Clinical trial NCT04084132: Early Versus Later Re-valving in Tetralogy of Fallot With Free Pulmonary Regurgitation
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Tetralogy of Fallot
Pulmonary Regurgitation
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: Aarhus University Hospital
name: Odense University Hospital
First posted: 2019-09-10
Enrollment: 120
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. ToF with pulmonary stenosis repaired with a TAP within the first two years of life.
2. RVOT anatomy is suitable for implantation of an adult sized conduit ( 18 mm homograft or Contegra graft) as assessed by MRI.

Exclusion Criteria:

1. ToF with pulmonary atresia, ToF with common atrioventricular canal, ToF with absent pulmonary valve syndrome, major aortopulmonary collateral arteries and other significant associated anomalies.
2. Palliation with a shunt (Blalock-Taussig or central) at any time.
3. The patient is symptomatic.
4. Sustained supraventricular or ventricular arrhythmia.
5. RVEDVi \> 140 mL/m2 as assessed by MRI (appendix 1).
6. RVESVi \> 60 mL/m2 as assessed by MRI.
7. RVEF \< 50 % as assessed by MRI.
8. Moderate or severe tricuspid regurgitation as assessed by echocardiography or MRI.
9. Significant residual lesions requiring intervention (e.g. ventricular septal defect, aortic regurgitation, branch pulmonary artery stenosis).
10. Co-morbidity preventing exercise testing (e.g. genetics, neuro-cognitive dysfunction, physical disability).
11. Contraindication for MRI (e.g. permanent pacemaker, intra-cardiac defibrillator, intracranial ferro-magnetic device).
12. Pregnancy at time of inclusion.
13. Age \< 12 or unable to comply with instructions given during MRI or exercise testing.

Primary outcomes:
measure: Mean right ventricular end-diastolic volume indexed to body surface area
timeFrame: 3 years after randomization
measure: Rate of deceased patients (all-cause mortality) and total number of patients
timeFrame: 3 years after randomization
Secondary outcomes:
measure: Right ventricular end-systolic volume indexed to body surface area
timeFrame: Assessed once every year for 10 years after randomization
measure: Right ventricular ejection fraction
timeFrame: Assessed once every year for 10 years after randomization
measure: Left ventricular end-diastolic volume indexed to body surface area
timeFrame: Assessed once every year for 10 years after randomization
measure: Left ventricular end-systolic volume indexed to body surface area
timeFrame: Assessed once every year for 10 years after randomization
measure: Left ventricular ejection fraction
timeFrame: Assessed once every year for 10 years after randomization
measure: Rate of patients with procedure-related bleeding and total number of patients
timeFrame: 30 days after surgery
measure: Rate of patients with procedure-related acute kidney injury and total number of patients.
timeFrame: 30 days after surgery
measure: Composite-rate of all-cause mortality and disabling stroke
timeFrame: Assessed once every year for 10 years after randomization
measure: Rate of patients deceased due to cardiovascular causes and total number of patients
timeFrame: Assessed once every year for 10 years after randomization
measure: Composite-rate of patients who suffer from disabling strokes or transient ischemic attacks
timeFrame: Assessed once every year for 10 years after randomization
measure: Mean New York Heart Association class
timeFrame: Assessed once every year for 10 years after randomization
measure: Mean health-associated quality of life (adults)
timeFrame: Assessed once every year for 10 years after randomization
measure: Mean health-associated quality of life (children)
timeFrame: Assessed once every year for 10 years after randomization
measure: Rate of patients with new sustained supraventricular or ventricular arrhythmia and the total number of patients
timeFrame: Assessed once every year for 10 years after randomization
measure: Mean peak oxygen consumption during cardiopulmonary exercise testing
timeFrame: Assessed once every year for 10 years after randomization
measure: Median time until structural valve deterioration in patients who are re-valved during the study
timeFrame: Assessed once every year for 10 years after randomization
measure: 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
timeFrame: Assessed once every year for 10 years after randomization
measure: 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
timeFrame: Assessed once every year for 10 years after randomization
measure: Mean number of contacts to the health system
timeFrame: Assessed once every year for 10 years after randomization
measure: Mean number of children for female patients
timeFrame: Assessed once every year for 10 years after randomization
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Odense
country: Denmark
facility: Odense University Hospital
Study officials:
affiliation: Rigshospitalet, Denmark
name: Lars Søndergaard, MD, DMSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Rigshospitalet, Denmark
name: Morten H Smerup, MD, PhD
role: STUDY_CHAIR
affiliation: Aarhus University Hospital
name: Dorte G Nielsen, MD, PhD
role: STUDY_CHAIR
affiliation: Aarhus University Hospital
name: Kim Munk, MD, PhD
role: STUDY_CHAIR
affiliation: Odense University Hospital
name: Henrik Nissen, MD, PhD
role: STUDY_CHAIR
affiliation: Odense University Hospital
name: Helle Andersen, MD
role: STUDY_CHAIR
References: