Tetralogy of FallotNCT04084132
Early Versus Later Re-valving in Tetralogy of Fallot With Free Pulmonary Regurgitation
A study testing Pulmonary valve replacement in people with Tetralogy of Fallot and Pulmonary Regurgitation, run by Copenhagen University Hospital, Rigshospitalet at 3 sites in Denmark.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Tetralogy of Fallot, Pulmonary Regurgitation
- What is being tested?
- Pulmonary valve replacement
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 3 sitesDenmark
- Study dates
- 1 Apr 2019to 31 Dec 2031
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 13Show fewer
- 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.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Denmark3 sites, 3 recruiting
- Not yet recruiting
Aarhus University Hospital
Aarhus, 8200
Dorte G Nielsen, MD, PhD
Dorte G Nielsen, MD, PhD
- Recruiting
Rigshospitalet
Copenhagen, 2100
Mathis Gröning, MD, +45 35456238, mathis.groening@regionh.dk
Lars Søndergaard, Professor
- Not yet recruiting
Odense University Hospital
Odense, 5000
Henrik Nissen, MD, PhD
Henrik Nissen, MD, PhD
About this study
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
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
- Being tested
- Pulmonary valve replacement
- Medical subject headings
- Tetralogy of Fallot, Pulmonary Valve Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pulmonary valve replacementProcedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| Early re-valving | Experimental | 60 patients who are assigned to early re-valving undergo pulmonary valve replacement within 3 months from randomization. Receives: 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. Receives: Procedure: Pulmonary valve replacement |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 3 years after randomization
Secondary outcomes (20)
Right ventricular end-systolic volume indexed to body surface area
Right ventricular end-systolic 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-systolic volumes are considered a worse outcome.
Measured: Assessed once every year for 10 years after randomization
Right ventricular ejection fraction
Right ventricular ejection fraction (%) 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. Lower right ventricular ejection fraction are considered a worse outcome.
Measured: Assessed once every year for 10 years after randomization
Left ventricular end-diastolic volume indexed to body surface area
Left 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 left ventricular end-diastolic volumes are considered a worse outcome.
Measured: Assessed once every year for 10 years after randomization
Left ventricular end-systolic volume indexed to body surface area
Left 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 left ventricular end-systolic volumes are considered a worse outcome.
Measured: Assessed once every year for 10 years after randomization
Left ventricular ejection fraction
Left ventricular ejection fraction (%) 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. Lower left ventricular ejection fraction are considered a worse outcome.
Measured: Assessed once every year for 10 years after randomization
Rate of patients with procedure-related bleeding and total number of patients
The rate of patients with bleeding classified as minor, major and life-threatening bleeding (BARC classification) related to the re-valving procedure and the total number of patients will be calculated in both the early and later re-valving group and the difference between the groups will be analyzed for statistical significance.
Measured: 30 days after surgery
Rate of patients with procedure-related acute kidney injury and total number of patients.
The rate of acute kidney injury categorized as stage one, two and three (KDIGO classification) and the total number of patients will be calculated in both the early and later re-valving group and the difference will be analyzed for statistical significance.
Measured: 30 days after surgery
Composite-rate of all-cause mortality and disabling stroke
The rate of patients who decease due to cardiovascular causes and patients who suffer from a disabling stroke after the time of randomization will be calculated for both the early and later re-valving group and the difference will be analyzed for statistical significance
Measured: Assessed once every year for 10 years after randomization
Rate of patients deceased due to cardiovascular causes and total number of patients
The rate of patients who decease due to a cardiovascular cause and the total number of patients will be calculated in both the early and later re-valving group and the difference will be analyzed for statistical significance
Measured: Assessed once every year for 10 years after randomization
Composite-rate of patients who suffer from disabling strokes or transient ischemic attacks
The rate of patients who suffer from a disabling stroke og transient ischemic attack after the time of randomization will be calculated in both the early and later re-valving group and the difference will be analyzed for statistical significance
Measured: Assessed once every year for 10 years after randomization
Mean New York Heart Association class
The mean New York Heart Association Class categorized as 1-4 will be assessed in both the early and later re-valving group and the difference will be analyzed for statistical significance. Higher mean values are considered a worse outcome.
Measured: Assessed once every year for 10 years after randomization
Mean health-associated quality of life (adults)
The mean health-asssociated quality of life will be assessed in both the early and later revalving group and the difference will be analyzed for statistical significance. EQ-5D-3L will be used for assessment. The questionnaires are available in Danish. Higher values are considered better outcomes.
Measured: Assessed once every year for 10 years after randomization
Mean health-associated quality of life (children)
The mean health-associated quality of life will be assessed in both the early and later re-valving group and the difference will be analyzed for statistical significance. EQ-5D-Y will be used for assessment. The questionnaires are available in Danish. Higher values are considered better outcomes.
Measured: 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
The rate of patients with new supraventricular or ventricular arrhythmia and the total number of patients will be calculated for both the early and later re-valving group and the difference will be analyzed for statistical significance.
