This trial is active, not recruiting.

Conditions cardiac arrest, reperfusion injury
Sponsor Virginia Commonwealth University
Collaborator American Heart Association
Start date September 2013
End date July 2016
Trial size 40 participants
Trial identifier NCT01944605, HM15326


Out-of-hospital cardiac arrest (CA) is a leading public health problem causing nearly one third of a million deaths annually in the US, accounting for half of all cardiovascular deaths and surpassing deaths from stroke, heart failure, and breast and lung cancer combined. Twenty to fifty percent of CA patients (pts) can be resuscitated initially but many die before hospital discharge or suffer permanent neurologic damage. Therapeutic hypothermia (TH) improves survival and neurological outcomes. Despite aggressive, targeted post arrest management, including TH, approximately 50% of pts die before leaving the hospital due to global ischemia-reperfusion injury (IRI) known as the "post arrest syndrome", 1 which is a sepsis-like state characterized by elevated markers of cellular inflammation and injury. It is believed that TH works by decreasing the body's basal metabolic rate (BMR) and attenuating the systemic inflammatory response (SIR). However, specific triggers of the intense pro-inflammatory response are unclear. This "gap" in knowledge must be closed to identify targeted therapy to decrease IRI and improve outcomes.

Blood flow to the gut is decreased markedly and intestinal tissue becomes ischemic during CA and CPR, particularly when vasoconstrictor drugs such as epinephrine, are given. IRI of the intestine increases intestinal permeability leading to intestinal microbial translocation and endotoxin release that can stimulate and perpetuate systemic inflammation and cause subsequent multi-organ dysfunction. Endotoxin also increases body temperature and energy expenditure and may attenuate TH induced reductions in BMR and hence, decrease efficacy. The purpose of this novel pilot study is to detect systemic endotoxin release following CA in humans and determine association with cytokine activation, and BMR alterations during TH.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Observational model cohort
Time perspective prospective
Cardiac Arrest subjects with Return Of Spontaneous Circulation (ROSC) and undergoing treatment with Therapeutic Hypothermia will undergo sampling of blood, stool, and expired gas data at physiologically predetermined time points.

Primary Outcomes

Detection of Endotoxin Activity
time frame: 48 hours

Secondary Outcomes

Detection of sCD14
time frame: 48 hours
Detection of stool lactoferrin and stool α1-antitrypsin
time frame: 48 hours
Detection and quantification of inflammatory cytokines
time frame: 48 hours
BMR measurement elevation
time frame: 48 hours

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: Adult, Cardiac Arrest with ROSC receiving Therapeutic Hypothermia- Exclusion Criteria: - Age < 18 - Cardiac Arrest of traumatic etiology - Known to be pregnant - Prisoner

Additional Information

Official title Intestinal Ischemia as a Stimulus for Systemic Inflammatory Response After Cardiac Arrest
Principal investigator Mary Ann Peberdy, M.D.
Description Hypothesis 1 Intestinal ischemia during and following Caridac Arrest leads to increased gut permeability and endotoxin release that stimulates the Systemic Inflammatory Response that is responsible for subsequent death and disability after resuscitation. Hypothesis 2: Different degrees of systemic endotoxin activity variably affect Basic Metabolic Rate during Therapeutic Hypothermia Serial samples of blood, stool and expired gas will be measured at predetermined timepoints after ROSC from cardiac arrest.
Trial information was received from ClinicalTrials.gov and was last updated in January 2016.
Information provided to ClinicalTrials.gov by Virginia Commonwealth University.