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Pediatric REPlAcement of the PulmonaRy ValvE in Tetralogy of Fallot - (TOFandPVR)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03634072
Recruitment Status : Terminated (Unable to meet enrollment goal)
First Posted : August 16, 2018
Last Update Posted : September 17, 2021
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Children's Hospital of Philadelphia

Brief Summary:
Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart defect with the vast majority of survivors of corrective surgery left with some degree of right ventricular (RV) volume overload due to pulmonary regurgitation (PR) which cause RV enlargement with right heart failure, diminished biventricular function, ventricular arrhythmia, sudden death and decreased exercise performance over time. Pulmonary valve replacement has been thought to ameliorate these complications but the timing of replacement has yet to be determined with equipoise at the moment in this decision making process. As nearly all studies in this regard are retrospective with much less data in pediatric TOF than adults, this pilot trial sets the stage to create a prospective randomized trial in the teenage years.

Condition or disease Intervention/treatment Phase
Tetralogy of Fallot Procedure: PVR Not Applicable

Detailed Description:

The purpose of this research study is to gather information on adolescents and young adults to help understand and improve the lives of patients with TOF.

Some patients diagnosed with TOF will have a procedure called pulmonary valve replacement (PVR) and some will not. PVR is done for valves that are too damaged to be repaired. This requires a surgeon or an expert in a procedure called cardiac catheterization to replace the damaged pulmonary valve with a valve made of tissue or amechanical valve. Multiple studies in adult TOF patients have suggested that PVR may lessen many clinical symptoms but no one is sure if it truly does. There is little information about PVR in adolescence but it is thought that lessening the amount of leakage of the pulmonary valve at a young age may avoid future complications such as right heart failure or abnormal beats of your heart. There is no agreement among cardiologists, surgeons or other healthcare providers as to whether PVR truly helps avoid complications in the future and if it does, when PVR should be done. Using the information in this study, we hope to find out if PVR in adolescents is helpful in both the short and long term.

The Investigators believe the results of this study will help provide doctors with enough information to support a future large scale research study to further evaluate the outcomes PVR. This study will involve randomization to either the PVR or no PVR cohort, medical records review, exercise test and Cardiac Magnetic Resonance (CMR) , and questionnaires.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Subjects will be randomized to PVR or no PVR
Masking: Single (Investigator)
Masking Description: Subjects will be randomly assigned to one of two groups. One will undergo PVR with catheter or surgery (whichever is most appropriate ). The other group will continue with medical management.
Primary Purpose: Treatment
Official Title: Pediatric REPlAcement of the PulmonaRy ValvE in Tetralogy of Fallot - The PREPARE-TOF Study
Actual Study Start Date : July 6, 2018
Actual Primary Completion Date : January 16, 2021
Actual Study Completion Date : January 16, 2021

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
PVR arm will undergo PVR via catheter or surgery
Procedure: PVR
Subjects will undergo PVR via surgery or cardiac catheterization. PVR using cardiac catheterization may require a much shorter hospital stay than traditional heart surgery. If the valve is repaired by surgery, this will require open heart surgery to directly implant a pulmonary valve

No Intervention: No PVR
No PVR group will continue with medical management

Primary Outcome Measures :
  1. Operational feasibility of a randomized multicenter trial [ Time Frame: 2-3 years ]
    The operational feasibility will be assessed by the ability to recruit the required number of patients in the time given (recruiting the full complement of 90 patients over 18 months across 5 centers (ie 1 patient per month per center) to achieve 500 patients across 8 centers over the course of 2-3 years in the larger definitive trial

Secondary Outcome Measures :
  1. Exercise performances [ Time Frame: 12-18 months ]
    This will be determined by exercise test performed to assess parameters such as oxygen consumption (VO2) at ventilatory anaerobic threshold (VAT) and normalized for age

  2. Prevalence of arrhythmias [ Time Frame: 12-18 months ]
    This will be determined by reviewing Holter monitoring data the assess the prevalence of arrhythmias. This will also provide the endpoints for the larger, longer term trial

  3. Effects of PVR on Diffuse Fibrosis [ Time Frame: 12-18 months ]
    This will be measured by obtaining preliminary data on the difference between patients randomized to PVR and no PVR in regard to diffuse fibrosis (DF).

  4. Effects of PVR on exercise in the Magnetic Resonance (MR) scanner [ Time Frame: 12-18 months ]
    Mechanisms of the effects of PVR in the definitive trial will be measured by obtaining preliminary data on the difference between patients randomized to PVR and no PVR in regard to performing exercise CMR.

