Clinical Trial of Sodium Nitrite for Out of Hospital Cardiac Arrest

Study Overview
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Brief Summary
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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
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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: Intravenous access (IV)/intraosseous access(IO) Cardiac arrest, either Ventricular Fibrillation (VF) or non-VF patients receiving Advanced Cardiac Life Support (ACLS) by Seattle/King County paramedics. Age 18 years or older Comatose Exclusion Criteria Traumatic cause of cardiac arrest Prisoner, pregnancy, age less than 18 (special population/vulnerable population) Known DNAR Drowning as cause of arrest.

Official Title
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Randomized Clinical Trial of Sodium Nitrite for Out of Hospital Cardiac Arrest

Conditions
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Out-Of-Hospital Cardiac Arrest

Intervention / Treatment
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* Drug: Placebo
* Drug: sodium nitrite 45 mg
* Drug: sodium nitrite 60 mg


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>2 ml of normal saline (n=500) | Drug: Placebo<br>* 500 patients will 2 ml of normal saline<br>|
| Experimental: sodium nitrite<br>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. | Drug: sodium nitrite 45 mg<br>* 500 patients will receive 45 mg IV sodium nitrite<br>Drug: sodium nitrite 60 mg<br>* 500 patients will receive a dose of 60 mg IV sodium nitrite<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Survived to Hospital Admission | Patient has sustained pulse at arrival to the emergency department | within 24 hours after out of hospital cardiac arrest | 

Secondary Outcome Measures

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