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.

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Key information

Conditions

Congenital Heart Disease Cardiovascular Abnormalities Cardiovascular Diseases Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Heart Defects, Congenital Heart Diseases Hypoplastic Left Heart Syndrome Hypoplastic Right Heart Syndrome d-Transposition of the Great Arteries

Age range

Up to 30 day

Sex eligibility

All sexes

Study type

Observational

Primary location

The Royal Children's Hospial Melbourne, Melbourne, Victoria, Australia

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Primary outcomes

Contribution of genetic variation in oxidative stress management to differences in short term outcomes after repair for severe cardiac disease in the neonatal period

Time frame: Duration of initial perioperative hospitalization (~2-4 weeks)

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)

Secondary outcomes

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

Time frame: Interval from hospital discharge following stage I surgical palliation until hospital admission for stage II surgical palliation (~4-6 months of age)
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).

Sponsors and collaborators

Lead sponsor

University of Michigan

Other

Collaborators

Emory University
Medical College of Wisconsin
Medical University of South Carolina
Royal Children's Hospital

Registry information

Official study title

The GECHO Trial: Genetic Determinants of Congenital Heart Disease Outcomes

Acronym: GECHO

Important dates

Study start: 2011
Primary completion: 2017
Study completion: 2017
First posted: Aug 3, 2012
Registry last updated: Aug 10, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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