Tetralogy of FallotTOF-LIFENCT02968264
Tetralogy of Fallot for Life
An observational study of Tetralogy of Fallot and Congenital Heart Disease, run by Population Health Research Institute at 20 sites in 12 countries.
Trial summary
The aim is to conduct a prospective multi-centre international inception cohort study with an enrollment goal of 3,000 TOF patients and 2 year follow-up post-repair. The proposed sample size and methodology will result in statistically powerful results to allow for evidence-based change to current TOF surgical… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Tetralogy of Fallot, Congenital Heart Disease, Congenital Heart Defect
- How many people
- 1,108 participants
- Where
- 20 sitesin 12 countries
- Study dates
- 8 Jun 2015to 1 Jul 2022
- How long will I take part?
- 2 Years
- Phase
- Observational
- Are there results?
- None posted in the registry
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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: TOF patients of any age undergoing their first cardiac intervention. Please refer to the eligibility criteria for more details.
Who may be able to join
- TOF with RVOT stenosis. TOF is defined as anterio-cephalad deviation of the ventricular outlet septum with no more than 50% aortic override and a single outflow VSD.
- TOF with pulmonary atresia and confluent pulmonary arteries.
- Admitted with intent to treat (i.e. patient planned to undergo a primary or staged repair).
- Patients with coronary artery anomalies, right aortic arch, and 22q11 deletion may be included
Who cannot join
- TOF with absent pulmonary valve
- Other major cardiac anomalies such as AVSD, multiple VSDs, right atrial isomerism, and MAPCAs. In this instance, the definition of MAPCAs does not include dilated bronchial collateral arteries.
- Unbalanced ventricles precluding biventricular repair
- Major genetic abnormalities/syndromes e.g. trisomy 13,18, and 21
- Major extra cardiac anomalies e.g. diaphragmatic hernia, omphalocele, absent sternum, cerebral palsy
- Infective endocarditis as an indication for intra-cardiac repair
Show all 10Show fewer
- Stroke in the last 30 days prior to palliation or intra-cardiac repair
- Known diagnosis of HIV or hepatitis B
- Any previous cardiac procedures
- Patient's circumstance that precludes completion of follow-up telephone call and/or obtaining information from the 2-year cardiology follow-up
Trial locations and contacts
20 sites in 12 countries.
20 sites in 12 countries
China6 sites
Beijing Fuwai Hospital
Beijing, 100037
West China Hospital
Chengdu, Sichuan, 610041
Guangzhou Women and Children's Medical Center
Guangdong, 510623
Guangdong Cardiovascular Institute
Guangdong
Shanghai Children's Medical Centre
Shanghai
Shanghai Xinhua Hospital
Shanghai
United States2 sites
Morgan Stanley Children's Hospital
New York, New York, 10032
Nemours Children's Hospital
Orlando, Florida, 32827
India2 sites
Kokilaben Dhirubhai Ambani Hospital & Medical Research Institutev
Mumbai, 400 053
Fortis Escorts Heart Institute
New Delhi, National Capital Territory of Delhi, 110025
Saudi Arabia2 sites
King Abdulaziz University Hospital
Jeddah, Mecca Region, 21589
King Faisal Specialist Hospital and Research Centre - Jeddah
Jeddah, 21499
Nepal1 site
Manmohan Cardiothoracic Vascular and Transplant Center
Kathmandu, 977
About this study
The aim is to conduct a prospective multi-centre international inception cohort study with an enrollment goal of 3,000 TOF patients and 2 year follow-up post-repair. The proposed sample size and methodology will result in statistically powerful results to allow for evidence-based change to current TOF surgical practices.
Read the detailed description
Background: Tetralogy of Fallot (TOF) is the most common cyanotic heart defect consisting of 7-10% of all congenital heart disease with an estimated annual global incidence rate of 38,000. It is fatal if untreated; only 50% of patients are alive at 1 year of age. Surgery has dramatically improved the survival so that >95% of repaired TOF children are alive by one year. The initial justified enthusiasm for the benefit of surgical therapy are now tempered by the findings of late sudden cardiac death secondary to right ventricular (RV) dysfunction. The original trans-ventricular/trans-annular patching repair results in significant pulmonary insufficiency which leads to RV dilation, subsequent functional tricuspid regurgitation, atrial arrhythmias, and eventual RV failure and ventricular arrhythmias. In attempt to break this cycle, an increasing number of patients are undergoing late pulmonary valve implantation.
Recognizing that the RV adapts to stress signals has led to the idea that leaving mixed residual stenosis and regurgitation may yield to an adaptive change that limits RV dilation while still allowing for adequate cardiac output. Early attempts to limit pulmonary insufficiency and RV damage involve minimal trans-annular patching or complete annulus preservation (AP). Emerging data suggest that patients with a mixed lesion have improved survival, so that 96.6% are alive at 25-years in comparison to 85-90% survival for the conventional technique.
Preliminary Data: A review of data comparing AP to TAP repair at our institution (n=185, AP repair=124, TAP=61) demonstrated that at 10-15 year follow-up those who received an AP repair had smaller RV volumes and pulmonary regurgitant jet width. They were also seen to have improved exercise capacity as measure by VO2 max tests. The AP technique also has been seen to significantly decrease the risk of reoperation in comparison to TAP, 11% and 29% respectively.
Current Problem: Although trans-ventricular VSD closure along with a TAP is known to result in increased risk of long-term morbidity and mortality, it continues to be the predominant repair strategy implemented globally according to STS/EACTS databases. Reasons for this are:
- Trans-ventricular/TAP approach is technically easier than annulus preservation, which often requires multiple pump runs
- There is a fear of leaving too much obstruction
- High quality evidence supporting one approach over the other is lacking.
Gaps in Literature
- Most data on the impact of surgical strategy emerge from single centre experiences that are retrospective and based on small patient population. This makes the results difficult to standardize to the general TOF population.
- Retrospective registry data published by STS and EACTS omit many crucial surgical and clinical variables that can potentially impact outcomes.
- None of the current evidence are based on anatomically matched/adjusted patients
- Medical subject headings
- Tetralogy of Fallot, Heart Defects, Congenital
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| TOF participants | Tetralogy of fallot patients at any age |
What is being measured
The primary outcome is the main question the study is designed to answer.
RV physiology and morphology
To determine the association between baseline morphology, surgical repair technique (various surgical strategies for VSD closure and managing the RVOT), and RV physiology and morphology at 2 years obtained from echocardiogram studies.
Measured: 2 years post-repair
Secondary outcomes (7)
Number of patients undergoing various palliation procedures and surgical repair strategies
To determine the pattern of palliation procedures (BT shunt, RVOT stent, or balloon dilation), surgical repair strategy (staged versus primary repair), and surgical repair technique (AP, minimal TAP, standard TAP) at participating centres.
Measured: 2 years
Cardiovascular mortality rate
To determine the 30-day and 2 year cardiovascular mortality rate (for equivalent patients) after primary and staged repair.
Measured: 30 days and 2 years after repair
Rate of palliation failure
To determine the rate of palliation failure following various palliation techniques
Measured: 2 years
Effect of palliation procedures on cardiac morphology
To determine the possible effect of palliative procedures (BT shunts, balloon dilation, stent insertion) on cardiac morphology (growth of the infundibular chamber, the pulmonary annulus and PA branches' diameter) and subsequent repair technique.
Measured: 2 years
Post-operative restrictive physiology
To determine the relationship between repair technique/strategy and prevalence of postoperative restrictive physiology as defined by the presence of antegrade flow in pulmonary artery during atrial contraction on echocardiogram.
Measured: 2 years
Cardiac re-interventions
To determine the relationship between TOF repair strategy/technique on the incidence and prevalence of cardiac re-interventions (e.g. pulmonary valve implantation, RVOT stent insertion or balloon dilatation)
Measured: 2 years
RV physiology and morphology following TOF pulmonary atresia repair
To determine the right ventricular morphological and physiological adaptations to severe pulmonary stenosis or regurgitation using repaired TOF pulmonary atresia as a model. For example RV/LV end diastolic and systolic diameter ratio. RV and LV wall thickness relation to outflow gradient obtained by echocardiogram studies.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2016 (estimated)
- Study start8 Jun 2015
- Primary completion15 Mar 2022
- Study completion1 Jul 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Tetralogy of FallotStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 1,108 participants (actual)
- Target duration
- 2 Years
Sponsor and investigators
- Lead sponsor
- Population Health Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- The Hospital for Sick Children
- Responsible party
- Sponsor
- Investigators
- Glen Van Arsdell, MD, Principal investigator, University of California, Los AngelesRichard Whitlock, MD, PhD, Principal investigator, Population Health Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02968264
- Sponsor's protocol ID
- TOF-LIFE 2.0 2015-06-11
- Acronym
- TOF-LIFE
- Status last verified
- Dec 2022
- First submitted
- 4 Jan 2016
- Last updated
- 21 Dec 2022
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Sarris GE, Comas JV, Tobota Z, Maruszewski B. Results of reparative surgery for tetralogy of Fallot: data from the European Association for Cardio-Thoracic Surgery Congenital Database. Eur J Cardiothorac Surg. 2012 Nov;42(5):766-74; discussion 774. doi: 10.1093/ejcts/ezs478.
PubMed 23087090Al Habib HF, Jacobs JP, Mavroudis C, Tchervenkov CI, O'Brien SM, Mohammadi S, Jacobs ML. Contemporary patterns of management of tetralogy of Fallot: data from the Society of Thoracic Surgeons Database. Ann Thorac Surg. 2010 Sep;90(3):813-9; discussion 819-20. doi: 10.1016/j.athoracsur.2010.03.110.
PubMed 20732501Gatzoulis MA, Balaji S, Webber SA, Siu SC, Hokanson JS, Poile C, Rosenthal M, Nakazawa M, Moller JH, Gillette PC, Webb GD, Redington AN. Risk factors for arrhythmia and sudden cardiac death late after repair of tetralogy of Fallot: a multicentre study. Lancet. 2000 Sep 16;356(9234):975-81. doi: 10.1016/S0140-6736(00)02714-8.
PubMed 11041398d'Udekem Y, Galati JC, Rolley GJ, Konstantinov IE, Weintraub RG, Grigg L, Ramsay JM, Wheaton GR, Hope S, Cheung MH, Brizard CP. Low risk of pulmonary valve implantation after a policy of transatrial repair of tetralogy of Fallot delayed beyond the neonatal period: the Melbourne experience over 25 years. J Am Coll Cardiol. 2014 Feb 18;63(6):563-8. doi: 10.1016/j.jacc.2013.10.011. Epub 2013 Oct 30.
PubMed 24513776Pondorfer P YT, Cheung M, Ashburn D, Manlhiot C, McCrindle B, Mertens L, Grosse-Wortmann L, Redington A, Van Arsdell G. Abstract 18833: Annulus Preservation Strategy Improves Late Outcomes in Tetralogy of Fallot: An Anatomical Equivalency Study. Circulation. 2014;130:A18833.
Study at a glance
From the registry record, last updated by the sponsor on 21 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tetralogy of Fallot for Life
- ClinicalTrials.gov ID
- NCT02968264
- Acronym / sponsor ID
- TOF-LIFE / TOF-LIFE 2.0 2015-06-11
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 1,108 participants (actual)
- Lead sponsor
- Population Health Research InstituteUniversity, hospital or other
- Collaborators
- The Hospital for Sick Children
- Study start
- 8 Jun 2015 (actual)
- Primary completion
- 15 Mar 2022 (actual)
- Study completion
- 1 Jul 2022 (actual)
- First posted
- 18 Nov 2016 (estimated)
- 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.
The aim is to conduct a prospective multi-centre international inception cohort study with an enrollment goal of 3,000 TOF patients and 2 year follow-up post-repair. The proposed sample size and methodology will result in statistically powerful results to allow for evidence-based change to current TOF surgical practices.
Detailed description
Background: Tetralogy of Fallot (TOF) is the most common cyanotic heart defect consisting of 7-10% of all congenital heart disease with an estimated annual global incidence rate of 38,000. It is fatal if untreated; only 50% of patients are alive at 1 year of age. Surgery has dramatically improved the survival so that >95% of repaired TOF children are alive by one year. The initial justified enthusiasm for the benefit of surgical therapy are now tempered by the findings of late sudden cardiac death secondary to right ventricular (RV) dysfunction. The original trans-ventricular/trans-annular patching repair results in significant pulmonary insufficiency which leads to RV dilation, subsequent functional tricuspid regurgitation, atrial arrhythmias, and eventual RV failure and ventricular arrhythmias. In attempt to break this cycle, an increasing number of patients are undergoing late pulmonary valve implantation.
Recognizing that the RV adapts to stress signals has led to the idea that leaving mixed residual stenosis and regurgitation may yield to an adaptive change that limits RV dilation while still allowing for adequate cardiac output. Early attempts to limit pulmonary insufficiency and RV damage involve minimal trans-annular patching or complete annulus preservation (AP). Emerging data suggest that patients with a mixed lesion have improved survival, so that 96.6% are alive at 25-years in comparison to 85-90% survival for the conventional technique.
Preliminary Data: A review of data comparing AP to TAP repair at our institution (n=185, AP repair=124, TAP=61) demonstrated that at 10-15 year follow-up those who received an AP repair had smaller RV volumes and pulmonary regurgitant jet width. They were also seen to have improved exercise capacity as measure by VO2 max tests. The AP technique also has been seen to significantly decrease the risk of reoperation in comparison to TAP, 11% and 29% respectively.
Current Problem: Although trans-ventricular VSD closure along with a TAP is known to result in increased risk of long-term morbidity and mortality, it continues to be the predominant repair strategy implemented globally according to STS/EACTS databases. Reasons for this are:
- Trans-ventricular/TAP approach is technically easier than annulus preservation, which often requires multiple pump runs
- There is a fear of leaving too much obstruction
- High quality evidence supporting one approach over the other is lacking.
Gaps in Literature
- Most data on the impact of surgical strategy emerge from single centre experiences that are retrospective and based on small patient population. This makes the results difficult to standardize to the general TOF population.
- Retrospective registry data published by STS and EACTS omit many crucial surgical and clinical variables that can potentially impact outcomes.
- None of the current evidence are based on anatomically matched/adjusted patients
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 2 Years
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TOF participants | – | –Tetralogy of fallot patients at any age |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- TOF patients of any age undergoing their first cardiac intervention. Please refer to the eligibility criteria for more details.
Key inclusion criteria (4 listed)
- TOF with RVOT stenosis. TOF is defined as anterio-cephalad deviation of the ventricular outlet septum with no more than 50% aortic override and a single outflow VSD.
- TOF with pulmonary atresia and confluent pulmonary arteries.
- Admitted with intent to treat (i.e. patient planned to undergo a primary or staged repair).
- Patients with coronary artery anomalies, right aortic arch, and 22q11 deletion may be included
Key exclusion criteria (10 listed)
- TOF with absent pulmonary valve
- Other major cardiac anomalies such as AVSD, multiple VSDs, right atrial isomerism, and MAPCAs. In this instance, the definition of MAPCAs does not include dilated bronchial collateral arteries.
- Unbalanced ventricles precluding biventricular repair
- Major genetic abnormalities/syndromes e.g. trisomy 13,18, and 21
- Major extra cardiac anomalies e.g. diaphragmatic hernia, omphalocele, absent sternum, cerebral palsy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
RV physiology and morphology
Time frame: 2 years post-repair
To determine the association between baseline morphology, surgical repair technique (various surgical strategies for VSD closure and managing the RVOT), and RV physiology and morphology at 2 years obtained from echocardiogram studies.
7 secondary outcomes
Number of patients undergoing various palliation procedures and surgical repair strategies
Time frame: 2 years
Cardiovascular mortality rate
Time frame: 30 days and 2 years after repair
Rate of palliation failure
Time frame: 2 years
Effect of palliation procedures on cardiac morphology
Time frame: 2 years
Post-operative restrictive physiology
Time frame: 2 years
Cardiac re-interventions
Time frame: 2 years
RV physiology and morphology following TOF pulmonary atresia repair
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Dec 2022.
- Background: PubMed 23087090Sarris GE, Comas JV, Tobota Z, Maruszewski B. Results of reparative surgery for tetralogy of Fallot: data from the European Association for Cardio-Thoracic Surgery Congenital Database. Eur J Cardiothorac Surg. 2012 Nov;42(5):766-74; discussion 774. doi: 10.1093/ejcts/ezs478.
- Background: PubMed 20732501Al Habib HF, Jacobs JP, Mavroudis C, Tchervenkov CI, O'Brien SM, Mohammadi S, Jacobs ML. Contemporary patterns of management of tetralogy of Fallot: data from the Society of Thoracic Surgeons Database. Ann Thorac Surg. 2010 Sep;90(3):813-9; discussion 819-20. doi: 10.1016/j.athoracsur.2010.03.110.
- Background: PubMed 11041398Gatzoulis MA, Balaji S, Webber SA, Siu SC, Hokanson JS, Poile C, Rosenthal M, Nakazawa M, Moller JH, Gillette PC, Webb GD, Redington AN. Risk factors for arrhythmia and sudden cardiac death late after repair of tetralogy of Fallot: a multicentre study. Lancet. 2000 Sep 16;356(9234):975-81. doi: 10.1016/S0140-6736(00)02714-8.
- Background: PubMed 24513776d'Udekem Y, Galati JC, Rolley GJ, Konstantinov IE, Weintraub RG, Grigg L, Ramsay JM, Wheaton GR, Hope S, Cheung MH, Brizard CP. Low risk of pulmonary valve implantation after a policy of transatrial repair of tetralogy of Fallot delayed beyond the neonatal period: the Melbourne experience over 25 years. J Am Coll Cardiol. 2014 Feb 18;63(6):563-8. doi: 10.1016/j.jacc.2013.10.011. Epub 2013 Oct 30.
- BackgroundPondorfer P YT, Cheung M, Ashburn D, Manlhiot C, McCrindle B, Mertens L, Grosse-Wortmann L, Redington A, Van Arsdell G. Abstract 18833: Annulus Preservation Strategy Improves Late Outcomes in Tetralogy of Fallot: An Anatomical Equivalency Study. Circulation. 2014;130:A18833.
- 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. This study is not recruiting at the moment.
Glen Van Arsdell, MD principal investigator
University of California, Los Angeles
Richard Whitlock, MD, PhD principal investigator
Population Health Research Institute
20 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Tetralogy of Fallot and Congenital Heart Disease, run by Population Health Research Institute at 20 sites in 12 countries.
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 4 inclusion and 10 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: finished, as of the sponsor's last update on 21 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in China, United States, India, Saudi Arabia, Australia and 7 more countries. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
RV physiology and morphology (time frame: 2 years post-repair). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02968264, which also lists 5 linked publications.
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 21 Dec 2022.