Out-of-hospital Cardiac Arrest (OHCA) Biomarkers

May 7, 2020 updated by: University of Florida

Predicting Neurological Outcome Following Out of Hospital Cardiac Arrest (OHCA) by Quantitative Measurement of Serial Serum Biomarkers of Brain Injury.

Few early prognostic indicators are currently available for patients' families and clinicians following out of hospital cardiac arrest (OHCA), and blood biomarkers may be of prognostic value in these cases. Brain tissue is highly dependent upon aerobic respiration, and oxygen deprivation result in irreversible neuronal cell injury. Peptides released into the blood by injured neuronal cells can be measured to estimate degree of injury, and potentially predict long term neurological outcome.

Study Overview

Detailed Description

Aggressive treatment for patients with out-of-hospital cardiac arrest (OHCA) can result in return of spontaneous circulation (ROSC). However, prognosis for these patients remains poor, with low rates of survival to hospital admission and low rates of survival to hospital discharge. Furthermore, due to the exquisite sensitivity to hypoxic injury of neural tissue (dependent on aerobic respiration) relative to that of cardiac muscle, patients for whom ROSC can be obtained often suffer devastating neurological injury, with potential poor long-term neurological outcome. In some ischemic processes, for example, myocardial infarction, rapid measurement of cardiac biomarkers (e.g. Troponin isoform) is invaluable to current diagnosis and management. However, with regards to ischemic brain injury, there is currently no rapid, definitive diagnostic test to prognosticate outcome in OHCA. Biomarkers measurable in blood would have vital applications in prognosis and clinical research of neurological outcome in OHCA.

Other groups have studied the neurological predictive values of biomarkers after OHCA. A variety of proteins including S100B, neuron-specific enolase, and G-FAP, co-peptin, Tau, neurofilament light/ heavy chain, and secretoneurin have been proposed as potential biomarkers of neurological outcome at OHCA. Unfortunately, many of these have been shown to have several drawbacks. For example, some lack specificity due to being released during resuscitation (e.g., S100B is found extracerebrally in muscle, adipocytes, and chondrocytes, creating a confounding factor in CA patients receiving chest compressions). Others have lacked sufficient sensitivity in the prognosticating of neurological outcome (ref). Furthermore, there is a paucity of human studies in cardiac arrest on newer biomarkers that have been studied in other acute brain injury disease processes that could potentially serve as candidate biomarkers predicting neurological outcome at post cardiac arrest hypoxic brain injuries. Biomarkers such as UCH-L1, SBDP, and MBP have not been studied in a OHCA cohort.

The Investigator therefore propose a prospective, observational study in which the investigator will incorporate a minimally invasive and minimal risk measurement of blood biomarkers at time of ROSC. This would be done by drawing blood at ROSC (0-59mins), and additional blood draws at hours 6, 12, 18, 24, 48, 72, and on day 4, 5, and 6. The Investigator will then determine whether biomarker levels correlates with survival to hospital admission, survival to hospital discharge, and functional neurologic outcome at discharge and at 6 months. The Investigator intend to sample patients that present to the emergency department with non-CA chest pain in our study as well, which will allow us to draw stable inferences.

Study Type

Observational

Enrollment (Actual)

32

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Florida
      • Gainesville, Florida, United States, 32611
        • Univeristy of Florida

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

The study population will include all adult patients (≥ 18 years of age) with non-traumatic out of hospital cardiac arrest. Exclusions will include patients with advanced directives precluding resuscitation, traumatic cardiac arrest, and irreversible signs of death (e.g. rigor mortis). A matched control population will include hemodynamically stable patients who present to the ED with chest pain that is not of cardiac etiology (non-traumatic chief complaints). Blood draws in this cohort will be collected as per protocol and will end upon the termination of medical care or as per protocol - whichever is of the least duration.

Description

Inclusion Criteria:

- >18 years old

Study cohort:

  • Non-traumatic out of hospital cardiac arrest
  • Control cohort:
  • Chest pain of non-cardiac etiology

Exclusion Criteria:

Both cohorts:

  • Females of child bearing age with positive pregnancy test
  • Neurodegenerative disease or other neurological disorder (dementia, Parkinson's disease, multiple sclerosis, seizure disorder, or brain tumours)
  • History of neurosurgery within the last 30 days Acute brain injury within the last 30 days (ischemic/ haemorrhagic stroke, traumatic brain injury) Subject is anemic OR donated blood within the last 8 weeks OR has a hematological disorder that requires transfusions Subject has history of liver failure OR renal failure

Study cohort:

Advanced directives against resuscitation Traumatic cardiac arrest In hospital cardiac arrest Failure to attain ROSC + visible signs of death (livor mortis, rigor mortis)

Control cohort:

EKG changes: New ST-elevation consistent with myocardial infarction NSTEMI Hemodynamically unstable

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Cardiac Arrest cohort
adult patients (≥ 18 years of age) with non-traumatic out of hospital cardiac arrest
Blood draws will be collected via venipuncture or IV at hours 0, 6, 12, 18, 24, 48, 72, 96, 120, 144 (10 draws total). Each draw would be approximately 20 mL of blood (but no less than 10 mL).
Control cohort
matched control population will include hemodynamically stable patients who present to the ED with chest pain that is not of cardiac etiology (non-traumatic chief complaints).
Blood draws will be collected via venipuncture or IV at hours 0, 6, 12, 18, 24, 48, 72, 96, 120, 144 (10 draws total). Each draw would be approximately 20 mL of blood (but no less than 10 mL).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
In-hospital mortality
Time Frame: 1 year
Higher blood biomarker levels will correlate with reduced rate of survival to hospital admission, survival to hospital discharge, and 6-month survival.
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Functional neurological outcome at discharge
Time Frame: 1 year
Higher blood biomarker levels will correlate with higher degree of neurological impairment as measured by Cerebral Performance Category.
1 year
Functional neurological outcome at 6 months after discharge
Time Frame: 1 year
Higher blood biomarker levels will correlate with higher degree of neurological impairment as measured by Cerebral Performance Category.
1 year

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Influence of renal and liver disease on blood biomarker(s) level post-OHCA
Time Frame: 1 year
Renal and liver disease may affect levels of protein biomarkers after cardiac arrest
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Joseph A Tyndall, MD, MPH, Chairman Department Emergency Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

May 26, 2017

Primary Completion (ACTUAL)

January 28, 2020

Study Completion (ACTUAL)

January 28, 2020

Study Registration Dates

First Submitted

April 7, 2017

First Submitted That Met QC Criteria

April 7, 2017

First Posted (ACTUAL)

April 13, 2017

Study Record Updates

Last Update Posted (ACTUAL)

May 8, 2020

Last Update Submitted That Met QC Criteria

May 7, 2020

Last Verified

May 1, 2020

More Information

Terms related to this study

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

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Brain Injuries

Clinical Trials on blood draw

3
Subscribe