Early Versus Later Re-valving in Tetralogy of Fallot With Free Pulmonary Regurgitation

NCT04084132 | Recruiting

• 1 other identifier: VD-2018-512
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 3

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.

Conditions

Tetralogy of Fallot; Pulmonary Regurgitation

Outcome Measures

Primary Outcomes (2)

• Mean right ventricular end-diastolic volume indexed to body surface area

  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.

  3 years after randomization

• Rate of deceased patients (all-cause mortality) and total number of patients

  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.

  3 years after randomization

Secondary Outcomes (20)

• Right ventricular end-systolic volume indexed to body surface area

  Assessed once every year for 10 years after randomization

• Right ventricular ejection fraction

  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

• Left ventricular ejection fraction

  Assessed once every year for 10 years after randomization

Study Arms (2)

Early re-valving

EXPERIMENTAL

60 patients who are assigned to early re-valving undergo pulmonary valve replacement within 3 months from randomization.

Procedure: Pulmonary valve replacement

Later re-valving

EXPERIMENTAL

60 patients who are assigned to later re-valving undergo pulmonary valve replacement when the current European guideline criteria are met.

Procedure: Pulmonary valve replacement

Interventions

Pulmonary valve replacement PROCEDURE

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.

Early re-valving; Later re-valving

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).
• Age \< 12 or unable to comply with instructions given during MRI or exercise testing.

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead
• Aarhus University Hospital: collaborator
• Odense University Hospital: collaborator

Study Sites (3)

Aarhus University Hospital

Aarhus, 8200, Denmark

NOT YET RECRUITING

Rigshospitalet

Copenhagen, 2100, Denmark

RECRUITING

Odense University Hospital

Odense, 5000, Denmark

NOT YET RECRUITING

MeSH Terms

Conditions

Tetralogy of Fallot; Pulmonary Valve Insufficiency

Condition Hierarchy (Ancestors)

Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heart Valve Diseases

Study Officials

• Lars Søndergaard, MD, DMSc

  Rigshospitalet, Denmark

  PRINCIPAL INVESTIGATOR

• Morten H Smerup, MD, PhD

  Rigshospitalet, Denmark

  STUDY CHAIR

• Dorte G Nielsen, MD, PhD

  Aarhus University Hospital

  STUDY CHAIR

• Kim Munk, MD, PhD

  Aarhus University Hospital

  STUDY CHAIR

• Henrik Nissen, MD, PhD

  Odense University Hospital

  STUDY CHAIR

• Helle Andersen, MD

  Odense University Hospital

  STUDY CHAIR

Central Study Contacts

Mathis Gröning, MD, DMSc

CONTACT

+45 42404489; mathis.groening@regionh.dk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor, Consultant MD, DMSc

Study Record Dates

• First Submitted: February 25, 2019
• First Posted: September 10, 2019
• Study Start: April 1, 2019
• Primary Completion: December 31, 2024
• Study Completion (Estimated): December 31, 2031
• Last Updated: September 10, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share

Locations

DK (3)