Prognostic Markers of Inflammation in Infants Undergoing Cardiopulmonary Bypass (ProCard)

Prognostic Markers of Inflammation in Infants Undergoing Cardiopulmonary Bypass (ProCard): an Observational Pilot Study

This study evaluates the effect of heart-lung bypass on babies undergoing cardiac surgery. The investigators want to learn more about the inflammation that exposure to bypass creates in the body by studying markers of inflammation and cell injury in the bloodstream. Additionally, the investigators want to examine if these markers can predict which babies develop post-surgical complications. The hypothesis is that babies who undergo bypass will have higher levels of these markers than babies not exposed to bypass and that these markers will correlate with how the baby does clinically after surgery.

This study will evaluate markers via blood sampling in babies with congenital heart disease who do not undergo cardiac surgery, those that undergo surgery without bypass, and those that undergo surgery with bypass. The overall goal is that this study will lead to useful biomarkers and lay the groundwork for future novel therapies aimed at improving outcomes for babies who require heart-lung bypass.

Study Overview

• Status: Completed
• Conditions: Inflammation; Inflammatory Response; Cardiopulmonary Bypass; Congenital Heart Defect; Low Cardiac Output Syndrome
• Intervention / Treatment: Procedure: Single blood draw; Procedure: Multiple blood draws; Procedure: Multiple blood draws

Detailed Description

This is a minimal risk observational study looking at markers of inflammation and cell injury in the bloodstream of babies with congenital heart disease, with a particular emphasis on whether these markers can predict low cardiac output syndrome in infants who undergo heart-lung bypass. Low cardiac output syndrome is a common postoperative complication marked by poor blood flow to the body affecting nearly 1/3 of infants post-bypass and is associated with significant morbidity and mortality.

Babies not requiring surgery will serve as the control group. Infants in group 1 will have 0.5 ml of blood drawn prior to discharge. This will be scavenged from the laboratory when possible. Infants in groups 2 and 3 will require serial blood draws over peri-operative time points each in the volume of 0.5 ml.

Group 2:

T0 = Before surgery (in the OR) T1 = After chest closure or end of case (in the OR) T2 = On admission to the pediatric intensive care unit T3 = Timed 4-6 hours after the time of admission T4 = Timed 12 hours (+/- 1 hour) after the time of admission T5 = Timed 24 hours (+/-1 hour) after the time of admission

Group 3:

T0 =Pre-cardiopulmonary bypass to be obtained in the operating room just prior to surgery T1 = After going on bypass (but prior to modified ultrafiltration) T2 = After modified ultrafiltration T3 = On admission to the pediatric intensive care unit T4 = Timed 4-6 hours after the time of admission T5 = Timed 12 hours (+/- 1 hour) after the time of admission T6 = Timed 24 hours (+/-1 hour) after the time of admission

• Study Type: Observational
• Enrollment (Actual): 38

Contacts and Locations

Study Locations

• United States
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73117
      • University of Oklahoma Health Sciences Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 6 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Infants <6 months of age with congenital heart disease at OU Children's Hospital

Description

Inclusion Criteria:

• Infants < 6 months of age
• Born at ≥ 36 weeks gestational age
• Birth weight ≥ 2.5 kilograms
• Postnatally confirmed congenital heart disease by echocardiogram

Exclusion Criteria:

• Requiring ≥ 2 vasopressors prior to surgery
• Preoperative proven sepsis within one week of surgery
• Prior surgery within one week of cardiac repair (except PA banding which is not excluded)
• Cardiac catheterization within one week of surgery
• Significant extra-cardiac anomalies that may impair organ function

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Control/Nonsurgical; Infants with postnatally confirmed acyanotic congenital heart disease not expected to require surgery in the first six months of life.	Procedure: Single blood draw; One blood draw of 0.5 ml volume prior to discharge
Surgery w/o bypass; Infants with postnatally confirmed congenital heart disease requiring cardiac surgery without cardiopulmonary bypass.	Procedure: Multiple blood draws; Blood draw at 6 peri-operative time points.; Procedure: Multiple blood draws; Blood draw at 7 peri-operative time points
Surgery w/ bypass; Infants with postnatally confirmed congenital heart disease requiring cardiac surgery with cardiopulmonary bypass.	Procedure: Multiple blood draws; Blood draw at 6 peri-operative time points.; Procedure: Multiple blood draws; Blood draw at 7 peri-operative time points

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarker levels and their relationship to LCOS	Changes in markers of inflammation and cell injury (histones, IL-6, etc.) and correlation with patients who develop low cardiac output syndrome	Baseline level and described time points over the first twenty-four hours postoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in level of inflammatory response	Changes in markers of inflammation and cell injury (IL-6, IL-8, etc.) in the peri-operative period (prior to surgery up to 24 hours postop)	Baseline, up to 24 hours
Length of mechanical ventilation	Number of days on mechanical ventilation following day of surgery until the point of extubation	Participants will be followed throughout hospital course, maximum length of follow-up one year
Acute kidney injury	Doubling of creatinine in first twenty four hours compared to preoperative levels	Participants will be followed for the first twenty four hours postoperatively
Extracorporeal membrane oxygenation (ECMO)	Whether or not patient requires ECMO cannulation	First 48 hours postoperatively
ICU length of stay	Number of days requiring pediatric/cardiac intensive care unit following day of surgery	Participants will be followed throughout PICU/CVICU stay, maximum length of follow-up one year
Hospital length of stay	Number of hospital days patient requires following the day of surgery	Participants will be followed throughout entire hospital course, maximum length of follow-up one year
Mortality risk	Pediatric risk of mortality-3 scale (PRISM-3) and pediatric index of mortality (PIM-2)	PIM-2 calculated within one hour of admission to PICU and PRISM-3 calculated at 12 and 24 hours after PICU admission
Mortality	Any type of death that occurs during patient's hospitalization	Participants will be followed throughout hospital course, maximum length of follow-up one year
Low cardiac output syndrome	At least two of the following criteria at any post-operative time point within the first twenty four hours: (a) prolonged cap refill >3 sec, SBP <5th %ile for age and gender, low UOP <1 cc/kg/hr for at least 6 hr not responsive to diuretics, persistently elevated arterial lactate >2 and metabolic acidosis defined as an increase in the base deficit of >4, inotropic score >20, cardiac arrest within 48 hr after surgery, or the need for extracorporeal membrane oxygenation (ECMO) for hemodynamic instability within 48 hours postop	Assessed at 48 hours postoperatively

Collaborators and Investigators

• Sponsor: University of Oklahoma
• Investigators: Principal Investigator: Hala Chaaban, MD, University of Oklahoma

Study record dates

Study Major Dates

• Study Start (Actual): June 4, 2017
• Primary Completion (Actual): April 15, 2019
• Study Completion (Actual): April 15, 2019

Study Registration Dates

• First Submitted: March 13, 2017
• First Submitted That Met QC Criteria: May 3, 2017
• First Posted (Actual): May 8, 2017

Study Record Updates

• Last Update Posted (Actual): April 30, 2019
• Last Update Submitted That Met QC Criteria: April 26, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Inflammation; Heart Defects, Congenital; Cardiac Output, Low
• Other Study ID Numbers: 7676

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No