Cardiac Function Under Stress for Early Detection of the Right Ventricular Insufficiency After Repair of Tetralogy of Fallot
Primary Purpose
Tetralogy of Fallot
Status
Terminated
Phase
Phase 3
Locations
Germany
Study Type
Interventional
Intervention
Dobutamin
Sponsored by
About this trial
This is an interventional diagnostic trial for Tetralogy of Fallot
Eligibility Criteria
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
Sites / Locations
- Universitätsklinikum Freiburg, Klinik III Päd. Kardiologie
- Universitätsklinikum Tübingen, Klinik für Kinderheilkunde und Jugendmedizin
- Deutsches Herzzentrum München
- Medizinische Hochschule Hannover, Pädiatrische Kardiologie und Intensivmedizin
- Herz-und Diabeteszentrum Nordrhein-Westfalen
- Universitätsklinikum Münster, Klinik und Poliklinik für Kinder- und Jugendmedizin, Pädiatrische Kardiologie
- Deutsches Kinderherzzentrum St. Augustin
- Universitätsklinikum des Saarlandes
- Herzzentrum Leipzig, Klinik für Kinderkardiologie
- Universitätsklinikum Schleswig-Holstein Campus Kiel
- Deutsches Herzzentrum Berlin
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
A
B
Arm Description
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
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)
Outcomes
Primary Outcome Measures
Identification of predictive parameters of right ventricular insufficiency
Secondary Outcome Measures
Evaluation of mortality, morbidity, pulmonary function, objective exercise tolerance, life-quality and prevalence of cardiac arrhythmia after pulmonary valve replacement
Full Information
NCT ID
NCT00564993
First Posted
November 28, 2007
Last Updated
June 5, 2012
Sponsor
Competence Network for Congenital Heart Defects
Collaborators
German Federal Ministry of Education and Research
1. Study Identification
Unique Protocol Identification Number
NCT00564993
Brief Title
Cardiac Function Under Stress for Early Detection of the Right Ventricular Insufficiency After Repair of Tetralogy of Fallot
Official Title
Cardiac Imaging Under Exercise Stress Test for Early Assessment of Right Ventricular Function in Patients With Tetralogy of Fallot and Pulmonary Regurgitation
Study Type
Interventional
2. Study Status
Record Verification Date
August 2011
Overall Recruitment Status
Terminated
Study Start Date
November 2007 (undefined)
Primary Completion Date
May 2011 (Actual)
Study Completion Date
May 2012 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Competence Network for Congenital Heart Defects
Collaborators
German Federal Ministry of Education and Research
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tetralogy of Fallot
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
53 (Actual)
8. Arms, Groups, and Interventions
Arm Title
A
Arm Type
Active Comparator
Arm Description
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
Arm Title
B
Arm Type
Active Comparator
Arm Description
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 Type
Drug
Intervention Name(s)
Dobutamin
Intervention Description
10&20 µg/kg/min
Primary Outcome Measure Information:
Title
Identification of predictive parameters of right ventricular insufficiency
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Evaluation of mortality, morbidity, pulmonary function, objective exercise tolerance, life-quality and prevalence of cardiac arrhythmia after pulmonary valve replacement
Time Frame
1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
14 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Philipp Beerbaum, MD
Organizational Affiliation
Evelina Children's Hospital, Guy's and St. Thomas Foundation Trust, Interdisciplinary Medical Imaging Group, King's College London
Official's Role
Study Chair
Facility Information:
Facility Name
Universitätsklinikum Freiburg, Klinik III Päd. Kardiologie
City
Freiburg
State/Province
Baden-Wuerttemberg
ZIP/Postal Code
D-79106
Country
Germany
Facility Name
Universitätsklinikum Tübingen, Klinik für Kinderheilkunde und Jugendmedizin
City
Tübingen
State/Province
Baden-Wuerttemberg
ZIP/Postal Code
D-72076
Country
Germany
Facility Name
Deutsches Herzzentrum München
City
Munich
State/Province
Bavaria
ZIP/Postal Code
D-80336
Country
Germany
Facility Name
Medizinische Hochschule Hannover, Pädiatrische Kardiologie und Intensivmedizin
City
Hannover
State/Province
Lower Saxony
ZIP/Postal Code
D-30625
Country
Germany
Facility Name
Herz-und Diabeteszentrum Nordrhein-Westfalen
City
Bad Oeynhausen
State/Province
North Rhine-Westphalia
ZIP/Postal Code
D-32545
Country
Germany
Facility Name
Universitätsklinikum Münster, Klinik und Poliklinik für Kinder- und Jugendmedizin, Pädiatrische Kardiologie
City
Münster
State/Province
North Rhine-Westphalia
ZIP/Postal Code
D-48149
Country
Germany
Facility Name
Deutsches Kinderherzzentrum St. Augustin
City
Sankt Augustin
State/Province
North Rhine-Westphalia
ZIP/Postal Code
D-53757
Country
Germany
Facility Name
Universitätsklinikum des Saarlandes
City
Homburg/Saar
State/Province
Saarland
ZIP/Postal Code
D-66421
Country
Germany
Facility Name
Herzzentrum Leipzig, Klinik für Kinderkardiologie
City
Leipzig
State/Province
Saxony
ZIP/Postal Code
D-04289
Country
Germany
Facility Name
Universitätsklinikum Schleswig-Holstein Campus Kiel
City
Kiel
State/Province
Schleswig-Holstein
ZIP/Postal Code
D-24105
Country
Germany
Facility Name
Deutsches Herzzentrum Berlin
City
Berlin
ZIP/Postal Code
D-13353
Country
Germany
12. IPD Sharing Statement
Links:
URL
http://www.kompetenznetz-ahf.de
Description
Competence Network for Congenital Heart Defects
Learn more about this trial
Cardiac Function Under Stress for Early Detection of the Right Ventricular Insufficiency After Repair of Tetralogy of Fallot
We'll reach out to this number within 24 hrs