Genetic Determinants of Congenital Heart Disease Outcomes (GECHO)

The GECHO Trial: Genetic Determinants of Congenital Heart Disease Outcomes

The purpose of this study is to examine the role of genetic variation in the oxidative stress response on critical perioperative and short-term outcomes after neonatal heart surgery. The goals will be to determine 1) if the oxidative stress pathway is an important one for therapeutic intervention in neonates with severe congenital heart defects and 2) if variants in the oxidative response pathway can be used to identify patients at increased risk for adverse outcomes.

Study Overview

• Status: Completed
• Conditions: Congenital Heart Disease; Hypoplastic Left Heart Syndrome; Hypoplastic Right Heart Syndrome; d-Transposition of the Great Arteries

Detailed Description

For physicians caring for children with congenital cardiac defects, perhaps the greatest challenge is to improve the survival and functional outcomes of patients with severe defects requiring surgical repair or palliation in the first month of life. These cardiac defects can be associated with 5 year mortality rates of up to 30% with significant disabilities in many of the survivors. As with every medical condition, patient outcomes depend on the complex interaction of the disease process, the medical and surgical interventions to treat the disease, and the inherent capacity of the patient to respond to both the disease and its treatment.

For patients with severe cardiac defects, the greatest risk for morbidity and mortality occurs during and shortly after their neonatal surgical repair. During surgery to repair severe cardiac defects, the body is cooled and the heart is stopped. In many cases, blood flow to the vital organs is interrupted or restricted for a significant period of time while the aortic arch is reconstructed. This process places profound stress on the patient's capacity to tolerate these insults without sustaining irreversible injury to tissues such as the heart, brain, and kidneys. That there is such a wide range of outcomes after this surgery, even between patients with similar clinical features, suggests that there are important individual differences in patients' abilities to respond to this stress that is determined by differences in their genetic traits.

The importance of the interaction between the controlled trauma of the surgical environment and a patient's genetic background in determining patient outcomes has led to the new discipline of "peri-operative genomics." In this study, we will examine the contribution of gene-environment interactions to perioperative and short-term outcomes in neonates with severe congenital cardiac defects.

• Study Type: Observational
• Enrollment (Actual): 250

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3052
      • The Royal Children's Hospial Melbourne
• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • C.S. Mott Children's Hospital, University of Michigan Health System
  • South Carolina
    • Charleston, South Carolina, United States, 29403
      • Medical University of South Carolina
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College Of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 1 month (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Neonates with d-transposition of the great arteries undergoing the arterial switch procedure and neonates with single ventricle cardiac disease undergoing stage I surgical palliation at the University of Michigan or other collaborating institutions.

Description

Inclusion Criteria:

• d-transposition of the great arteries or single ventricle cardiac disease
• Less than or equal to 30 days of age
• Planned arterial switch operation or stage I surgical palliation (Norwood)with aortic arch reconstruction

Exclusion Criteria:

• Known trisomy 13, 18, or 21
• Any major non-cardiac anomaly that precludes the patient from cardiac surgery

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
d-Transposition of the Great Arteries; Neonates with d-transposition of the great arteries (dTGA) undergoing the arterial switch operation with cardiopulmonary bypass
Single ventricle cardiac disease; Neonates with single ventricle cardiac disease (SVCD) undergoing stage I surgical palliation (Norwood) with cardiopulmonary bypass

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Contribution of genetic variation in oxidative stress management to differences in short term outcomes after repair for severe cardiac disease in the neonatal period	Genotyping will be performed on 10 variants in the oxidative stress response pathway and we will combine risk genotypes in order to evaluate the cumulative effect of both detrimental and beneficial alleles on post-operative outcomes. Composite short term outcome measure includes: ICU length of stay (days) Time to initial extubation (hours) Cardiac arrest or ECMO support (Y/N) Delayed sternal closure (Y/N) Serious adverse event (Y/N) Greater than 1 serious adverse event (Y/N)	Duration of initial perioperative hospitalization (~2-4 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Contribution of genetic variation in oxidative stress management to differences in interstage mortality and pre-Stage II cardiovascular function in patients with single ventricle cardiac disease	Composite outcome; Growth parameters (height, weight, head circumference); AV valve insufficiency (By echocardiogram and cardiac catheterization) , Ventricular function (ejection fraction by echocardiogram and by cardiac catheterization), Central venous pressure and ventricular end diastolic pressure (by catheterization), Interstage Death (Y/N).	Interval from hospital discharge following stage I surgical palliation until hospital admission for stage II surgical palliation (~4-6 months of age)

Collaborators and Investigators

• Sponsor: University of Michigan
• Collaborators: Medical University of South Carolina; Emory University; Medical College of Wisconsin; Royal Children's Hospital
• Investigators: Principal Investigator: Nicole S Wilder, MD, University of Michigan; Principal Investigator: Mark W Russell, MD, University of Michigan

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (ACTUAL): March 16, 2017
• Study Completion (ACTUAL): March 16, 2017

Study Registration Dates

• First Submitted: July 19, 2012
• First Submitted That Met QC Criteria: July 31, 2012
• First Posted (ESTIMATE): August 3, 2012

Study Record Updates

• Last Update Posted (ACTUAL): August 10, 2021
• Last Update Submitted That Met QC Criteria: August 3, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: neonate; congenital heart disease; hypoplastic left heart syndrome; single ventricle cardiac disease; hypoplastic right heart syndrome; d-Transposition of the Great Arteries
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Disease; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Diseases; Syndrome; Heart Defects, Congenital; Hypoplastic Left Heart Syndrome; Transposition of Great Vessels
• Other Study ID Numbers: GECHO