Comparison of Two Types of Shunts in Infants With Single Ventricle Defect Undergoing Staged Reconstruction--Pediatric Heart Network

Study Overview
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Brief Summary
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This trial will evaluate the efficacy and safety of the modified Blalock-Taussig shunt (MBTS) compared to the right ventricle to pulmonary artery (RV-to-PA) shunt; compare the effect of the MBTS to that of the RV-to-PA shunt on the incidence of death or cardiac transplantation at 12 months post randomization; and compare the effect of the two shunts on intensive care unit (ICU) morbidity, unintended cardiovascular interventional procedures, right ventricular function, tricuspid valve regurgitation, pulmonary artery growth, and neurodevelopmental outcome.

Detailed Description
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BACKGROUND: Hypoplastic left heart syndrome (HLHS) and related single right ventricle anomalies are the highest risk congenital cardiovascular malformations. Surgical repair begins with the Norwood procedure during the newborn period, a stage II procedure at 4 to 6 months of age, and Fontan procedure at 18 to 36 months. The Norwood procedure remains one of the highest risk procedures in congenital heart surgery. A few small nonrandomized studies of a novel approach to the Norwood procedure have reported improved outcomes. This new approach uses a RV-to-PA shunt to provide pulmonary blood flow rather than the standard MBTS. This multi-center, randomized clinical trial will evaluate early and intermediate-term outcomes for patients undergoing a Norwood procedure with either the RV-to-PA shunt or the MBTS. This study has been approved by the Institutional Review/Research Ethics Boards of all participating clinical centers: Hospital for Sick Children, Toronto, Canada Children's Hospital Boston, Boston, MA Columbia College of Physicians and Surgeons, New York, NY Children's Hospital of Philadelphia, Philadelphia, PA Duke University Medical Center, Durham, NC Brody School of Medicine at East Carolina University, Greenville, NC Wake Forest Baptist Medical Center, Winston Salem, NC Medical University of South Carolina, Charleston, SC Children's Hospital of Wisconsin, Milwaukee, WI University of Michigan, Ann Arbor, MI Cincinnati Children's Hospital Medical Center, Cincinnati, OH Children's Hospital of Los Angeles, Los Angeles, CA Egleston Children's Hospital, Emory University, Atlanta, GA Congenital Heart Institute of Florida, University of South Florida, St. Petersburg, FL Alfred I. duPont Hospital for Children, Wilmington, DE DESIGN NARRATIVE: This is a prospective, randomized clinical trial of the RV-to-PA shunt versus MBTS in patients undergoing a Norwood procedure.

Official Title
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Trial of Right Ventricular Versus Modified Blalock-Taussig Shunt in Infants With Single Ventricle Defect Undergoing Staged Reconstruction (A Trial Conducted by the Pediatric Heart Network)

Conditions
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Heart Defects, Congenital

Intervention / Treatment
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* Procedure: Blalock-Taussig pulmonary artery shunt
* Procedure: Right ventricular to pulmonary artery shunt


