Clinical trial NCT01656941: Genetic Determinants of Congenital Heart Disease Outcomes
Official title: The GECHO Trial: Genetic Determinants of Congenital Heart Disease Outcomes
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Congenital Heart Disease
Hypoplastic Left Heart Syndrome
Hypoplastic Right Heart Syndrome
d-Transposition of the Great Arteries
Keywords: neonate
congenital heart disease
single ventricle cardiac disease
hypoplastic left heart syndrome
hypoplastic right heart syndrome
d-Transposition of the Great Arteries
Lead sponsor: University of Michigan
Sponsor class: OTHER
Collaborators: name: Royal Children's Hospital
name: Medical University of South Carolina
name: Emory University
name: Medical College of Wisconsin
First posted: 2012-08-03
Enrollment: 250
Sex: ALL
Maximum age (years): 30
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Contribution of genetic variation in oxidative stress management to differences in short term outcomes after repair for severe cardiac disease in the neonatal period
timeFrame: Duration of initial perioperative hospitalization (~2-4 weeks)
Secondary outcomes:
measure: 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
timeFrame: Interval from hospital discharge following stage I surgical palliation until hospital admission for stage II surgical palliation (~4-6 months of age)
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Ann Arbor
country: United States
facility: C.S. Mott Children's Hospital, University of Michigan Health System
state: Michigan
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Melbourne
country: Australia
facility: The Royal Children's Hospial Melbourne
state: Victoria
Study officials:
affiliation: University of Michigan
name: Nicole S Wilder, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Michigan
name: Mark W Russell, MD
role: PRINCIPAL_INVESTIGATOR
References: