Trial document

drksid header


Trial Description

start of 1:1-Block title


Effect and Safety of preventive Treatment with ACE-Inhibitor and Beta-Blocker on the onset of Left Ventricular Dysfunction in Duchenne Muscular Dystrophy

end of 1:1-Block title
start of 1:1-Block acronym

Trial Acronym

DMD Kardio

end of 1:1-Block acronym
start of 1:1-Block url

URL of the Trial


end of 1:1-Block url
start of 1:1-Block public summary

Brief Summary in Lay Language

DMD is a lethal disorder of childhood charakterized by progressive muscle wasting caused by mutations (hereditary X-linked) of the dystrophin gene. The defective gene Dystrophin causes an muscle wasting progresses as the patients geting older untill finally respiratory or cardiac failure develops. Prevalence in Germany amount 100 male newborns / year. Nearly all patients with DMD are diagnosed at preschool age and become wheelchair-bound between 13-15 years. Cardiomyopathy develops in the second decade of life resulting in left ventricular dysfunction. Incidence of dilated cardiomyopathy increases with age, up to 57% of DMD patients older than 18 years are suffering under noticeable cardiac insufficiency.

Due to better medical care and home ventilation therapy the life expectancy of DMD-patients has increased in the last three decades, and cardiac failure due to cardiomyopathy increasingly becomes a reason for mortality and morbidity in these patients.

ACE-Inhibitor und Beta-Blocker are established medication used for treatment at cardiac insufficiency mostly at the adult-Patients. The past clinical trials showed already improvement of cardiac dysfunction as also prolongation of Life of Patient who have been taken this medication. There are also a few small studies witch show the same positiv results by children.
It is still an unresolved question if an early prophylactic treatment with a combined ACE-inhibitor/beta-blocker therapy according to modern guidelines in cardiology can delay the onset of left ventricular dysfunction and contribute to a longer survival and better quality of life of DMD patients. A placebo controlled multi-centre trial will assess the effectiveness of preventive treatment with a combination of ACE-inhibitor and beta-blocker.

end of 1:1-Block public summary
start of 1:1-Block scientific synopsis

Brief Summary in Scientific Language

ACE-inhibitors and beta-blockers are used as treatment for heart failure in Duchenne muscular dystrophy. So far, there is only evidence for this drug therapy in cardiomyopathy of other etiology such as dilative cardiomyopathy, alcohol-toxic or ischemic heart disease in adults. Only few studies of low evidence exist suggesting that ACE-inhibitors and beta-blockers are effective in Duchenne cardiomyopathy. This project wants to test the hypothesis that prophylactic anticongestive therapy can delay or avoid manifestation of Duchenne cardiomyopathy.
N=130 patients with Duchenne Muscular with normal left ventricular function (LVSF > =30%) aged 10-14 years will be included into the study and followed in half-yearly intervals for max. 6 years until left ventricular dysfunction (defined by fraction shortening < 28%) becomes apparent. Time to left ventricular dysfunction will be analyzed in a proportional hazards regression model with treatment assignment and study centre as covariates.
History including symptoms, side effects, concomitant medication, intercurrent diseases and quality of life will be documented together with vital parameters and a standard-10-channel-ECG. At each visit, medication will be handed out according to weight class. For efficacy assessment, fraction shortening will be measured by echocardiography. Tissue Doppler Imaging will be used where available as secondary outcome measure. A yearly safety-lab and a 24-h-ECG will check on safety and tolerability, neurohumeral mediators (Noradrenalin, Aldosteron, Angiotensin II, Renin, pro-BNP) will be done three times during the study. In case of positive study results, further studies to confirm therapeutic benefit will follow. Tissue Doppler Imaging will be evaluated in comparison to 2D echocardiography.
According to Amendment 01 of 12. Dec. 2012 the number of patients to be randomised was reduced from 130 to 55 patients and the recruitment period was extended until December 2013.
The extended recruitment period ended on 31. Dec. 2013 with 42 randomised patients.

end of 1:1-Block scientific synopsis
start of 1:1-Block organizational data

Organizational Data

  •   DRKS00000115
  •   2009/11/18
  •   [---]*
  •   yes
  •   Approved
  •   08_2009, Ethik-Kommission der Friedrich-Alexander-Universität Erlangen-Nürnberg
end of 1:1-Block organizational data
start of 1:n-Block secondary IDs

Secondary IDs

  •   U1111-1112-2933 
  •   2009-009871-36 
  •   4035573 
end of 1:n-Block secondary IDs
start of 1:N-Block indications

Health Condition or Problem studied

  •   I50 -  Heart failure
end of 1:N-Block indications
start of 1:N-Block interventions

Interventions/Observational Groups

  •   run-in period with open up titration of beta-blocker and ACE inhibitor (Metoprolol-Succinat and Enalaprilmaleat) over 4x4 weeks with consideration of weight, oral application.

