Plasma Angiopoietin Levels in Children Following Cardiopulmonary Bypass

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Yale University
ClinicalTrials.gov Identifier:
NCT01489475
First received: November 29, 2011
Last updated: October 4, 2013
Last verified: October 2013
  Purpose

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.


Condition
Congenital Heart Defects

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Plasma Angiopoietin Levels in Children Undergoing Modified Ultrafiltration Following Cardiopulmonary Bypass

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • Change from baseline in pro- and anti-inflammatory protein levels after modified ultrafiltration [ Time Frame: baseline to completion of MUF, on average 2 hours ] [ Designated as safety issue: No ]
    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.

  • Change from baseline in pro- and anti-inflammatory protein levels at ICU admission [ Time Frame: baseline to ICU admission, on average 7 hours ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Biomarker correlation with patient outcome [ Time Frame: Duration of pediatric ICU admission, on average 7 days ] [ Designated as safety issue: No ]
    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.

  • Pro- and anti-inflammatory protein presence in ultrafiltration fluid [ Time Frame: Upon MUF completion, on average 2 hours ] [ Designated as safety issue: No ]
    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.


Biospecimen Retention:   Samples With DNA
  1. Modified ultrafiltration fluid
  2. Whole blood which will be spun down to plasma (cells to be discarded)

Enrollment: 31
Study Start Date: November 2011
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Detailed 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.

  Eligibility

Ages Eligible for Study:   up to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients with congenital heart disease, undergoing surgical intervention requiring cardiopulmonary bypass and modified ultrafiltration will be recruited.

Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01489475

Locations
United States, Connecticut
Yale Children's Hospital
New Haven, Connecticut, United States, 06520
Sponsors and Collaborators
Yale University
Investigators
Study Director: John S Giuliano, Jr, MD Yale University
  More Information

No publications provided

Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT01489475     History of Changes
Other Study ID Numbers: 1107008778
Study First Received: November 29, 2011
Last Updated: October 4, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Yale University:
children
congenital heart defects
cardiopulmonary bypass
modified ultrafiltration
angiopoietins
cytokines

Additional relevant MeSH terms:
Heart Defects, Congenital
Cardiovascular Abnormalities
Cardiovascular Diseases
Heart Diseases
Congenital Abnormalities

ClinicalTrials.gov processed this record on July 23, 2014