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of hypoplastic left heart syndrome or related single, morphologic right ventricle anomaly Planned Norwood procedure Informed consent of parent(s) or legal guardian Exclusion Criteria: Single, morphologic left ventricle anomaly Preoperative identification of anatomy rendering either an MBTS or an RV-to-PA shunt technically impossible Any major congenital abnormality (i.e., congenital diaphragmatic hernia, tracheoesophageal fistula) or acquired extra-cardiac disorder (e.g., meconium aspiration with need for high frequency ventilation, persistent renal failure requiring dialysis) that, in the opinion of the investigator, could independently affect the likelihood of the subject meeting the primary endpoint
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: MBTS<br>Blalock-Taussig pulmonary artery shunt | Procedure: Blalock-Taussig pulmonary artery shunt<br>* Performed at stage I palliative surgery for babies born with HLHS<br>* Other names: MBTS procedure;|
| Active Comparator: RVPAS<br>Right ventricular to pulmonary artery shunt | Procedure: Right ventricular to pulmonary artery shunt<br>* Performed at stage I palliative surgery for babies born with HLHS<br>* Other names: RV to PA or Sano procedure;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients Who Died or Received a Heart Transplant | The primary outcome was the proportion of patients who died or had cardiac transplantation 12 months after randomization. | Measured at 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Deaths or Heart Transplants Over Time From Randomization to the End of the Trial | This secondary outcome was the proportion of deaths or cardiac transplantation over time from randomization to the end of the trial. | From Randomization to the End of the Trial, an average of 32 months | 
| Echocardiographic Measures of Heart Size and Function: Right Ventricle (RV) End-diastolic Volume Indexed to Body Surface Area (BSA) | Right ventricular end-diastolic volume indexed to BSA^1.3. Echocardiograms were performed at time points relative to the two palliative surgeries (post-Norwood and pre-Stage II) as well as at the specific time point of 14 months of age. | Measured post-Norwood, an average of 17 days post-Norwood | 
| Echocardiographic Measures of Heart Size and Function: RV End-diastolic Volume Indexed to BSA | Right ventricular end-diastolic volume indexed to BSA^1.3. Echocardiograms were performed at time points relative to the two palliative surgeries (post-Norwood and pre-Stage II) as well as at the specific time point of 14 months of age. | Measured pre-stage II surgery, an average of 15 days pre-stage II surgery | 
| Echocardiographic Measures of Heart Size and Function: RV End-diastolic Volume Indexed to BSA | Right ventricular end-diastolic volume indexed to BSA^1.3. Echocardiograms were performed at time points relative to the two palliative surgeries (post-Norwood and pre-Stage II) as well as at the specific time point of 14 months of age. | Measured at 14 months of age | 
| Echocardiographic Measures of Heart Size and Function: RV End-systolic Volume Indexed to BSA | Right ventricular end-systolic volume indexed to BSA. Echocardiograms were performed at time points relative to the two palliative surgeries (post-Norwood and pre-Stage II) as well as at the specific time point of 14 months of age. | Measured post-Norwood, an average of 17 days post-Norwood | 
| Echocardiographic Measures of Heart Size and Function: RV End-systolic Volume Indexed to BSA | Right ventricular end-systolic volume indexed to BSA^1.3. Echocardiograms were performed at time points relative to the two palliative surgeries (post-Norwood and pre-Stage II) as well as at the specific time point of 14 months of age. | Measured pre-stage II surgery, an average of 15 days pre-stage II surgery | 
| Echocardiographic Measures of Heart Size and Function: RV End-systolic Volume Indexed to BSA | Right ventricular end-systolic volume indexed to BSA^1.3. Echocardiograms were performed at time points relative to the two palliative surgeries (post-Norwood and pre-Stage II) as well as at the specific time point of 14 months of age. | Measured at 14 months of age | 
| Echocardiographic Measures of Heart Size and Function: RV Ejection Fraction | Right ventricular ejection fraction: 100 x (RV end-diastolic volume - RV end-systolic volume)/RV end-diastolic volume. Echocardiograms were performed at time points relative to the two palliative surgeries (post-Norwood and pre-Stage II) as well as at the specific time point of 14 months of age. | Measured post-Norwood, an average of 17 days post-Norwood | 
| Echocardiographic Measures of Heart Size and Function: RV Ejection Fraction | Right ventricular ejection fraction: 100 x (RV end-diastolic volume - RV end-systolic volume)/RV end-diastolic volume. Echocardiograms were performed at time points relative to the two palliative surgeries (post-Norwood and pre-Stage II) as well as at the specific time point of 14 months of age. | Measured pre-stage II surgery, an average of 15 days pre-stage II surgery | 
| Echocardiographic Measures of Heart Size and Function: RV Ejection Fraction | Right ventricular ejection fraction: 100 x (RV end-diastolic volume - RV end-systolic volume)/RV end-diastolic volume. Echocardiograms were performed at time points relative to the two palliative surgeries (post-Norwood and pre-Stage II) as well as at the specific time point of 14 months of age. | Measured at 14 months of age | 
| Angiographic Findings: Left Pulmonary Artery Size | Diameter of distal left pulmonary artery. Angiograms were performed at the time points relative to the second palliative surgery (pre-Stage II). | Measured pre-stage II surgery, on average 26 days prior to stage II palliation | 
| Angiographic Findings: Right Pulmonary Artery Size | Diameter of distal right pulmonary artery. Angiograms were performed at the time points relative to the second palliative surgery (pre-Stage II). | Measured pre-stage II surgery, on average 26 days prior to stage II palliation | 
| Unintended Cardiovascular Interventional Procedures | Unintended cardiovascular procedures included balloon dilation of the shunt or branch pulmonary arteries, stent placement in the shunt or branch pulmonary arteries, shunt revision, crossover between MBTS and RVPAS shunt, balloon dilation, stent placement or surgical revisions of the neo-aorta, and pulmonary artery reconstructions, other than those undertaken as a standard component of the stage II procedure. The number of cardiovascular procedures was analyzed; trial participants may have had more than one unintended cardiovascular. procedure. | From Randomization to 12 months | 
| Complications: Total Number Experienced During Norwood Hospitalization | Complications, reported as 'Other Adverse Events' in the safety section, are those adverse events that were not considered serious. Many normal peri-operative occurrences meet the standard criteria of an adverse event; therefore, for this trial a serious adverse event was (a) death, (b) acute shunt failure requiring intervention, (c) cardiac arrest requiring CPR and medications, (d) cardiopulmonary insufficiency requiring ECMO, (e) cardiovascular re-operation (unplanned), (f) necrotizing enterocolitis requiring laparotomy, and (g) any event considered by the study investigator as serious. | Norwood Hospitalization, an average of 36 days | 
| Complications: Total Number Experienced From Norwood Discharge to Stage II Discharge | Complications, reported as 'Other Adverse Events' in the safety section, are those adverse events that were not considered serious. Many normal peri-operative occurrences meet the standard criteria of an adverse event; therefore, for this trial a serious adverse event was (a) death, (b) acute shunt failure requiring intervention, (c) cardiac arrest requiring CPR and medications, (d) cardiopulmonary insufficiency requiring ECMO, (e) cardiovascular re-operation (unplanned), (f) necrotizing enterocolitis requiring laparotomy, and (g) any event considered by the study investigator as serious. | From Norwood Discharge to Stage II discharge, an average of 4.2 months | 
| Complications: Total Number Experienced From Stage II Discharge to 14 Months of Age | Complications, reported as 'Other Adverse Events' in the safety section, are those adverse events that were not considered serious. Many normal peri-operative occurrences meet the standard criteria of an adverse event; therefore, for this trial a serious adverse event was (a) death, (b) acute shunt failure requiring intervention, (c) cardiac arrest requiring CPR and medications, (d) cardiopulmonary insufficiency requiring ECMO, (e) cardiovascular re-operation (unplanned), (f) necrotizing enterocolitis requiring laparotomy, and (g) any event considered by the study investigator as serious. | From Stage II Discharge to 14 Months of Age, an average of 8.9 months |