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Tetralogy of FallotPhase 3NCT00564993

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

A Phase 3 study testing Dobutamin in people with Tetralogy of Fallot, run by Competence Network for Congenital Heart Defects at 11 sites in Germany.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 14 years and older
Conditions the study is for
Tetralogy of Fallot
What is being tested?
Dobutamin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
53 participants
Where
11 sitesGermany
Study dates
Nov 2007to May 2012
Phase
Phase 3
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 14 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 26Show fewer
  • 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

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

Germany11 sites
  • Herz-und Diabeteszentrum Nordrhein-Westfalen

    Bad Oeynhausen, North Rhine-Westphalia, D-32545

  • Deutsches Herzzentrum Berlin

    Berlin, State of Berlin, D-13353

  • Universitätsklinikum Freiburg, Klinik III Päd. Kardiologie

    Freiburg im Breisgau, Baden-Wurttemberg, D-79106

  • Medizinische Hochschule Hannover, Pädiatrische Kardiologie und Intensivmedizin

    Hanover, Lower Saxony, D-30625

  • Universitätsklinikum des Saarlandes

    Homburg/Saar, Saarland, D-66421

  • Universitätsklinikum Schleswig-Holstein Campus Kiel

    Kiel, Schleswig-Holstein, D-24105

  • Herzzentrum Leipzig, Klinik für Kinderkardiologie

    Leipzig, Saxony, D-04289

  • Deutsches Herzzentrum München

    Munich, Bavaria, D-80336

  • Universitätsklinikum Münster, Klinik und Poliklinik für Kinder- und Jugendmedizin, Pädiatrische Kardiologie

    Münster, North Rhine-Westphalia, D-48149

  • Deutsches Kinderherzzentrum St. Augustin

    Sankt Augustin, North Rhine-Westphalia, D-53757

  • Universitätsklinikum Tübingen, Klinik für Kinderheilkunde und Jugendmedizin

    Tübingen, Baden-Wurttemberg, D-72076

Other trials in Germany

About this study

Official title: Cardiac Imaging Under Exercise Stress Test for Early Assessment of Right Ventricular Function in Patients With Tetralogy of Fallot and Pulmonary Regurgitation

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.

Read the 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.

Being tested
Dobutamin
Medical subject headings
Tetralogy of Fallot

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DobutaminDrug

    10\&20 µg/kg/min

Study groups in NCT00564993
Study groupRoleWhat they receive
AActive comparatornecessary 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
Receives: Drug: Dobutamin
BActive comparatorcomparison 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)
Receives: Drug: Dobutamin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Identification of predictive parameters of right ventricular insufficiency

    Measured: 1 year

Secondary outcomes (1)
  1. Evaluation of mortality, morbidity, pulmonary function, objective exercise tolerance, life-quality and prevalence of cardiac arrhythmia after pulmonary valve replacement

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Nov 2007 (estimated)
  2. Study startNov 2007
  3. Primary completionMay 2011
  4. Study completionMay 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Diagnosis
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
53 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00564993
Sponsor's protocol ID
MP 4.3 Fallot-stress
Other IDs
EudraCT number: 2007-003461-41
Status last verified
Aug 2011
First submitted
28 Nov 2007
Last updated
6 Jun 2012
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Dobutamin in people with Tetralogy of Fallot, run by Competence Network for Congenital Heart Defects at 11 sites in Germany.

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 5 inclusion and 26 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: stopped early, as of the sponsor's last update on 6 Jun 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in Germany. 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.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early. Results are not available in the source record.

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?

Identification of predictive parameters of right ventricular insufficiency (time frame: 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 6 Jun 2012.

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