A double-blind randomised multi-centre, placebo-controlled trial of combined angiotensin converting enzyme-inhibitor and beta-blocker therapy in preventing the development of cardiomyopathy in genetically characterised males with Duchenne Muscular Dystrophy without echo-detectable left ventricular dysfunction

ISRCTN	ISRCTN50395346
DOI	https://doi.org/10.1186/ISRCTN50395346
Clinical Trials Information System (CTIS)	2007-005932-10
Protocol serial number	1.1
Sponsor	Newcastle upon Tyne Hospitals NHS Foundation Trust (UK)
Funder	British Heart Foundation (UK)

Submission date: 12/06/2007
Registration date: 13/08/2007
Last edited: 31/12/2020

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nervous System Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr John Bourke
Scientific

Freeman Hospital
Newcastle upon Tyne
NE7 7DN
United Kingdom

Study information

Primary study design	Interventional
Study design	Double-blind randomised multi-centre placebo-controlled trial
Secondary study design	Randomised controlled trial
Scientific title	A double-blind randomised multi-centre, placebo-controlled trial of combined angiotensin converting enzyme-inhibitor and beta-blocker therapy in preventing the development of cardiomyopathy in genetically characterised males with Duchenne Muscular Dystrophy without echo-detectable left ventricular dysfunction
Study acronym	DMD Heart
Study objectives	To determine whether the introduction of Angiotensin Converting Enzyme-inhibitor (ACE-inhibitor) (perindopril) combined with beta-blocker therapy (bisoprolol), before the onset of echo-detectable left ventricular dysfunction, can delay the age of onset and/or slow the rate of progression of cardiomyopathy in males with Duchenne Muscular Dystrophy (DMD).
Ethics approval(s)	Ethics pending as of 12/06/2007. No patients will be recruited before ethics approval has been received.
Health condition(s) or problem(s) studied	Duchenne muscular dystrophy
Intervention	Presentation of Investigational Medicinal Product (IMP): Each participant will receive: 1. A one-month supply of perindopril 2 mg/bisoprolol 1.25 mg or placebo for the run-in period 2. Six-monthly supplies of perindopril 4 mg/bisoprolol 2.5 mg or placebo for the remainder of the trial Introduction of IMP or placebo therapies: The IMP or placebo therapy will be introduced in the following stepwise manner: Step 1: combined capsule containing perindopril 2 mg/bisoprolol 1.25 mg or matching placebo to be administered by parent(s)/legal guardian(s) at bedtime Step 2 (one month later): change to maintenance capsule containing perindopril 4 mg/bisoprolol 2.5 mg or matching placebo to be administered by parent(s)/legal guardian(s)at bedtime Treatment period is for two years. Follow up is for up to 60 months.
Intervention type	Drug
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Perindopril, bisoprolol
Primary outcome measure(s)	Change in left ventricular ejection fraction by Simpson's biplane disk method, compared to baseline, after a minimum of two years of combination therapy or placebo. To assess robustness of ejection fraction result, similar comparisons will be made for parameters of left ventricular end-systolic volume and wall motion index.
Key secondary outcome measure(s)	1. Death from any cause 2. Development of symptoms and signs of congestive cardiac failure 3. Sufficient objective deterioration in cardiac function, without symptoms to make continued placebo therapy unethical Secondary outcomes are measured at baseline and 6, 12, 18, 24, 30, 36, 42, 48, 54 and 60 months.
Completion date	30/03/2019

Eligibility

Participant type(s)	Patient
Age group	Child
Lower age limit	7 Years
Upper age limit	12 Years
Sex	Male
Target sample size at registration	140
Key inclusion criteria	1. Boys aged 7 to 12 years 2. Genetically confirmed DMD with normal left ventricular function on trans-thoracic echocardiography (i.e., left ventricular ejection fraction by Simpson's biplane method greater than 55% [normal mean + SD = 63 + 5%], no global or regional wall motion abnormalities)
Key exclusion criteria	1. Contraindication to ACE-inhibitor or beta-blocker therapy 2. Patients, whose initial echo is of insufficient quality to allow reliable measurements of ejection fraction or wall motion 3. Patients with abnormal echocardiograms at baseline 4. Patients with abnormal renal function (creatinine greater than upper limit of local laboratory range; typically greater than 120 mmol/l) or consistently abnormally high serum potassium level (K greater than upper limit of local laboratory range; typically 5 mmol/l)
Date of first enrolment	01/09/2007
Date of final enrolment	30/03/2018

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

Freeman Hospital

Newcastle upon Tyne
NE7 7DN
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Protocol article	protocol	19/12/2018	31/12/2020	Yes	No
Basic results				No	No

Editorial Notes

31/12/2020: The following changes have been made:
1. Publication reference added.
2. Added EudraCT/clinicaltrials.gov link to basic results (scientific).
17/01/2019: The following changes have been made to the trial record:
1. The overall trial end date has been changed from 01/09/2012 to 30/03/2019
2. The recruitment end date has been changed from 01/09/2012 to 30/03/2018
3. The intention to publish date has been added
04/10/2017: No publications found in PubMed, verifying study status with principal investigator