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Cardiac Function Under Stress for Early Detection of the Right Ventricular Insufficiency After Repair of Tetralogy of Fallot

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ClinicalTrials.gov Identifier: NCT00564993
Recruitment Status : Terminated
First Posted : November 29, 2007
Last Update Posted : June 6, 2012
Sponsor:
Collaborator:
German Federal Ministry of Education and Research
Information provided by:
Competence Network for Congenital Heart Defects

Tracking Information
First Submitted Date  ICMJE November 28, 2007
First Posted Date  ICMJE November 29, 2007
Last Update Posted Date June 6, 2012
Study Start Date  ICMJE November 2007
Actual Primary Completion Date May 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 28, 2007)
Identification of predictive parameters of right ventricular insufficiency [ Time Frame: 1 year ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 28, 2007)
Evaluation of mortality, morbidity, pulmonary function, objective exercise tolerance, life-quality and prevalence of cardiac arrhythmia after pulmonary valve replacement [ Time Frame: 1 year ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Cardiac Function Under Stress for Early Detection of the Right Ventricular Insufficiency After Repair of Tetralogy of Fallot
Official Title  ICMJE Cardiac Imaging Under Exercise Stress Test for Early Assessment of Right Ventricular Function in Patients With Tetralogy of Fallot and Pulmonary Regurgitation
Brief Summary

Summary:

The investigators aim to identify markers of right ventricular dysfunction in patients with severe pulmonary regurgitation following repair of Tetralogy of Fallot, that allow prediction of the optimal timing of the replacement of the regurgitant valve. The investigators will use MR as a gold-standard reference for measurement of cardiac function during rest and dobutamine stress. The investigators will also evaluate the predictive potential of tissue Doppler imaging in this patient group.

Purpose:

To predict the optimum timing of pulmonary valve replacement for severe regurgitation in repaired Tetralogy of Fallot using Cardiac Magnetic resonance with dobutamine stress testing.

Detailed Description

Tetralogy of Fallot (ToF) is the single commonest complex cardiac condition. It consists of ventricular septal defect (VSD), overriding of the aorta in association with the VSD, pulmonary stenosis and right ventricular (RV) hypertrophy. Surgical repair is indicated as it significantly improves life-expectancy. The results of surgical repair have improved steadily over the last 40 years resulting in a significant population surviving into young adulthood. However, standard repair techniques induce regurgitation of the pulmonary valve due to relief of the right ventricular outflow tract obstruction. Over time this regurgitation induces right ventricular dilatation and dysfunction. RV dilatation and dysfunction correlate with reduced exercise tolerance, arrhythmias, and sudden death following repair.

Replacement of the pulmonary valve, late after primary repair of ToF, has generally been shown to improve symptoms as measured by NYHA classification as it improves haemodynamics, exercise tolerance and dysrhythmia. Though generally safe, surgical replacement of the pulmonary valve exposes the patient to cardio-pulmonary by-pass, which may have detrimental effects on both the myocardium and the brain. Furthermore transplanted valves of various types have a limited life span and thus early repair of the pulmonary valve may instigate a series of re-operations, which will recur throughout the patient's life exposing them to a cumulative risk of morbidity and mortality. Unfortunately there is evidence in the literature that symptomatic improvement is reduced if pulmonary valve replacement is delayed for too long. This is probably due to irreversible myocardial damage with little remodeling of the RV despite a competent pulmonary valve.

In the light of these two opposing factors; potential for failure to recover and avoiding multiple operations there is a need to establish preoperative markers which will allow identification of the failing ventricle before it passes the point of recovery. This will allow close follow-up with intervention timed to minimize loss of function whilst taking into account the likely need for re-operation.

However, it is still unclear, which criteria give the best indication for the need of re-interventions. Two other studies of the Competence Network for Congenital Heart Defects ("Follow up of Post-Repair Tetralogy of Fallot (HP 4.1)" and "Early re-intervention in infants and small children after correction of Tetralogy of Fallot: Prospective analysis of myocardial benefit using cardiac MRI and echocardiography (HP 4.2)" analyze the benefit of such re-interventions and will hopefully provide substantive information on timing of PVR.

There are however references in literature that cardiac imaging procedure under stress possibly results in more sensitive predictive parameters of right ventricular insufficiency than conducted under rest. Dobutamine stress testing has a long history of safe and clinically useful application in ischemic cardiomyopathy and recent studies have demonstrated it's useful predictive value in various outcomes for non-ischemic cardiomyopathy.

Accurate post-operative characterization will allow identification of pre-operative predictive markers. The investigators believe that dobutamine stress testing may in fact be an excellent predictive marker. Dobutamine increases intrinsic contractability as well as reducing after load. It is thought that the failing heart is not able to positively respond to the dobutamine stimulus, and dobutamine stress will thus demonstrate evidence of irreversible damage. Identification of predictive markers of the point at which irreversible myocardial damage occurs will allow better timing of pulmonary valve replacement and will have significant ramifications for the management of this patient group.

In this study imaging procedures (MRI and echocardiography) under rest and stress (dobutamine) are compared before and after pulmonary valve replacement at severe pulmonary insufficiency after repair of Tetralogy of Fallot, whereas the imaging procedure of echocardiography under stress is optional. The data obtained are supposed to determine new parameters of the early right ventricular insufficiency. The investigators will correlate the above objective data with subjective data of change in symptoms and exercise capacity pre- and post-repair. Fallot patients with a good result of repair and good right ventricular function will serve as a comparison group.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Condition  ICMJE Tetralogy of Fallot
Intervention  ICMJE Drug: Dobutamin
10&20 µg/kg/min
Study Arms  ICMJE
  • Active Comparator: A

    necessary re-intervention (pulmonary valve replacement) after repair of Fallot:

    2 Visits with cardiac imaging under rest and stress (Dobutamin) before and after pulmonary valve replacement

    Intervention: Drug: Dobutamin
  • Active Comparator: B

    comparison group: with a good result of repair of tetralogy of fallot and good ventricular function:

    1 Visit with cardiac imaging under rest and stress (Dobutamin)

    Intervention: Drug: Dobutamin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: June 5, 2012)
53
Original Estimated Enrollment  ICMJE
 (submitted: November 28, 2007)
80
Actual Study Completion Date  ICMJE May 2012
Actual Primary Completion Date May 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Written informed consent of the patient or patient's legal representatives
  • No participation in another AMG driven study within the past 4 weeks or during the whole duration of this study
  • Patients with Tetralogy of Fallot after corrective surgery

    • group A (n=45): Adolescents ≥ 14 years or adults with Tetralogy of Fallot after corrective surgery and necessary re-intervention (pulmonary valve replacement because of pulmonary insufficiency
    • group B (n=35): Adolescents ≥ 14 years or adults with Tetralogy of Fallot after corrective surgery and good result of repair and good right ventricular function

Exclusion Criteria:

Non-specific

  • pregnancy or lactation
  • women of child-bearing age who are sexually active without practising highly effective methods of contraception (a urine/serum pregnancy test may be requested at the discretion of the investigator)
  • any diseases or impairment that, in the opinion of the investigator, would justify to exclude a subject from participation
  • substance abuse (alcohol, medicines, drugs)
  • other medical, psychological or social circumstances that would adversely affect a patient's ability to participate reliably in the study or increase the risk to themselves or others if they participated
  • insufficient compliance
  • disagreement with storage & transfer of anonymized disease data within this study.
  • Persons who are detained officially or legally to an official institution

Specific

  • contraindication against pharmacological stress testing (ventricular tachycardia or severe arrhythmia, profound pulmonary stenosis and hypertension of the pulmonary artery)
  • coronary heart disease
  • atrial fibrillation or flutter
  • DORV (if there is another VSD than subaortic)
  • associated severe heart defects
  • associated other severe (=hemodynamic significantly) valvular defects except for pulmonary insufficiency
  • Other clinically relevant diseases, such as malignant tumour or florid diseases (as considered by the investigating physician)
  • MRI contraindication, e.g. cardiac pacemaker, implanted neurostimulators and other magnetisable foreign bodies
  • Patient is not able to perform spiroergometry (bicycle/treadmill) or existing contraindications
  • Patients with Type I or II diabetes
  • prohibited concomitant medication: MAO-inhibitors
  • Treatment with beta- or alpha-blocker
  • Treatment with high doses of ACE-inhibitors or inhibitors of the AT- receptor and permanent treatment with nitrates (in the investigating physician's risk assessment)
  • Anticoagulation treatment (risk-benefit decision by the investigating physician, as there may be additional inhibition of platelet aggregation with dobutamine)
  • Treatment with diuretics (risk-benefit decision by the investigating physician, as there may be enhancement of the hypokalemia by administration of dobutamine); if necessary verification of the serum K+ -level before exposure to dobutamine
  • all contraindications against the study medication described in the SMPC
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 14 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00564993
Other Study ID Numbers  ICMJE MP 4.3 Fallot-stress
EudraCT number: 2007-003461-41
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Not Provided
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Competence Network for Congenital Heart Defects
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE German Federal Ministry of Education and Research
Investigators  ICMJE
Study Chair: Philipp Beerbaum, MD Evelina Children's Hospital, Guy's and St. Thomas Foundation Trust, Interdisciplinary Medical Imaging Group, King's College London
PRS Account Competence Network for Congenital Heart Defects
Verification Date August 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP