Use of Sodium Nitrite in Out of Hospital Cardiac Arrest

Overview

Cardiac arrest is a medical problem with major adverse health impacts.  In the United States about 225,000 people per year die from cardiac arrest before reaching the hospital.  Many more never leave the hospital, or will become severely disabled because the brain and other organs are injured due to a lack of blood and oxygen.  Some patients will wake up and recover.  However, many patients resuscitated from cardiac arrest never awaken, despite the excellent care they receive.  In other words, these patients never regain enough neurologic function to allow them to follow commands or to have comprehensible speech.

Effective treatments to protect the brain and other organs from the damage that accompanies cardiac arrest would allow more patients to awaken after cardiac arrest and survive to hospital discharge.  To date, studies using various drugs have failed to improve outcome after cardiac arrest.  Researchers continue to look for new therapies that may improve the patient's chance of improved neurologic outcome and survival.

Studies on animals have shown that sodium nitrite, given during cardiac arrest, may improve outcome.  University of Washington researchers based at Harborview Medical Center will conduct a large study of sodium nitrite in patients who have out of hospital cardiac arrest.  It is thought that giving sodium nitrite outside the hospital may improve neurologic outcome and survival in this group of patients. 

The "Use of Sodium Nitrite in Out of Hospital Cardiac Arrest" study is an experiment being conducted under the U.S. Food and Drug Administration (FDA) "emergency waiver of consent" guidelines.  These guidelines allow people, in specific circumstances, to be enrolled in a study without their consent.  Typically, federal regulations do not allow subjects to be enrolled in a study without their informed consent or that of their next of kin.  In certain limited situations, however, such as emergency medicine research, the FDA allows studies to be conducted without prior consent.  In such circumstances, the FDA requires the following criteria be met.

  • Patient cannot give consent
  • Patient may benefit from the research
  • Research project could not be done without this waiver of consent
  • Researcher agrees to inform patient or family at a later time
  • Researcher asks the community
  • University of Washington Institutional Review Board (IRB) approved the study

The first part of this trial will enroll 100 patients who receive sodium nitrite.  Investigators will examine whether the drug dosage given during cardiac arrest produces therapeutic blood levels.  The larger study, to follow, will enroll 1,000 patients treated for cardiac arrest by the Seattle Fire Department.  Half of these patients will receive sodium nitrite and half will receive a placebo.

Known potential risks to patients in this trial include the risk of decreased blood pressure.  Safety measures have been built into the study to minimize that risk.  In the studies cited above no such complications have been reported.  However, there may be unknown or unexpected risks.

We have conducted surveys to gauge interest and the community's willingness to participate in this trial in which informed consent cannot be obtained.  More that 82 percent of respondents supported this study being conducted in Seattle and nearly 66 percent of surveyed individuals said they would be willing to participate. About 50 percent of non-white respondents would be willing to be part of the study.

For more information about this study, please view the consent form (under the "consent form" tab) or call us at 206-521-1588.  Voicemails will be returned. 

Opting out of this study

Patients who do not want to participate in this study can request an opt-out bracelet to wear. These rubber bracelets may be obtained by calling the research coordinator.  If a patient suffers an out-of-hospital cardiac arrest and the arriving paramedics see that the patient is wearing this opt out bracelet, the patient will not be enrolled.

Frequently Asked Questions

Research Materials

  • Information Sheet
  • Consent Form
  • HIPPA Form

Community Consultation information

  • Press Release
  • Random Digit Dialing Survey
  • Bite of Seattle Community Event Survey
  • Union Gospel Mission Community Survey

Publications

Dezfulian C, Shiva S, Alekseyenko A, Pendyal A, Beiser DG, Munasinghe JP, et al. Nitrite therapy after cardiac arrest reduces reactive oxygen species generation, improves cardiac and neurological function, and enhances survival via reversible inhibition of mitochondrial complex I. Circulation. 2009;120(10):897-905.

Jung KH, Chu K, Ko SY, Lee ST, Sinn DI, Park DK, et al. Early intravenous infusion of sodium nitrite protects brain against in vivo ischemia-reperfusion injury. Stroke. 2006;37(11):2744-50.

Jung K-H, Chu K, Lee S-T, Park H-K, Kim J-H, Kang K-M, et al. Augmentation of nitrite therapy in cerebral ischemia by NMDA receptor inhibition. Biochemical and Biophysical Research Communications. 2009;378(3):507-12.

Dezfulian C, Alekseyenko A, Dave KR, Raval AP, Do R, Kim F, et al. Nitrite Therapy is Neuroprotective and Safe in Cardiac Arrest Survivors. Nitric Oxide. 2012;26(4):241-50.

Contact Us

Michele Olsufka RN, Research Coordinator – Seattle
Phone: 206-521-1588

Mailing address:
Harborview Medical Center
Department of Medicine/Division of Cardiology
325 9th Avenue
Box 359748
Seattle, WA 98104-2499

Obtaining an “informed consent” from victims of cardiac arrest is impossible as the participant is unconscious and the family is either not immediately available or extremely distraught.  To allow researchers to try to improve the survival rate of individuals suffering from a life-threatening condition, the US Food and Drug Administration (FDA) has issued guidelines for the consent to be waived in emergency circumstances, if the research has the prospect of direct benefit to the patient.  To conduct a study using an “emergency waiver of consent” the following circumstances must exist.

·         A life-threatening situation with unproven or unsatisfactory treatment where research is necessary to improve outcome.

·         Obtaining informed consent is not feasible because the patient is unresponsive and treatment must begin immediately.

·         Participation in research has the prospect of direct benefit because the situation necessitates an intervention, science supports the potential of direct benefit and the risks of the research are reasonable compared to the medical condition.

·         The research could not practicably be done without waiver of informed consent.

·         The potential therapeutic window is short (in the case of cardiac arrest, treatment needs to be given within minutes)

·         The researchers must develop informed consent procedures they will implement when it is possible to obtain consent.

·         An Institutional Review Board (IRB) must approve the study

 

This study meets these FDA requirements.  Participants or their legally authorized representative will be contacted as soon as possible after enrollment into the study.  The purpose of this contact will be to provide information about the study and in some cases, to ask permission for continued participation in the trial.  Continuation in the trial means allowing access to medical records. 

 

To inform as many people as possible before the research begins, the researchers are required to disclose to the public the nature, risks and benefits of the study. The researchers want to provide the community with information about this study and an opportunity for people to ask questions about the potential risks and benefits.  The researchers want to gather information from the community and inform as many people as possible about the study before, during, and after the research is conducted.  This is being done through a variety of means:

 

A.    The information provided in this website

 

B.  Random digit telephone survey

A random sample of 400 Seattle area households were contacted by phone and asked their opinion of waiver of consent and whether or not they would want the sodium nitrite treatment administered to them without their consent.

C.    Seattle event community survey

A sample of 242 attendees at the Bite of Seattle completed a questionnaire that asked their opinion of waiver of consent and whether or not they would want the sodium nitrite treatment administered to them without their consent.

D.  Union Gospel Mission community survey

A sample of 48 attendees at the Union Gospel Mission completed a questionnaire that asked their opinion of waiver of consent and whether or not they would want the sodium nitrite treatment administered to them without their consent.

Union