Clinical Trial of Sodium Nitrite for Out of Hospital Cardiac Arrest (SNOCAT)

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

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.

Study Overview

• Status: Completed
• Conditions: Out-Of-Hospital Cardiac Arrest
• Intervention / Treatment: Drug: Placebo; Drug: sodium nitrite 45 mg; Drug: sodium nitrite 60 mg

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.

• Study Type: Interventional
• Enrollment (Actual): 1502
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Francis Kim, MD, University of Washington

Publications and helpful links

General Publications

• Kim F, Maynard C, Dezfulian C, Sayre M, Kudenchuk P, Rea T, Sampson D, Olsufka M, May S, Nichol G. Effect of Out-of-Hospital Sodium Nitrite on Survival to Hospital Admission After Cardiac Arrest: A Randomized Clinical Trial. JAMA. 2021 Jan 12;325(2):138-145. doi: 10.1001/jama.2020.24326.

Study record dates

Study Major Dates

• Study Start (Actual): February 8, 2018
• Primary Completion (Actual): December 31, 2019
• Study Completion (Actual): April 30, 2020

Study Registration Dates

• First Submitted: February 12, 2018
• First Submitted That Met QC Criteria: March 1, 2018
• First Posted (Actual): March 2, 2018

Study Record Updates

• Last Update Posted (Actual): May 24, 2023
• Last Update Submitted That Met QC Criteria: April 27, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Arrest; Out-of-Hospital Cardiac Arrest
• Other Study ID Numbers: 51605; R01HL129722 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No