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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02968264
Other study ID # TOF-LIFE 2.0 2015-06-11
Secondary ID
Status Completed
Phase
First received
Last updated
Start date June 8, 2015
Est. completion date July 1, 2022

Study information

Verified date December 2022
Source Population Health Research Institute
Contact n/a
Is FDA regulated No
Health authority
Study type Observational [Patient Registry]

Clinical 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 practices.


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 1. 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. 2. Retrospective registry data published by STS and EACTS omit many crucial surgical and clinical variables that can potentially impact outcomes. 3. None of the current evidence are based on anatomically matched/adjusted patients


Recruitment information / eligibility

Status Completed
Enrollment 1108
Est. completion date July 1, 2022
Est. primary completion date March 15, 2022
Accepts healthy volunteers No
Gender All
Age group N/A and older
Eligibility Inclusion Criteria: - 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 Exclusion Criteria: - 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 - 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

Study Design


Locations

Country Name City State
Australia Royal Children's Hospital Parkville Victoria
Canada Hospital for Sick Children Toronto Ontario
China Beijing Fuwai Hospital Beijing
China West China Hospital Chengdu Sichuan
China Guangdong Cardiovascular Institute Guangdong
China Guangzhou Women and Children's Medical Center Guangdong
China Shanghai Children's Medical Centre Shanghai
China Shanghai Xinhua Hospital Shanghai
India Kokilaben Dhirubhai Ambani Hospital & Medical Research Institutev Mumbai
India Fortis Escorts Heart Institute New Delhi Delhi
Indonesia National Cardiovascular Center Harapan Kita Jakarta
Japan Okayama University Hospital Okayama
Korea, Republic of Asan Medical Center Seoul
Nepal Manmohan Cardiothoracic Vascular and Transplant Center Kathmandu
Russian Federation Academician E.N. Meshalkin Research Novosibirsk
Saudi Arabia King Abdulaziz University Hospital Jeddah Makkah
Saudi Arabia King Faisal Specialist Hospital and Research Centre - Jeddah Jeddah
Ukraine Children's Cardiac Center - Ukraine Kyiv
United States Morgan Stanley Children's Hospital New York New York
United States Nemours Children's Hospital Orlando Florida

Sponsors (2)

Lead Sponsor Collaborator
Population Health Research Institute The Hospital for Sick Children

Countries where clinical trial is conducted

United States,  Australia,  Canada,  China,  India,  Indonesia,  Japan,  Korea, Republic of,  Nepal,  Russian Federation,  Saudi Arabia,  Ukraine, 

References & Publications (5)

Al 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. — View Citation

d'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. — View Citation

Gatzoulis 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. — View Citation

Pondorfer 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.

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. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary 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. 2 years post-repair
Secondary 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. 2 years
Secondary Cardiovascular mortality rate To determine the 30-day and 2 year cardiovascular mortality rate (for equivalent patients) after primary and staged repair. 30 days and 2 years after repair
Secondary Rate of palliation failure To determine the rate of palliation failure following various palliation techniques 2 years
Secondary 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. 2 years
Secondary 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. 2 years
Secondary 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) 2 years
Secondary 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. 2 years
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