    Tablets with following dose:
    Metoprolol-Succinat: 23,75 g (mini), 47,5mg (medium) and 95 mg (forte); Enalaprilmaleat: 5 mg (medium) and 10 mg (forte).
    3 classes of weight: 20<45 kg , 45-60 kg, >60 kg;
    Starting dose: Metoprolol-Succinat : ½ Tablette mini, Enalaprilmaleat 1/ 2 Tablette medium for all classes of weight.
    Metoprolol-Succinat :1 Tablette medium, Enalaprilmaleat: 2x 1 Tablette medium for class 20<45 kg;
    Metoprolol-Succinat: 1 Tablette mini and 1 medium, Enalaprilmaleat:
    2x 1 Tablette medium for class 45-60 kg;
    Metoprolol-Succinat:1 Tablette forte, Enalaprilmaleat:2x 1 Tablette forte for class >60 kg ;

    experimental intervention: combined therapy with beta-blocker+ ACE-inhibitor versus placebo,double-blinded,
    duration of intervention per patient: max. 6 years
  •   Placebo
end of 1:N-Block interventions
start of 1:1-Block design


  •   Interventional
  •   [---]*
  •   Randomized controlled trial
  •   Blinded
  •   patient/subject, investigator/therapist
  •   Placebo
  •   Treatment
  •   Parallel
  •   II-III
  •   [---]*
end of 1:1-Block design
start of 1:1-Block primary endpoint

Primary Outcome

To evaluate the effect and safety of a preventive treatment with ACE-Inhibitor and a Beta-Blocker on the onset of Left Ventricular Dysfunction in Duchenne Muscular Dystrophy .
Time to first diagnosis of left ventricular dysfunction defined as fraction shortening < 28% in standard echocardiography.

end of 1:1-Block primary endpoint
start of 1:1-Block secondary endpoint

Secondary Outcome

Overall survival (time from randomization to death)
Quality of life (noted by Kindl-questionnaire) in both groups (baseline; once a year; end of study for individual patient or end of follow-up)
Mean drop of frequency and heart rate variability in 24h-ECG
Tissue-Doppler data: systolic and diastolic strain, strain rate and wall velocities in left and right ventricle
Laboratory parameters (pro-BNP, Angiotensin II, Noradrenalin)
assessment of safety: safety -laboratory (esp.Creatinine, Electrolytes,lowest blood pressure measurements, 24h ECG (heart rate, arrhythmias), Adverse Events

end of 1:1-Block secondary endpoint
start of 1:n-Block recruitment countries

Countries of Recruitment

  •   Germany
end of 1:n-Block recruitment countries
start of 1:n-Block recruitment locations

Locations of Recruitment

  • [---]*
end of 1:n-Block recruitment locations
start of 1:1-Block recruitment


  •   Actual
  •   2010/03/01
  •   55
  •   Multicenter trial
  •   National
end of 1:1-Block recruitment
start of 1:1-Block inclusion criteria

Inclusion Criteria

  •   Male
  •   10   Years
  •   14   Years
end of 1:1-Block inclusion criteria
start of 1:1-Block inclusion criteria add

Additional Inclusion Criteria

1. Male patients aged 10 - 14 years
2. Normal left ventricular function (LVSF >=30%)
3. DMD confirmed by genetic analysis (muscle biopsy facultative)
4. Normal renal function (GFR >30 ml/min/1,73 m2)
5. Informed Consent of both parents, assent of patient

end of 1:1-Block inclusion criteria add
start of 1:1-Block exclusion criteria

Exclusion Criteria

1. Contraindications for ACE-Inhibitors/Beta-Blocker.
2. Previous therapy with ACE-Inhibitors, AT II Antagonists, Beta-Blockers in the past 3 Months.
3. Participation in another one clinical Trial parallel to this clinical trial
4.Dilated left ventricle ( > 97 percentile) or reduced LVSF < 30%

end of 1:1-Block exclusion criteria
start of 1:n-Block addresses


  • start of 1:1-Block address primary-sponsor
    • Friedrich- Alexander- Universität Erlangen Nürnberg, Universitätsklinikum , Dekan
    • Mr.  Prof. Dr. med. Dr. h.c.  Jürgen  Schüttler 
    • Maximiliansplatz
    • 91054  Erlangen
    • Germany
    end of 1:1-Block address primary-sponsor
    start of 1:1-Block address contact primary-sponsor
    •   +49(0)913185-0
    •   +49(0)913185-39191
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact primary-sponsor
  • start of 1:1-Block address scientific-contact
    • Kinderkardiologische Abteilung in der Kinder und Jugendklinik
    • Mr.  Prof. Dr.  Sven  Dittrich 
    • Loschgestrasse 15
    • 91054  Erlangen
    • Germany
    end of 1:1-Block address scientific-contact
    start of 1:1-Block address contact scientific-contact
    end of 1:1-Block address contact scientific-contact
  • start of 1:1-Block address public-contact
    • Kinderkardiologische Abteilung in der Kinder und Jugendklinik Erlangen
    • Ms.  Verena  Greim 
    • Loschgestrasse 15
    • 91054  Erlangen
    • Germany
    end of 1:1-Block address public-contact
    start of 1:1-Block address contact public-contact
    end of 1:1-Block address contact public-contact
end of 1:n-Block addresses
start of 1:n-Block material support

Sources of Monetary or Material Support

  • start of 1:1-Block address materialSupport
    • Bundesministerium für Bildung und Forschung
    • Heinemannstr. 2
    • 53175  Bonn
    • Germany
    end of 1:1-Block address materialSupport
    start of 1:1-Block address contact materialSupport
    •   +49 (0)228/ 9957-0
    •   +49 (0)228/ 9957-83601
    •   [---]*
    end of 1:1-Block address contact materialSupport
end of 1:n-Block material support
start of 1:1-Block state


  •   Recruiting complete, follow-up complete
  •   2015/12/11
end of 1:1-Block state
start of 1:n-Block publications

Trial Publications, Results and other Documents

end of 1:n-Block publications
* This entry means the parameter is not applicable or has not been set.