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

Heart Defects, Congenital Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00115934
• Other study ID #: 194
• Secondary ID: U01HL068270U01HL
• Status: Completed
• Phase: Phase 3
• First received: June 26, 2005
• Last updated: August 2, 2013
• Start date: May 2005
• Est. completion date: October 2009

Study information

• Verified date: August 2013
• Source: New England Research Institutes
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 555
• Est. completion date: October 2009
• Est. primary completion date: September 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Congenital Abnormalities
• Heart Defects, Congenital

Intervention

Procedure:
• Blalock-Taussig pulmonary artery shunt
Performed at stage I palliative surgery for babies born with HLHS
• Right ventricular to pulmonary artery shunt
Performed at stage I palliative surgery for babies born with HLHS

Locations

Country	Name	City	State
Canada	Hospital for Sick Children	Toronto	Ontario
United States	University of Michigan Health System/Mott Hospital	Ann Arbor	Michigan
United States	Children's Healthcare of Atlanta at Egleston	Atlanta	Georgia
United States	Children's Hospital Boston	Boston	Massachusetts
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Duke University Medical Center	Durham	North Carolina
United States	Children's Hospital of Los Angeles	Los Angeles	California
United States	Children's Hospital of Wisconsin	Milwaukee	Wisconsin
United States	Columbia College of Physicians and Surgeons	New York	New York
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Cardiac Surgical Associates	St. Petersburg	Florida
United States	Alfred I. duPont Hospital for Children	Wilmington	Delaware

Sponsors (3)

Lead Sponsor	Collaborator
New England Research Institutes	National Heart, Lung, and Blood Institute (NHLBI), Pediatric Heart Network

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (6)

Atz AM, Travison TG, Williams IA, Pearson GD, Laussen PC, Mahle WT, Cook AL, Kirsh JA, Sklansky M, Khaikin S, Goldberg C, Frommelt M, Krawczeski C, Puchalski MD, Jacobs JP, Baffa JM, Rychik J, Ohye RG; Pediatric Heart Network Investigators. Prenatal diagn — View Citation

Johnson JN, Ansong AK, Li JS, Xu M, Gorentz J, Hehir DA, del Castillo SL, Lai WW, Uzark K, Pasquali SK. Celiac artery flow pattern in infants with single right ventricle following the Norwood procedure with a modified Blalock-Taussig or right ventricle to — View Citation

Ohye RG, Devaney EJ, Hirsch JC, Bove EL. The modified Blalock-Taussig shunt versus the right ventricle-to-pulmonary artery conduit for the Norwood procedure. Pediatr Cardiol. 2007 Mar-Apr;28(2):122-5. Epub 2007 Feb 16. Review. — View Citation

Ohye RG, Gaynor JW, Ghanayem NS, Goldberg CS, Laussen PC, Frommelt PC, Newburger JW, Pearson GD, Tabbutt S, Wernovsky G, Wruck LM, Atz AM, Colan SD, Jaggers J, McCrindle BW, Prakash A, Puchalski MD, Sleeper LA, Stylianou MP, Mahony L; Pediatric Heart Network Investigators. Design and rationale of a randomized trial comparing the Blalock-Taussig and right ventricle-pulmonary artery shunts in the Norwood procedure. J Thorac Cardiovasc Surg. 2008 Oct;136(4):968-75. doi: 10.1016/j.jtcvs.2008.01.013. Epub 2008 May 19. — View Citation

Ohye RG, Sleeper LA, Mahony L, Newburger JW, Pearson GD, Lu M, Goldberg CS, Tabbutt S, Frommelt PC, Ghanayem NS, Laussen PC, Rhodes JF, Lewis AB, Mital S, Ravishankar C, Williams IA, Dunbar-Masterson C, Atz AM, Colan S, Minich LL, Pizarro C, Kanter KR, Ja — View Citation

Virzi L, Pemberton V, Ohye RG, Tabbutt S, Lu M, Atz TC, Barnard T, Dunbar-Masterson C, Ghanayem NS, Jacobs JP, Lambert LM, Lewis A, Pike N, Pizarro C, Radojewski E, Teitel D, Xu M, Pearson GD. Reporting adverse events in a surgical trial for complex conge — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes