Tetralogy of Fallot for Life

NCT ID: NCT02968264

Last Updated: 2022-12-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

1108 participants

Study Classification

OBSERVATIONAL

Study Start Date

2015-06-08

Study Completion Date

2022-07-01

Brief Summary

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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

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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

Conditions

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Tetralogy of Fallot Congenital Heart Disease Congenital Heart Defect

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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TOF participants

Tetralogy of fallot patients at any age

No interventions assigned to this group

Eligibility Criteria

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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
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The Hospital for Sick Children

OTHER

Sponsor Role collaborator

Population Health Research Institute

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Glen Van Arsdell, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, Los Angeles

Richard Whitlock, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Population Health Research Institute

Locations

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Nemours Children's Hospital

Orlando, Florida, United States

Site Status

Morgan Stanley Children's Hospital

New York, New York, United States

Site Status

Royal Children's Hospital

Parkville, Victoria, Australia

Site Status

Hospital for Sick Children

Toronto, Ontario, Canada

Site Status

West China Hospital

Chengdu, Sichuan, China

Site Status

Beijing Fuwai Hospital

Beijing, , China

Site Status

Guangzhou Women and Children's Medical Center

Guangdong, , China

Site Status

Guangdong Cardiovascular Institute

Guangdong, , China

Site Status

Shanghai Children's Medical Centre

Shanghai, , China

Site Status

Shanghai Xinhua Hospital

Shanghai, , China

Site Status

Fortis Escorts Heart Institute

New Delhi, National Capital Territory of Delhi, India

Site Status

Kokilaben Dhirubhai Ambani Hospital & Medical Research Institutev

Mumbai, , India

Site Status

National Cardiovascular Center Harapan Kita

Jakarta, , Indonesia

Site Status

Okayama University Hospital

Okayama, , Japan

Site Status

Manmohan Cardiothoracic Vascular and Transplant Center

Kathmandu, , Nepal

Site Status

Academician E.N. Meshalkin Research

Novosibirsk, , Russia

Site Status

King Abdulaziz University Hospital

Jeddah, Mecca Region, Saudi Arabia

Site Status

King Faisal Specialist Hospital and Research Centre - Jeddah

Jeddah, , Saudi Arabia

Site Status

Asan Medical Center

Seoul, , South Korea

Site Status

Children's Cardiac Center - Ukraine

Kyiv, , Ukraine

Site Status

Countries

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United States Australia Canada China India Indonesia Japan Nepal Russia Saudi Arabia South Korea Ukraine

References

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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.

Reference Type BACKGROUND
PMID: 23087090 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20732501 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11041398 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24513776 (View on PubMed)

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.

Reference Type BACKGROUND

Other Identifiers

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TOF-LIFE 2.0 2015-06-11

Identifier Type: -

Identifier Source: org_study_id