Clinical trial NCT03077672: Mitochondrial DNA as a Biomarker of Sepsis Severity
Official title: Mitochondrial DNA as a Biomarker of Sepsis Severity
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Sepsis Syndrome
Sepsis
Severe Sepsis
Septic Shock
Infection
Keywords: Mitochondrial DNA
Lactate
Mortality
Emergency Department
Intensive Care Unit
Triage
Organ Dysfunction
Biomarker
Prognosis
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
Collaborators: name: New York Presbyterian Hospital
name: New York Presbyterian Brooklyn Methodist Hospital
name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2017-03-13
Enrollment: 1304
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Hospital Mortality
timeFrame: 60 Days
Secondary outcomes:
measure: Association with severity of illness as determined by qSOFA Score
timeFrame: 3 Days
measure: Association with severity of illness severity of illness as determined by MEDS Score
timeFrame: 3 Days
measure: Association with severity of illness as determined by SOFA Score
timeFrame: 3 Days
measure: Need for Supportive Measures
timeFrame: Up to 60 Days
measure: ICU-Free Days
timeFrame: 28 Days
measure: Triage Decision
timeFrame: 3 Days
Other outcomes:
Locations:
city: Brooklyn
country: United States
facility: New York-Presbyterian Brooklyn Methodist Hospital
state: New York
city: New York
country: United States
facility: New York Presbyterian/Weill Cornell Medicine
state: New York
Study officials:
affiliation: Weill Medical College of Cornell University
name: John Harrington, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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/
citation: 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.