Tetralogy of Fallot
Conditions
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.
Interventions
PROCEDUREPVR
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
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Children's Hospital of Philadelphia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
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.
Intervention model description
Subjects will be randomized to PVR or no PVR
Eligibility
Sex/Gender
ALL
Age
13 Years to 21 Years
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Randomized to PVR Via Catheter or Surgery | 2-3 years | 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
| Measure | Time frame | Description |
|---|---|---|
| Prevalence of Arrhythmias | 12-18 months | 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 | 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). |
| Exercise Performances | 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 |
| Effects of PVR on Biventricular Strain | 12-18 months | Mechanisms of the effects of PVR in the definitive trial will be measured by obtaining preliminary data on biventricular strain. |
| Quality of Life (QOL) | 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 |
| Effects of PVR on Exercise in the Magnetic Resonance (MR) Scanner | 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 cardiac magnetic resonance (CMR). |
Countries
United States
Participant flow
Recruitment details
Patient was enrolled in 2020 in clinic
Pre-assignment details
No pre-assignment issues were found
Participants by arm
| Arm | Count |
|---|---|
| PVR Arm PVR arm will undergo PVR via catheter or surgery
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.
1 patient was enrolled in this arm from Emory University | 1 |
| No PVR No PVR group will continue with medical management
No patients were enrolled in this group. | 0 |
| Total | 1 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Early termination of overall study | 1 | 0 |
Baseline characteristics
| Characteristic | No PVR | PVR Arm | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | — | 17 years STANDARD_DEVIATION 0 | 16 years STANDARD_DEVIATION 0 |
| Race (NIH/OMB) American Indian or Alaska Native | — | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | — | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | — | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | — | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | — | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | — | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | — | 1 Participants | 1 Participants |
| Region of Enrollment United States | — | 1 participants | 1 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 0 Participants | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 0 |
| other Total, other adverse events | 0 / 1 | 0 / 0 |
| serious Total, serious adverse events | 0 / 1 | 0 / 0 |
Outcome results
Primary
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.
Time frame: 2-3 years
Population: One subject was randomized to the PVR arm; however, no data was collected to analyze
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PVR Arm | Number of Participants Randomized to PVR Via Catheter or Surgery | 0 PVR via catheter or surgery |
Secondary
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).
Time frame: 12-18 months
Population: No data were collected and no intervention completed in the PVR arm.
Secondary
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.
Time frame: 12-18 months
Population: No data were collected and no intervention completed in the PVR arm.
Secondary
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).
Time frame: 12-18 months
Population: No data were collected and no intervention completed in the PVR arm.
Secondary
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
Time frame: 12-18 months
Population: No data were collected and no intervention completed in the PVR arm.
Secondary
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
Time frame: 12-18 months
Population: No data were collected and no intervention completed in the PVR arm.
Secondary
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
Time frame: 12-18 months
Population: No data were collected and no intervention completed in the PVR arm.