Intestinal Ischemia as a Stimulus for Systemic Inflammatory Response After Cardiac Arrest

Cardiac Arrest Clinical Trial

— TICA  

Official title:

Intestinal Ischemia as a Stimulus for Systemic Inflammatory Response After Cardiac Arrest

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01944605
• Other study ID #: HM15326
• Status: Completed
• Phase: N/A
• First received: September 12, 2013
• Last updated: October 5, 2017
• Start date: September 2013
• Est. completion date: March 30, 2014

Study information

• Verified date: October 2017
• Source: Virginia Commonwealth University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: March 30, 2014
• Est. primary completion date: March 30, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Adult, Cardiac Arrest with ROSC receiving Therapeutic Hypothermia-

Exclusion Criteria:

• Age < 18

• Cardiac Arrest of traumatic etiology

• Known to be pregnant

• Prisoner

Related Conditions & MeSH terms

• Cardiac Arrest
• Heart Arrest
• Ischemia
• Reperfusion Injury

Locations

Country	Name	City	State
United States	Virginia Commonwealth University	Richmond	Virginia

Sponsors (2)

Lead Sponsor	Collaborator
Virginia Commonwealth University	American Heart Association

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Detection of Endotoxin Activity	Endotoxin activity will be measured by the Endotoxin Activity Assay and values . of >0.4 EA units will be used as the "cut-off" for the presence of pathological endotoxin.	48 hours
Secondary	Detection of sCD14	To demonstrate activation of endotoxin by the immune system and "upstream" physiologic changes necessary for systemic endotoxemia to occur	48 hours
Secondary	Detection of stool lactoferrin and stool a1-antitrypsin	To demonstrate evidence of intestinal inflammation and permeability that can lead to endotoxemia and "downstream" cellular inflammatory responses responsible for end organ damage	48 hours
Secondary	Detection and quantification of inflammatory cytokines	To demonstrate an association with the primary outcome	48 hours
Secondary	BMR measurement elevation	To determine its association with endotoxemia and cytokine. BMR is being measured to determine if pts with higher levels of endotoxin and cytokines have higher BMR and therefore blunted therapeutic value of TH	48 hours