Mitochondrial DNA as a Biomarker of Sepsis Severity (MBOSS)

Mitochondria are organelles (a specialized subunit of a cell) responsible for providing cells with energy. For reasons not yet understood, mitochondria will release their DNA into blood in response to cellular injury or cell death.

With a simple blood draw, investigators can measure the amount of mitochondrial DNA in a patient's blood.

The investigators' hypothesis, is that mitochondrial DNA can be used as a surrogate marker of cellular injury to predict patient outcomes. The investigators intend to test their hypothesis by measuring mitochondrial DNA in adult patients presenting to the Emergency Department with sepsis (a life-threatening condition due to an infection) and observing their hospital course.

Study Overview

• Status: Completed
• Conditions: Sepsis; Septic Shock; Severe Sepsis; Infection; Sepsis Syndrome

Detailed Description

Despite the advances of modern medicine, sepsis persists as one of the leading causes of death in the United States and poses a significant burden on U.S. health care, accounting for more than $24 billion of total hospital costs in 2013. The high mortality and cost of treating sepsis at least partially stems from the consequences of delayed diagnosis. Unfortunately, this delay is attributable to the broad clinical manifestations of the syndrome and the absence of a specific test for sepsis.

Realizing this, The Society of Critical Care Medicine and the European Society of Intensive Care Medicine have released guidelines emphasizing the need for diagnostic approaches aimed at the early detection of sepsis. The hope is that early recognition will allow for more aggressive upfront management thereby improving patient outcomes.

In 2013, Nakahira et al showed that circulating cell-free mitochondrial DNA levels are associated with sepsis and mortality in patients admitted to the ICU. In contrast to that study, the purpose here is to determine whether circulating cell-free mitochondrial DNA and other biomarkers are associated with the severity of sepsis and 28-day mortality in patients presenting to the ED with sepsis.

To accomplish this task, the investigators intend to prospectively collect specimens from patients presenting to NYP-Weill Cornell and NYP-Brooklyn Methodist with suspected sepsis.

• Study Type: Observational
• Enrollment (Actual): 1304

Contacts and Locations

• Study Contact: Name: John S Harrington, MD; Phone Number: 212-746-5454; Email: jsh9012@med.cornell.edu
• Study Contact Backup: Name: Edward J Schenck, MD; Phone Number: 646-962-2333; Email: ejs9005@med.cornell.edu

Study Locations

• United States
  • New York
    • Brooklyn, New York, United States, 11215
      • New York-Presbyterian Brooklyn Methodist Hospital
    • New York, New York, United States, 10065
      • New York Presbyterian/Weill Cornell Medicine

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

We intend to study patients presenting to the NYP-Weill Cornell Medicine Emergency Department and the NYP-Brooklyn Methodist Emergency Department.

Description

Inclusion Criteria:

• Adults presenting to the Emergency Department with suspected sepsis.

Exclusion Criteria:

• Pregnancy.
• Patients with limitations of care at the time of specimen collection.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
NYP-WCM; The NYP-WCM cohort will consist of patients presenting to the NewYork-Presbyterian/Weill Cornell Medicine Emergency Department with suspected sepsis.
NYP-BMH; The NYP-BMH cohort will consist of patients presenting to the NewYork-Presbyterian Brooklyn Methodist Hospital Emergency Department with suspected sepsis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospital Mortality	All-Cause	60 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Association with severity of illness as determined by qSOFA Score	qSOFA	3 Days
Association with severity of illness severity of illness as determined by MEDS Score	MEDS Score	3 Days
Association with severity of illness as determined by SOFA Score	SOFA Score	3 Days
Need for Supportive Measures	NIPPV, Mechanical Ventilation, Vasopressors, CVVHD, iNO, ECMO	Up to 60 Days
ICU-Free Days	Number of days free from ICU Admission	28 Days
Triage Decision	If the patient was discharged home or admitted to the floor, a step-down unit, or an ICU	3 Days

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); New York Presbyterian Hospital; New York Presbyterian Brooklyn Methodist Hospital
• Investigators: Principal Investigator: John Harrington, MD, Weill Medical College of Cornell University

Publications and helpful links

General Publications

• Nakahira K, Kyung SY, Rogers AJ, Gazourian L, Youn S, Massaro AF, Quintana C, Osorio JC, Wang Z, Zhao Y, Lawler LA, Christie JD, Meyer NJ, Mc Causland FR, Waikar SS, Waxman AB, Chung RT, Bueno R, Rosas IO, Fredenburgh LE, Baron RM, Christiani DC, Hunninghake GM, Choi AM. Circulating mitochondrial DNA in patients in the ICU as a marker of mortality: derivation and validation. PLoS Med. 2013 Dec;10(12):e1001577; discussion e1001577. doi: 10.1371/journal.pmed.1001577. Epub 2013 Dec 31.
• Torio CM, Moore BJ. National Inpatient Hospital Costs: The Most Expensive Conditions by Payer, 2013. 2016 May. In: Healthcare Cost and Utilization Project (HCUP) Statistical Briefs [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2006 Feb-. Statistical Brief #204. Available from http://www.ncbi.nlm.nih.gov/books/NBK368492/

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2017
• Primary Completion (Actual): December 22, 2020
• Study Completion (Actual): December 22, 2020

Study Registration Dates

• First Submitted: March 3, 2017
• First Submitted That Met QC Criteria: March 10, 2017
• First Posted (Actual): March 13, 2017

Study Record Updates

• Last Update Posted (Actual): February 24, 2023
• Last Update Submitted That Met QC Criteria: February 22, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Biomarker; Prognosis; Emergency Department; Intensive Care Unit; Mortality; Triage; Lactate; Mitochondrial DNA; Organ Dysfunction
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Inflammation; Shock; Sepsis; Toxemia; Systemic Inflammatory Response Syndrome
• Other Study ID Numbers: 1605017267; R01HL055330 (U.S. NIH Grant/Contract); P01HL108801 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Upon reasonable request, de-identified participant data will be able available to individuals six-months after publication of all data.

Drug and device information, study documents

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