Early Versus Later Re-valving in Tetralogy of Fallot With Free Pulmonary Regurgitation - Combined Cross-sectional and Prospective, Multi-centre, Randomized, Parallel-group Clinical Trial
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Tetralogy of Fallot
- Sponsor
- Rigshospitalet, Denmark
- Enrollment
- 120
- Locations
- 3
- Primary Endpoint
- Rate of deceased patients (all-cause mortality) and total number of patients
- Status
- Recruiting
- Last Updated
- 6 years ago
Overview
Brief Summary
Tetralogy of Fallot (ToF) is a congenital heart defect with four major features including right ventricular outflow tract obstruction. About 25 children are born with this condition in Denmark every year. Corrective surgery is usually performed within the first year. In 50 % of patients, enlargement with a patch is necessary to achieve relief of the outflow tract obstruction. This however results in severe pulmonary regurgitation, which eventually leads to volume overload, right ventricular dysfunction and arrhythmia. To avoid these late complications, pulmonary valve replacement with a prosthesis if performed when patients meet the current guideline criteria. Most patients meet the guideline criteria for revalving when they are between 20 and 30 years of age. The current guidelines however, are based solely on retrospective studies and novel research reveals that in more than 50 % of patients who are treated according to current practice, right ventricular volumes and function as well as exercise capacity and burden of arrhythmia do not normalize or improve. 500 patients with ToF will be enrolled in a multicentre, cross-sectional study, which will yield information about the long-term outcomes after initial repair of ToF, as well as suggestions about the optimal timing for re-valving. Among patients included in the cross-sectional study, 120 patients with free pulmonary regurgitation, will be randomized evenly for early or later re-valving with at least 10-years of follow-up, for evaluation of long-term efficacy and safety of early re-valving.
Investigators
Lars Soendergaard
Clinical Professor, Consultant MD, DMSc
Rigshospitalet, Denmark
Eligibility Criteria
Inclusion Criteria
- •ToF with pulmonary stenosis repaired with a TAP within the first two years of life.
- •RVOT anatomy is suitable for implantation of an adult sized conduit ( 18 mm homograft or Contegra graft) as assessed by MRI.
Exclusion Criteria
- •ToF with pulmonary atresia, ToF with common atrioventricular canal, ToF with absent pulmonary valve syndrome, major aortopulmonary collateral arteries and other significant associated anomalies.
- •Palliation with a shunt (Blalock-Taussig or central) at any time.
- •The patient is symptomatic.
- •Sustained supraventricular or ventricular arrhythmia.
- •RVEDVi \> 140 mL/m2 as assessed by MRI (appendix 1).
- •RVESVi \> 60 mL/m2 as assessed by MRI.
- •RVEF \< 50 % as assessed by MRI.
- •Moderate or severe tricuspid regurgitation as assessed by echocardiography or MRI.
- •Significant residual lesions requiring intervention (e.g. ventricular septal defect, aortic regurgitation, branch pulmonary artery stenosis).
- •Co-morbidity preventing exercise testing (e.g. genetics, neuro-cognitive dysfunction, physical disability).
Outcomes
Primary Outcomes
Rate of deceased patients (all-cause mortality) and total number of patients
Time Frame: 3 years after randomization
The rate of deceased patients (irrespective of the cause of death) and total number of patients will be calculated for both the early and later re-valving group and analysis of statistical significance of the difference between the groups will be performed.
Mean right ventricular end-diastolic volume indexed to body surface area
Time Frame: 3 years after randomization
Right ventricular end-diastolic volume (mL) indexed by body surface area (m2) will be assessed in both the early re-valving group and later re-valving group for calculation of the mean in each group and analysis of statistical significance of the difference will be performed. Higher right ventricular end-diastolic volumes are considered a worse outcome.
Secondary Outcomes
- Rate of patients with procedure-related acute kidney injury and total number of patients.(30 days after surgery)
- Right ventricular end-systolic volume indexed to body surface area(Assessed once every year for 10 years after randomization)
- Left ventricular end-diastolic volume indexed to body surface area(Assessed once every year for 10 years after randomization)
- Left ventricular end-systolic volume indexed to body surface area(Assessed once every year for 10 years after randomization)
- Composite-rate of all-cause mortality and disabling stroke(Assessed once every year for 10 years after randomization)
- Mean New York Heart Association class(Assessed once every year for 10 years after randomization)
- Right ventricular ejection fraction(Assessed once every year for 10 years after randomization)
- Rate of patients who are re-valved during the course of the study and suffer from endocarditis and the total number of patients who are revalved during the study(Assessed once every year for 10 years after randomization)
- Rate of patients with procedure-related bleeding and total number of patients(30 days after surgery)
- Rate of patients deceased due to cardiovascular causes and total number of patients(Assessed once every year for 10 years after randomization)
- Left ventricular ejection fraction(Assessed once every year for 10 years after randomization)
- Composite-rate of patients who suffer from disabling strokes or transient ischemic attacks(Assessed once every year for 10 years after randomization)
- Median time until structural valve deterioration in patients who are re-valved during the study(Assessed once every year for 10 years after randomization)
- Mean health-associated quality of life (adults)(Assessed once every year for 10 years after randomization)
- Mean health-associated quality of life (children)(Assessed once every year for 10 years after randomization)
- Rate of patients with new sustained supraventricular or ventricular arrhythmia and the total number of patients(Assessed once every year for 10 years after randomization)
- Mean peak oxygen consumption during cardiopulmonary exercise testing(Assessed once every year for 10 years after randomization)
- Mean number of contacts to the health system(Assessed once every year for 10 years after randomization)
- Mean number of children for female patients(Assessed once every year for 10 years after randomization)
- Rate of patients who are re-valved during the course of the study and suffer from prosthetic valve thrombosis and the total number of patients who are revalved during the study(Assessed once every year for 10 years after randomization)