Genetic Determinants of Congenital Heart Disease Outcomes (GECHO)

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by University of Michigan
Sponsor:
Collaborators:
Royal Children's Hospital
Medical University of South Carolina
Emory University
Medical College of Wisconsin
Information provided by (Responsible Party):
Nicole S. Wilder, University of Michigan
ClinicalTrials.gov Identifier:
NCT01656941
First received: July 19, 2012
Last updated: December 9, 2013
Last verified: December 2013
  Purpose

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.


Condition
Severe Congenital Heart Disease
Hypoplastic Left Heart Syndrome
Hypoplastic Right Heart Syndrome
dTGA

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: The GECHO Trial: Genetic Determinants of Congenital Heart Disease Outcomes

Resource links provided by NLM:


Further study details as provided by University of Michigan:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]

    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 Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]

    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).


Biospecimen Retention:   Samples With DNA

Whole blood samples will be frozen and stored until DNA can be isolated. Eventually, isolated DNA samples will be frozen and stored in a biorepository.


Estimated Enrollment: 800
Study Start Date: March 2011
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
Groups/Cohorts
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

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

Ages Eligible for Study:   up to 30 Days
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

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
  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: NCT01656941

Contacts
Contact: Constance Burke, RN 734-936-0734 cnburke@umich.edu
Contact: Nicole S Wilder, MD 734-936-1016 nicowild@umich.edu

Locations
United States, Georgia
Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: William Mahle, MD    404-256-2593    wmahle@emory.edu   
Principal Investigator: William Mahle, MD         
United States, Michigan
C.S. Mott Children's Hospital, University of Michigan Health System Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Constance Burke, RN    734-936-0734    cnburke@umich.edu   
Principal Investigator: Nicole S Wilder, MD         
Principal Investigator: Mark W Russell, MD         
United States, South Carolina
Medical University of South Carolina Recruiting
Charleston, South Carolina, United States, 29403
Contact: Andrew Atz, MD    843-792-2945    atzam@musc.edu   
Contact: Patricia Infinger    843-792-7857    infingep@musc.edu   
Principal Investigator: Andrew Atz, MD         
United States, Wisconsin
Medical College of Wisconsin Active, not recruiting
Milwaukee, Wisconsin, United States, 53226
Australia, Victoria
The Royal Children's Hospial Melbourne Recruiting
Melbourne, Victoria, Australia, 3052
Contact: Michael Clifford, MD    0393455522    michael.clifford@rch.org.au   
Contact: Suzette Sheppard       suzette.sheppard@mcri.edu.au   
Principal Investigator: Michael Clifford, MD         
Sponsors and Collaborators
University of Michigan
Royal Children's Hospital
Medical University of South Carolina
Emory University
Medical College of Wisconsin
Investigators
Principal Investigator: Nicole S Wilder, MD University of Michigan
Principal Investigator: Mark W Russell, MD University of Michigan
  More Information

No publications provided

Responsible Party: Nicole S. Wilder, Clinical Assistant Professor, University of Michigan
ClinicalTrials.gov Identifier: NCT01656941     History of Changes
Other Study ID Numbers: GECHO
Study First Received: July 19, 2012
Last Updated: December 9, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Michigan:
neonate
congenital heart disease
single ventricle cardiac disease
hypoplastic left heart syndrome
hypoplastic right heart syndrome
dTGA

Additional relevant MeSH terms:
Heart Diseases
Syndrome
Heart Defects, Congenital
Hypoplastic Left Heart Syndrome
Cardiovascular Diseases
Disease
Pathologic Processes
Cardiovascular Abnormalities
Congenital Abnormalities

ClinicalTrials.gov processed this record on October 16, 2014