Effect of Out-of-Hospital Sodium Nitrite on Survival to Hospital Admission After Cardiac Arrest: A Randomized Clinical Trial | Cardiology | JAMA | JAMA Network
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Original Investigation
January 12, 2021

Effect of Out-of-Hospital Sodium Nitrite on Survival to Hospital Admission After Cardiac Arrest: A Randomized Clinical Trial

Author Affiliations
  • 1Department of Medicine, School of Medicine, University of Washington, Seattle
  • 2Department of Health Services, School of Public Health, University of Washington, Seattle
  • 3Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
  • 4Department of Emergency Medicine, School of Medicine, University of Washington, Seattle
  • 5Department of Biostatistics, School of Public Health, University of Washington, Seattle
JAMA. 2021;325(2):138-145. doi:10.1001/jama.2020.24326
Key Points

Question  Does the use of sodium nitrite during resuscitation from out-of-hospital cardiac arrest improve survival to hospital admission?

Finding  In this phase 2 randomized clinical trial that included 1502 patients, out-of-hospital administration with 45 mg or 60 mg of sodium nitrite during active resuscitation by paramedics, compared with placebo, did not significantly improve survival to hospital admission (41% for the 45-mg dose and 43% for the 60-mg dose vs 44% for placebo).

Meaning  These findings do not support the use of sodium nitrite during resuscitation from out-of-hospital cardiac arrest.

Abstract

Importance  Therapeutic delivery of sodium nitrite during resuscitation improved survival in animal models of cardiac arrest, but efficacy has not been evaluated in clinical trials in humans.

Objective  To determine whether parenteral administration of sodium nitrite given by paramedics during resuscitation for out-of-hospital cardiac arrest improved survival to hospital admission.

Design, Setting, and Participants  Double-blind, placebo-controlled, phase 2 randomized clinical trial including 1502 adults in King County, Washington, with out-of-hospital cardiac arrest from ventricular fibrillation or nonventricular fibrillation. Patients underwent resuscitation by paramedics and were enrolled between February 8, 2018, and August 19, 2019; follow-up and data abstraction were completed by December 31, 2019.

Interventions  Eligible patients with out-of-hospital cardiac arrest were randomized (1:1:1) to receive 45 mg of sodium nitrite (n = 500), 60 mg of sodium nitrite (n = 498), or placebo (n = 499), which was given via bolus injection by the paramedics as soon as possible during active resuscitation.

Main Outcomes and Measures  The primary outcome was survival to hospital admission and was evaluated with 1-sided hypothesis testing. The secondary outcomes included out-of-hospital variables (rate of return of spontaneous circulation, rate of rearrest, and use of norepinephrine to support blood pressure) and in-hospital variables (survival to hospital discharge; neurological outcomes at hospital discharge; cumulative survival to 24 hours, 48 hours, and 72 hours; and number of days in the intensive care unit).

Results  Among 1502 patients with out-of-hospital cardiac arrest who were randomized (mean age, 64 years [SD, 17 years]; 34% were women), 99% completed the trial. Overall, 205 patients (41%) in the 45 mg of sodium nitrite group and 212 patients (43%) in the 60 mg of sodium nitrite group compared with 218 patients (44%) in the placebo group survived to hospital admission; the mean difference for the 45-mg dose vs placebo was −2.9% (1-sided 95% CI, −8.0% to ∞; P = .82) and the mean difference for the 60-mg dose vs placebo was −1.3% (1-sided 95% CI, −6.5% to ∞; P = .66). None of the 7 prespecified secondary outcomes were significantly different, including survival to hospital discharge for 66 patients (13.2%) in the 45 mg of sodium nitrite group and 72 patients (14.5%) in the 60 mg of sodium nitrite group compared with 74 patients (14.9%) in the placebo group; the mean difference for the 45-mg dose vs placebo was −1.7% (2-sided 95% CI, −6.0% to 2.6%; P = .44) and the mean difference for the 60-mg dose vs placebo was −0.4% (2-sided 95% CI, −4.9% to 4.0%; P = .85).

Conclusions and Relevance  Among patients with out-of-hospital cardiac arrest, administration of sodium nitrite, compared with placebo, did not significantly improve survival to hospital admission. These findings do not support the use of sodium nitrite during resuscitation from out-of-hospital cardiac arrest.

Trial Registration  ClinicalTrials.gov Identifier: NCT03452917

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