# Randomized clinical trial of sodium nitrite for out of hospital cardiac arrest

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2020 · $668,784

## Abstract

Abstract
Out-of-hospital cardiac arrest (OHCA) is a common and debilitating public health problem. Neurologic injury is
the major cause of morbidity and mortality in these patients with most resuscitated victims never regaining
consciousness. Despite advances in resuscitation, over 70% of those who have circulation restored after OHCA
die before hospital discharge. Therapies directed at heart and brain protection are needed to ameliorate many
of the biochemical/cellular changes during the post resuscitation phase, which ultimately lead to cell death. The
anion nitrite (NO2-) is converted to NO during hypoxia and during low pH, independent of NOS activity, making
NO2- an ideal drug to increase NO bioavailability during ischemia and early in reperfusion when there is critical
depletion. Therapeutic delivery of nitrite during ischemia or at time of reperfusion is cytoprotective in animal
models of cardiac arrest. In an ongoing single-center pilot randomized trial of sodium nitrite (1-14 mg) IV vs.
identically-appearing placebo in patients resuscitated from OHCA and transported to hospital, we found no
significant deleterious effect of nitrite on hemodynamics. We believe that administration of sodium nitrite is
feasible and not associated with serious adverse events in this population. These animal and human studies
demonstrate the potential promise of nitrite as a therapy during resuscitation to reduce neurologic injury and
improve survival.
The overall goal of this study is to determine whether the administration of sodium nitrite is safe and
efficacious during on going resuscitation for out-of-hospital cardiac arrest. We propose a two-stage
clinical trial. The first phase will be an open-label dose finding trial to determine the optimal sodium nitrite dose
to be administered at the time of resuscitation to achieve a plasma level of 10 M by hospital arrival. The
second phase will be a placebo-control, randomized trial of the optimal single dose of sodium nitrite delivered
during resuscitation to determine safety and efficacy. For both phases, all patients who have OHCA (both
ventricular fibrillation (VF) and non-VF) in Seattle in which paramedics attempt cardiac resuscitation and have
established IV access will be eligible. The primary safety outcome for the phase 2 trial will be survival to
hospital admission and the secondary efficacy outcome will be survival to discharge.

## Key facts

- **NIH application ID:** 9922344
- **Project number:** 5R01HL129722-05
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Francis Kim
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $668,784
- **Award type:** 5
- **Project period:** 2016-07-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9922344

## Citation

> US National Institutes of Health, RePORTER application 9922344, Randomized clinical trial of sodium nitrite for out of hospital cardiac arrest (5R01HL129722-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9922344. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*