Measured: Assessed once every year for 10 years after randomization
Mean peak oxygen consumption during cardiopulmonary exercise testing
The mean peak oxygen consumption (VO2/min) indexed to body weight (kg) will be assessed for patients in both the early and later re-valving group and the difference in means will be analyzed for statistical significance. Higher mean values are considered a better outcomes.
Measured: Assessed once every year for 10 years after randomization
Median time until structural valve deterioration in patients who are re-valved during the study
The median time until structural valve deterioration defined as time until need for valve replacement in patients who are revalved during the study will be calculated.
Measured: 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
The rate of patients who suffer from endocarditis after re-valving during the course of the study and the total number of patients who are revalved during the study will be calculated
Measured: 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
The rate of patients who suffer from prosthetic valve thrombosis after re-valving during the course of the study and the total number of patients who are revalved during the study will be calculated
Measured: Assessed once every year for 10 years after randomization
Mean number of contacts to the health system
The mean number of contacts to the health system defined as composite of hospital admissions, outpatient contacts and contacts to the general practitioner will be calculated in both the early and later re-valving group and the difference will be analyzed for statistical significance
Measured: Assessed once every year for 10 years after randomization
Mean number of children for female patients
The mean number of children will be assessed for female patient in both the early and later re-valving group and the difference will be analyzed for statistical significance
Measured: Assessed once every year for 10 years after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2019
- Study start1 Apr 2019
- Primary completion31 Dec 2024 (estimated)
- Study completion31 Dec 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Tetralogy of FallotStudies of the same condition, open and under way.
- More trials run by Copenhagen University Hospital, RigshospitaletThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Copenhagen University Hospital, Rigshospitalet
- Sponsor type
- University, hospital or other
- Collaborators
- Aarhus University Hospital, Odense University Hospital
- Responsible party
- Principal investigator, Lars Soendergaard, Copenhagen University Hospital, Rigshospitalet
- Investigators
- Lars Søndergaard, MD, DMSc, Principal investigator, Copenhagen University Hospital, RigshospitaletMorten H Smerup, MD, PhD, Study chair, Copenhagen University Hospital, RigshospitaletDorte G Nielsen, MD, PhD, Study chair, Aarhus University HospitalKim Munk, MD, PhD, Study chair, Aarhus University HospitalHenrik Nissen, MD, PhD, Study chair, Odense University HospitalHelle Andersen, MD, Study chair, Odense University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04084132
- Sponsor's protocol ID
- VD-2018-512
- Status last verified
- Sep 2019
- First submitted
- 25 Feb 2019
- Last updated
- 10 Sep 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04084132
- Acronym / sponsor ID
- VD-2018-512
- Conditions
- Tetralogy of Fallot, Pulmonary Regurgitation
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Copenhagen University Hospital, RigshospitaletUniversity, hospital or other
- Collaborators
- Aarhus University Hospital, Odense University Hospital
- Study start
- 1 Apr 2019 (actual)
- Primary completion
- 31 Dec 2024 (estimated)
- Study completion
- 31 Dec 2031 (estimated)
- First posted
- 10 Sep 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Early re-valving | Experimental | Procedure: Pulmonary valve replacement60 patients who are assigned to early re-valving undergo pulmonary valve replacement within 3 months from randomization. |
| Later re-valving | Experimental | Procedure: Pulmonary valve replacement60 patients who are assigned to later re-valving undergo pulmonary valve replacement when the current European guideline criteria are met. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (13 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pulmonary valve replacementSurgical implantation of an adult-sized (≥ 18 mm) homograft or Contegra graft as right ventricle-to-pulmonary artery conduit under cardiopulmonary bypass through a sternotomy. | Procedure or surgery | Early re-valving, Later re-valving |
Primary outcome
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.
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.
20 secondary outcomes
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
Mean health-associated quality of life (children)
Time frame: 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
Time frame: Assessed once every year for 10 years after randomization
Mean peak oxygen consumption during cardiopulmonary exercise testing
Time frame: Assessed once every year for 10 years after randomization
Median time until structural valve deterioration in patients who are re-valved during the study
Time frame: 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
Time frame: 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
Time frame: Assessed once every year for 10 years after randomization
Mean number of contacts to the health system
Time frame: Assessed once every year for 10 years after randomization
Mean number of children for female patients
Time frame: Assessed once every year for 10 years after randomization
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2019.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Lars Søndergaard, MD, DMSc principal investigator
Copenhagen University Hospital, Rigshospitalet
Morten H Smerup, MD, PhD study chair
Copenhagen University Hospital, Rigshospitalet
Dorte G Nielsen, MD, PhD study chair
Aarhus University Hospital
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Pulmonary valve replacement in people with Tetralogy of Fallot and Pulmonary Regurgitation, run by Copenhagen University Hospital, Rigshospitalet at 3 sites in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 10 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mathis Gröning, MD, DMSc (+45 42404489, mathis.groening@regionh.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean right ventricular end-diastolic volume indexed to body surface area (time frame: 3 years after randomization). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2019.