Plasma Angiopoietin Levels in Children Following Cardiopulmonary Bypass

Congenital Heart Defects Clinical Trial

Official title:

Plasma Angiopoietin Levels in Children Undergoing Modified Ultrafiltration Following Cardiopulmonary Bypass

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01489475
• Other study ID #: 1107008778
• Status: Completed
• Phase: N/A
• First received: November 29, 2011
• Last updated: February 24, 2015
• Start date: November 2011
• Est. completion date: June 2013

Study information

• Verified date: October 2013
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial Summary

During cardiopulmonary bypass (CPB) after heart surgery, a child's blood is exposed to many foreign entities. These conditions trigger the body's inflammatory response which results in leaky capillaries, increased swelling and possibly organ dysfunction. Since the early 1990's, modified ultrafiltration (MUF) has been shown to decrease excess swelling, reduce bleeding, improve heart function, and decrease hospital length of stay. Angiopoietins are a family of proteins necessary for both normal and abnormal blood vessel formation. They also appear to play a role in capillary leak. Though MUF has been shown to improve clinical outcome following CPB, there continues to be conflicting reports whether this is a result of the filtration of inflammatory proteins or simply from excess fluid removal. Since angiopoietins appear to play a role in both inflammation and capillary leak, the investigators hypothesize that the benefit seen after MUF is also secondary to its ability to filter out these proteins, especially angiopoietin-2.

Description:

During cardiopulmonary bypass (CPB) for corrective or palliative congenital heart surgery, a child's blood is subjected to hemodilution, hypothermia, nonpulsatile blood flow and exposure to foreign and non-endothelialized surfaces. These non-physiologic conditions trigger the host's innate systemic inflammatory response which results in capillary leak, increased total body water and can lead to end organ dysfunction. Since the early 1990's, modified ultrafiltration (MUF) has been shown to decrease excess tissue edema, reduce postoperative bleeding, improve cardiac contractility, maintain hemodynamic stability, and decrease hospital length of stay. Angiopoietins are a family of vascular growth factors necessary for both normal and abnormal blood vessel formation and appear to play a role in capillary leak. Though MUF has been shown to improve clinical outcome following CPB, there continues to be conflicting reports whether this is a result of the filtration of inflammatory cytokines or simply excess fluid removal. Since angiopoietins appear to play a role in both inflammation and capillary leak, the investigators aim to determine whether MUF's clinical benefit is also secondary to its ability to filter out these molecules, more specifically angiopoietin-2.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: June 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 18 Years

Eligibility

Inclusion Criteria:

• Pediatric patients with congenital heart disease undergoing surgical intervention requiring cardiopulmonary bypass and modified ultrafiltration.

Exclusion Criteria:

• Any patients with congenital heart disease who will not require modified ultrafiltration.

Study Design

Observational Model: Case-Only, Time Perspective: Prospective

Related Conditions & MeSH terms

• Congenital Heart Defects
• Heart Defects, Congenital

Locations

Country	Name	City	State
United States	Yale Children's Hospital	New Haven	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
Yale University

Country where clinical trial is conducted

United States, 

References & Publications (1)

Lang SM, Syed MA, Dziura J, Rocco E, Kirshbom P, Bhandari V, Giuliano JS Jr. The effect of modified ultrafiltration on angiopoietins in pediatric cardiothoracic operations. Ann Thorac Surg. 2014 Nov;98(5):1699-704. doi: 10.1016/j.athoracsur.2014.06.053. E — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in pro- and anti-inflammatory protein levels after modified ultrafiltration	Modified ultrafiltration (MUF) is the process after cardiopulmonary bypass during which a filtration unit is added and blood is filtered and returned back to the patient. The goal of this project is to evaluate the effect of MUF on concentrations of Angiopoietin-2 (Ang-2) and IL 8, two known pro-inflammatory markers involved in capillary leakage, as well as Ang-1 and IL 10, two anti-inflammatory mediators. Levels will be drawn prior to bypass, after MUF and at ICU admission.	baseline to completion of MUF, on average 2 hours	No
Primary	Change from baseline in pro- and anti-inflammatory protein levels at ICU admission	Modified ultrafiltration (MUF) is the process after cardiopulmonary bypass during which a filtration unit is added and blood is filtered and returned back to the patient. The goal of this project is to evaluate the effect of MUF on concentrations of Angiopoietin-2 (Ang-2) and IL 8, two known pro-inflammatory markers involved in capillary leakage, as well as Ang-1 and IL 10, two anti-inflammatory mediators. Levels will be drawn prior to bypass, after MUF and at ICU admission.	baseline to ICU admission, on average 7 hours	No
Secondary	Biomarker correlation with patient outcome	The biomarkers will be compared to the age of patient, type of surgery performed as well as to post procedure outcome measurements to see if specific protein levels correlate with patient outcomes.	Duration of pediatric ICU admission, on average 7 days	No
Secondary	Pro- and anti-inflammatory protein presence in ultrafiltration fluid	MUF fluid samples will be drawn following bypass. Ang-2, Ang-1, IL-8 and IL-10 levels will be measured to determine if present.	Upon MUF completion, on average 2 hours	No