  5. Effects of PVR on Biventricular Strain [ Time Frame: 12-18 months ]
    Mechanisms of the effects of PVR in the definitive trial will be measured by obtaining preliminary data on biventricular strain.

  6. Quality of Life (QOL) [ Time Frame: 12-18 months ]
    Quality of life will be measured using the Pediatric Cardiac Quality of Life Inventory (PCQLI) - to measure quality of life. The PCQLI has been used for over 10 years and is a validated quality of life metric. The PCQLI measures disease-specific, pediatric health related quality of life and generates 3 scores, namely, total, disease impact subscale, and psychosocial impact subscale. Each subscale score has a maximum of 50 points, and their sum yields the total score. Higher scores represent better perceived pediatric health related quality of life

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   13 Years to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Males or females with repaired Tetralogy of Fallot (TOF), currently between 13 and 21 years of age.
  2. On clinical Cardiac Magnetic Resonance (CMR) : Right Ventricular End-Diastolic Volume Index (RVEDVi) between 140 and 180 cc/m2 inclusive with Right Ventricular End-Diastolic Function (RVEF) > 40% and Left Right Ventricular End-Diastolic (LVEF ) > 50%, RV outflow tract peak velocity < 3 meters/second (if not available this will be skipped); there will be no indexed Right Ventricular end-systolic volume (RVESVi) criteria; by defining RVEDVi and RVEF, Investigators will be inherently defining RVESVi
  3. On clinical echocardiogram: RV outflow tract peak velocity < 3 meters/second (if not available this will be skipped), at least mild pulmonary insufficiency and tricuspid regurgitation with an RV pressure estimate < 1/2 systemic pressure.
  4. On Exercise Stress Test (EST), aerobic capacity > 60% of predicted.
  5. No Q-wave, R-wave, S-wave (QRS) duration criteria on ECG.

Exclusion Criteria:

  1. Any condition judged by the patient's physician that would cause this trial to be detrimental to the patient.
  2. Specific forms of TOF excluded are those with endocardial cushion defects, TOF with absent pulmonary valve and TOF with multiple aorto-pulmonary collaterals requiring unifocalization.
  3. Unilateral branch pulmonary artery stenosis (one lung receives < 25% of total flow)
  4. Contraindication to non-sedated exercise CMR (e.g. pacemaker/implanted cardioverter defibrillator); need for sedation
  5. If data available, moderate or greater tricuspid regurgitation on echocardiogram or CMR or Qp/Qs > 1.5
  6. Significant strokes/hemiplegia or inability to exercise
  7. Genetic syndrome/developmental delay which would make QOL and EST date uninterpretable
  8. Pregnancy
  9. Previous pulmonary valve replacement (PVR)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03634072

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United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010
United States, Georgia
Children's Healthcare of Atlanta
Atlanta, Georgia, United States, 30322
United States, Illinois
Lurie Children's Hospital of Chicago
Chicago, Illinois, United States, 60611
Northwestern University
Chicago, Illinois, United States, 60611
United States, Ohio
Cincinnati Children's Hosptial Medical Center
Cincinnati, Ohio, United States, 45229
United States, Pennsylvania
The Childrens Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Children's Hospital of Philadelphia
National Heart, Lung, and Blood Institute (NHLBI)
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Principal Investigator: Mark Fogel, MD The Childrens Hospital of Philadelphia
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Responsible Party: Children's Hospital of Philadelphia Identifier: NCT03634072    
Other Study ID Numbers: 18-015046
R34HL142142-01 ( U.S. NIH Grant/Contract )
First Posted: August 16, 2018    Key Record Dates
Last Update Posted: September 17, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The Principal Investigator (PI) is responsible for data management and accuracy of records. The PI may assign designated qualified individuals to collect the information. Only investigators' on this protocol and assigned research staff on this protocol will have access to the data. Data will be entered into a REDcap database by a member of the study team. All data and records generated during this study will be kept confidential in accordance with Institutional and HIPAA policies on subject privacy. The study team will not use such data and records for any purpose other than conducting the study. In order to keep protected health information from disclosure, each patient will be given a unique identification number. The key to this code will be kept in a locked file in one of the study investigator's offices. Any data that is transmitted to any Data Coordinating Center (DCC) will be de-identified by the enrolling site
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: 2-3 years
Access Criteria: All future studies using these patients will require separate Institutional Review Board (IRB) approved protocols and consent forms. Only investigators' on this protocol and assigned research staff on this protocol will have access to the data

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Tetralogy of Fallot
Heart Defects, Congenital
Cardiovascular Abnormalities
Cardiovascular Diseases
Heart Diseases
Congenital Abnormalities