Hybrid Versus Norwood Management Strategies in Infants Undergoing Single Ventricle Palliation

The Influence of Postoperative Systemic Oxygen Transport on Neurologic and Functional Outcomes in Infants Undergoing Single Ventricle Palliation With Norwood and Hybrid Management Strategies

The purpose of this trial is to determine, at 3 years of life, how the neurologic and functional outcomes in infants with single ventricles are different when comparing children treated with the Hybrid strategy to the Norwood strategy.

Study Overview

• Status: Unknown
• Conditions: Congenital Heart Disease
• Intervention / Treatment: Procedure: Hybrid Strategy; Procedure: Norwood management strategy

Detailed Description

Neurologic deficits in children with single ventricle physiology are believed to be associated with the reconstruction of the aortic arch during the initial Norwood procedure as a neonate. In the last few years, a new management strategy (the 'Hybrid' strategy) has been proposed which defers the aortic arch reconstruction to a second stage procedure at 4-6 months of age.

Proponents of the Hybrid strategy assert that the avoidance of cardiopulmonary bypass and circulatory arrest in the neonatal period will avoid neurologic injury in the critical neonatal period and thereby result in superior long-term neurologic outcomes.

We are testing whether the Hybrid management strategy is associated with superior neurologic outcomes or not.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada
      • Recruiting
      • The Hospital for Sick Children
      • Contact: Christopher Caldarone; Phone Number: 416-813-6420; Email: christopher.caldarone@sickkids.ca
      • Contact: Glen VanArsdell; Phone Number: 416-813-6420; Email: glen.vanarsdell@sickkids.ca
      • Principal Investigator: Christopher Caldarone, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 3 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Diagnosis of functional single ventricle anatomy amenable to Norwood or Hybrid first stage palliation.
2. Informed consent of parent(s) or legal guardian.

Exclusion Criteria:

1. Pre-operative identification of anatomy rendering either a Norwood or Hybrid procedure clinically inappropriate;
2. Recent history of significant cerebral bleed or necrotizing enterocolitis;
3. Severe hemodynamic instability;
4. Any other major congenital abnormality (i.e. congenital diaphragmatic hernia, tracheoesophageal fistula) or clinically significant acquired extra-cardiac disorder (e.g. meconium aspiration with need for high frequency ventilation, persistent renal failure requiring dialysis).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm 1; Hybrid Management	Procedure: Hybrid Strategy; Hybrid palliation will be performed as per current clinical practice at The Hospital for Sick Children. The 'Hybrid' management strategy utilizes catheter-based and non-open heart surgical procedures in the neonatal period to stabilize the neonate.10 The majority of the reconstruction is thereby deferred to 4-6 months of age, at which time the second stage procedure including an aortic arch reconstruction is performed. The third stage procedure (Fontan) is identical between Norwood and Hybrid strategies.
Active Comparator: Arm 2; Norwood Management	Procedure: Norwood management strategy; Norwood palliation will be performed as per current clinical practice at The Hospital for Sick Children.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurologic and functional outcomes	Neurodevelopmental and functional status will be assessed at 14 months of age using the Bayley Scales of Infant Development®-Third Edition (BSID-III), MacArthur Commmunicative Development Inventory/Words and Gestures (CDI) and Functional Status-II-Revised Questionnaire.	14 months of age
Neurologic and functional outcomes	At ~3 years of age, the Vineland Scale,the Mullen Developmental Scale, and the BASC behavioural scale will be formally assessed	3 years of age (during procedure 3 pre-op)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemodynamic Assessment	Arterial, superior vena cava and pulmonary vein pressure will be monitored via indwelling catheters. This measurement will be taken during: procedure 1 pre-op, procedure 1 post-op, procedure 2 pre-op, and procedure 2 post-op.	Baseline and 4-6 months
Blood Sampling	Standard blood gas samples will be drawn from indwelling arterial, SVC and pulmonary vein catheters to provide oxygen saturation and lactate data. This measurement will be taken immediately after chest opening, and then postoperatively at 2 hour intervals during the first 24 hours and at 4 hour intervals during the following 48 hours after first and second stage procedures.	Baseline and 4-6 months
Systemic Oxygen Consumption	Measurement of pre- and post-operative VO2. This measurement will be taken during: procedure 1 pre-op, procedure 1 post-op, and procedure 2 pre-op	Baseline and 4-6 months
Cerebral Oxygen Transport Surrogate Measurements	Cerebral oxygen saturation (ScO2) will be continuously measured by Near Infrared Spectroscopy (NIRS). This measurement will be taken during: procedure 1 pre-op, procedure 1 post-op, procedure 2 pre-op, and procedure 2 post-op.	Baseline and 4-6 months
Cerebral Blood Flow Velocity	Transcranial Doppler sonography using the TCD through the middle cerebral artery with a 2 MHz pulse-wave ultrasound transducer will be used to measure cerebral blood flow velocity non-invasively. This measurement will be taken during: procedure 1 pre-op, procedure 1 post-op, procedure 2 pre-op, and procedure 2 post-op.	Baseline and 4-6 months
Electroencephalograph	Locked digital video electroencephalography (DVEEG) will be used to continuously monitor ischemic injury and seizures. This will be done at the folling times: procedure 1 pre-op, procedure 1 post-op prior to discharge, and procedure 2 post-op.	Baseline and 4-6 months
MRI scans	Brain imaging will be assessed for evidence of congenital malformations or structural abnormalities, cerebral edema, acute ischemia, intracranial hemorrhages, periventricular leukomalacia (PVL), focal tissue loss, atrophy, delays in myelin maturation and infarcts. The MRI will be done during procedure 1 post-op prior to discharge, procedure 2 post-op prior to discharge and procedure 3 pre-op.	Baseline, 4-6 months and 2-3 years

Collaborators and Investigators

• Sponsor: The Hospital for Sick Children
• Investigators: Principal Investigator: Christopher Caldarone, The Hospital for Sick Children, Toronto Canada

Publications and helpful links

Helpful Links

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Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Anticipated): March 1, 2012
• Study Completion (Anticipated): March 1, 2012

Study Registration Dates

• First Submitted: March 23, 2010
• First Submitted That Met QC Criteria: May 27, 2010
• First Posted (Estimate): May 31, 2010

Study Record Updates

• Last Update Posted (Estimate): May 31, 2010
• Last Update Submitted That Met QC Criteria: May 27, 2010
• Last Verified: May 1, 2010

More Information

Terms related to this study

• Keywords: congenital heart disease; Hybrid; Norwood; single ventricle
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Diseases; Heart Defects, Congenital; Univentricular Heart
• Other Study ID Numbers: 1000013962