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

Primary Purpose

Tetralogy of Fallot

Status

Terminated

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

PVR

About this trial

This is an interventional treatment trial for Tetralogy of Fallot

Eligibility Criteria

13 Years - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Males or females with repaired Tetralogy of Fallot (TOF), currently between 13 and 21 years of age.
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
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.
On Exercise Stress Test (EST), aerobic capacity > 60% of predicted.
No Q-wave, R-wave, S-wave (QRS) duration criteria on ECG.

Exclusion Criteria:

Any condition judged by the patient's physician that would cause this trial to be detrimental to the patient.
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.
Unilateral branch pulmonary artery stenosis (one lung receives < 25% of total flow)
Contraindication to non-sedated exercise CMR (e.g. pacemaker/implanted cardioverter defibrillator); need for sedation
If data available, moderate or greater tricuspid regurgitation on echocardiogram or CMR or Qp/Qs > 1.5
Significant strokes/hemiplegia or inability to exercise
Genetic syndrome/developmental delay which would make QOL and EST date uninterpretable
Pregnancy
Previous pulmonary valve replacement (PVR)

Sites / Locations

Children's National Medical Center
Children's Healthcare of Atlanta
Lurie Children's Hospital of Chicago
Northwestern University
Cincinnati Children's Hosptial Medical Center
The Childrens Hospital of Philadelphia

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

No Intervention

Arm Label

PVR Arm

No PVR

Arm Description

PVR arm will undergo PVR via catheter or surgery

No PVR group will continue with medical management

Outcomes

Primary Outcome Measures

Number of Participants Randomized to PVR Via Catheter or Surgery

Participants will be randomized by computer by the statistician at the Data Coordinating Center (DCC) at Northwestern University (NU) who will maintain the schedule; this will be a 2:1 randomization of PVR to no-PVR. There will be no blinding and the assignment will not be concealed from the investigators. There will be no stratifications within each group.

Secondary Outcome Measures

Exercise Performances

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

Prevalence of Arrhythmias

This will be determined by reviewing Holter monitoring data to assess the prevalence of arrhythmias. This will also provide the endpoints for the larger, longer term trial

Effects of Pulmonary Valve Replacement (PVR) on Diffuse Fibrosis

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).

Effects of PVR on Exercise in the Magnetic Resonance (MR) Scanner

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 cardiac magnetic resonance (CMR).

Effects of PVR on Biventricular Strain

Mechanisms of the effects of PVR in the definitive trial will be measured by obtaining preliminary data on biventricular strain.

Quality of Life (QOL)

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

Full Information

NCT ID

NCT03634072

First Posted

August 2, 2018

Last Updated

September 14, 2023

Sponsor

Children's Hospital of Philadelphia

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

1. Study Identification

Unique Protocol Identification Number

NCT03634072

Brief Title

Pediatric REPlAcement of the PulmonaRy ValvE in Tetralogy of Fallot -

Acronym

TOFandPVR

Official Title

Pediatric REPlAcement of the PulmonaRy ValvE in Tetralogy of Fallot - The PREPARE-TOF Study

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Terminated

Why Stopped

Unable to meet enrollment goal

Study Start Date

July 6, 2018 (Actual)

Primary Completion Date

January 16, 2021 (Actual)

Study Completion Date

January 16, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Children's Hospital of Philadelphia

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

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 (PVR) 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.

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 a mechanical 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Tetralogy of Fallot

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Model Description

Subjects will be randomized to PVR or no PVR

Masking

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.

Allocation

Randomized

Enrollment

1 (Actual)

8. Arms, Groups, and Interventions

Arm Title

PVR Arm

Arm Type

Other

Arm Description

PVR arm will undergo PVR via catheter or surgery

Arm Title

No PVR

Arm Type

No Intervention

Arm Description

No PVR group will continue with medical management

Intervention Type

Procedure

Intervention Name(s)

PVR

Intervention Description

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

Primary Outcome Measure Information:

Title

Number of Participants Randomized to PVR Via Catheter or Surgery

Description

Time Frame

2-3 years

Secondary Outcome Measure Information:

Title

Exercise Performances

Description

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

Time Frame

12-18 months

Title

Prevalence of Arrhythmias

Description

This will be determined by reviewing Holter monitoring data to assess the prevalence of arrhythmias. This will also provide the endpoints for the larger, longer term trial

Time Frame

12-18 months

Title

Effects of Pulmonary Valve Replacement (PVR) on Diffuse Fibrosis

Description

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).

Time Frame

12-18 months

Title

Effects of PVR on Exercise in the Magnetic Resonance (MR) Scanner

Description

Time Frame

12-18 months

Title

Effects of PVR on Biventricular Strain

Description

Mechanisms of the effects of PVR in the definitive trial will be measured by obtaining preliminary data on biventricular strain.

Time Frame

12-18 months

Title

Quality of Life (QOL)

Description

Time Frame

12-18 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

13 Years

Maximum Age & Unit of Time

21 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Males or females with repaired Tetralogy of Fallot (TOF), currently between 13 and 21 years of age. 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 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. On Exercise Stress Test (EST), aerobic capacity > 60% of predicted. No Q-wave, R-wave, S-wave (QRS) duration criteria on ECG. Exclusion Criteria: Any condition judged by the patient's physician that would cause this trial to be detrimental to the patient. 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. Unilateral branch pulmonary artery stenosis (one lung receives < 25% of total flow) Contraindication to non-sedated exercise CMR (e.g. pacemaker/implanted cardioverter defibrillator); need for sedation If data available, moderate or greater tricuspid regurgitation on echocardiogram or CMR or Qp/Qs > 1.5 Significant strokes/hemiplegia or inability to exercise Genetic syndrome/developmental delay which would make QOL and EST date uninterpretable Pregnancy Previous pulmonary valve replacement (PVR)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Mark Fogel, MD

Organizational Affiliation

The Childrens Hospital of Philadelphia

Official's Role

Principal Investigator

Facility Information:

Facility Name

Children's National Medical Center

City

Washington

State/Province

District of Columbia

ZIP/Postal Code

20010

Country

United States

Facility Name

Children's Healthcare of Atlanta

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30322

Country

United States

Facility Name

Lurie Children's Hospital of Chicago

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60611

Country

United States

Facility Name

Northwestern University

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60611

Country

United States

Facility Name

Cincinnati Children's Hosptial Medical Center

City

Cincinnati

State/Province

Ohio

ZIP/Postal Code

45229

Country

United States

Facility Name

The Childrens Hospital of Philadelphia

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing 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

IPD Sharing Time Frame

2-3 years

IPD Sharing 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

Learn more about this trial

Pediatric REPlAcement of the PulmonaRy ValvE in Tetralogy of Fallot -

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