patients attended to by paramedics have Return of spontaneous circulation (ROSC) and are admitted to the hospital. In this study, 1500 patients with out-of-hospital cardiac arrest who are undergoing resuscitation by paramedics will be randomized to receive placebo (n=500) or 45 mg IV (n=500) or 60 mg dose (n=500) of sodium nitrite. The study will have 80% power to detect an absolute increase in hospital admission rate of 8% (1-sided .05 level test for each of the two comparisons (45 mg vs placebo and 60 mg vs placebo, no adjustment for multiple comparisons), with a hospital admission rate of 40% in the placebo group and with one interim analysis and stopping only for potential futility and/or harm). The investigators will examine the proportion of patients who survive to discharge as a secondary measure of efficacy.

Patients will be eligible for this study if:

1. Intravenous access (IV)/intraosseous access(IO)

2. Cardiac arrest, either Ventricular Fibrillation (VF) or non-VF patients receiving Advanced Cardiac Life Support (ACLS) by Seattle/King County paramedics.

3. Age 18 years or older

4. Comatose

Exclusion Criteria

1. Traumatic cause of cardiac arrest

2. Prisoner, pregnancy, age less than 18 (special population/vulnerable population)

3. Known DNAR

4. Drowning as cause of arrest.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1502

Inclusion Criteria

Cardiac arrest, either VF or non-VF, patients receiving ACLS by paramedics
IV or IO access
Comatose

Exclusion Criteria

traumatic cause of cardiac arrest
prisoner, pregnancy
known DNAR

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	2 ml of normal saline (n=500)
sodium nitrite	sodium nitrite 45 mg	45 mg IV of sodium nitrite (n=500) or 60 mg IV sodium nitrite (n=500) given during active resuscitation from out of hospital cardiac arrest.
sodium nitrite	sodium nitrite 60 mg	45 mg IV of sodium nitrite (n=500) or 60 mg IV sodium nitrite (n=500) given during active resuscitation from out of hospital cardiac arrest.

Primary Outcome Measures

Name	Time	Method
Number of Participants Who Survived to Hospital Admission	within 24 hours after out of hospital cardiac arrest	Patient has sustained pulse at arrival to the emergency department

Secondary Outcome Measures

Name	Time	Method
Survival to 24 Hours	within first 24 h after hospital admission	Patient is alive after the first 24 hours after admission to the hospital
Number of Days in ICU	Within first 3 months of hospital admission	Number of days the patient is admitted to the Intensive Care Unit
Survival to Discharge	within 3-6 months after cardiac arrest	Patient alive at time of discharge from hospital
Re-arrest	before hospital arrival	Patient loses pulses during transport to the hospital. Event occurs before admission to hospital.
Survival to 48 Hours After Admission to Hospital	within first 48 hours after admission to hospital	Patient is alive after first 48 hours after admission to the hospital
Survival to 72 Hours After Admission to Hospital	within first 72 hours after admission to hospital	Patient is alive after first 72 hours after admission to the hospital