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

Overview

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.

Interventions

• Procedure Pulmonary valve replacement
  Surgical implantation of an adult-sized (≥ 18 mm) homograft or Contegra graft as right ventricle-to-pulmonary artery conduit under cardiopulmonary bypass through a sternotomy.

Primary outcome measures

• Mean right ventricular end-diastolic volume indexed to body surface area [Time frame: 3 years after randomization]
• Rate of deceased patients (all-cause mortality) and total number of patients [Time frame: 3 years after randomization]

Secondary outcome measures (12)

• Right ventricular end-systolic volume indexed to body surface area [Time frame: Assessed once every year for 10 years after randomization]
• Right ventricular ejection fraction [Time frame: Assessed once every year for 10 years after randomization]
• Left ventricular end-diastolic volume indexed to body surface area [Time frame: Assessed once every year for 10 years after randomization]
• Left ventricular end-systolic volume indexed to body surface area [Time frame: Assessed once every year for 10 years after randomization]
• Left ventricular ejection fraction [Time frame: Assessed once every year for 10 years after randomization]
• Rate of patients with procedure-related bleeding and total number of patients [Time frame: 30 days after surgery]
• Rate of patients with procedure-related acute kidney injury and total number of patients. [Time frame: 30 days after surgery]
• Composite-rate of all-cause mortality and disabling stroke [Time frame: Assessed once every year for 10 years after randomization]
• Rate of patients deceased due to cardiovascular causes and total number of patients [Time frame: Assessed once every year for 10 years after randomization]
• Composite-rate of patients who suffer from disabling strokes or transient ischemic attacks [Time frame: Assessed once every year for 10 years after randomization]
• Mean New York Heart Association class [Time frame: Assessed once every year for 10 years after randomization]
• Mean health-associated quality of life (adults) [Time frame: Assessed once every year for 10 years after randomization]

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).
• Contraindication for MRI (e.g. permanent pacemaker, intra-cardiac defibrillator, intracranial ferro-magnetic device).
• Pregnancy at time of inclusion.
• Age < 12 or unable to comply with instructions given during MRI or exercise testing.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Denmark · 3 centers

• Aarhus University Hospital — Aarhus
• Rigshospitalet — Copenhagen
• Odense University Hospital — Odense

Identifiers

NCT: NCT04084132 · VD-2018-512

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