Long-term follow-up of heart function in participants of the Duchenne Muscular Dystrophy Heart Protection study
| ISRCTN | ISRCTN43827539 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN43827539 |
| IRAS number | 269110 |
| Secondary identifying numbers | IRAS 269110, 09825, CPMS 49264 |
- Submission date
- 17/04/2023
- Registration date
- 11/09/2023
- Last edited
- 19/12/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nervous System Diseases
Plain English summary of protocol
Background and study aims
Almost all boys with Duchenne muscular dystrophy (DMD) develop progressive cardiomyopathy. The DMD Heart-Protection Study (https://www.isrctn.com/ISRCTN50395346) tested whether starting perindopril and bisoprolol in combination before evidence of dysfunction of the heart muscle (ventricular dysfunction) could delay the onset of cardiomyopathy. The study ended in 2018 after 75 boys had been studied for three years. Although left ventricular dysfunction did occur in some participants, there was not a group benefit for active therapy in the primary endpoint. This may be explained by the fact that most participants were also getting the benefits of maintenance steroids combined with inter-patient variability in the age of cardiomyopathy onset meaning that longer follow-up data are needed to show outcome differences. This study aims to reanalyse data between the groups from baseline after adding 2-3 years of further data obtained from normal NHS review to the original dataset. No additional testing or hospital visits are required. International experts and patient group advocates agree on the importance of longer follow-up of this patient cohort to determine the role of prophylactic heart therapy in young boys with DMD.
Who can participate?
Males with DMD who participated in the original DMD Heart Protection study
What does the study involve?
This 'follow-on' study aims to collect and analyse heart measurements from evaluations done on the original participants for longer (eg: extend the minimum follow-up to 5 years) and re-analyse according to what treatment participants were randomized to originally. Males with DMD typically have heart assessments annually. This study does not require any additional testing or hospital visits for patients/families but does require re-consenting to allow the data accumulated since each participant exited the study to be transferred securely from clinical teams caring for these patients to researchers. Participants were all recommended active heart treatments as they exited the DMD Heart Protection Study. So, those originally taking 'dummy' drugs during the study have also been on unblinded active therapy since then.
Because best practice recommendations, developed by consensus since this study ended, now recommend prophylactic heart therapy empirically from age 10 years, it will not be possible to conduct a further placebo-controlled study of this kind. Therefore, extending follow-up in the DMD Heart-Protection cohort provides a unique opportunity to determine whether it is better to start a combination of heart drugs at a younger age in boys with DMD, while heart function is still healthy than starting the same drugs 3-5 years later with the onset of ventricular dysfunction. Collating and reanalysing these additional measures are central to establishing the evidence-base underpinning recently updated international recommendations on the use of conventional heart drugs prophylactically in boys with DMD.
What are the possible benefits and risks of participating?
No benefits will accrue to individual participants. The findings should clarify the indeterminate results at the end of the three-year follow-up from the original study. Crucially, the longer-term findings are expected to establish the clinical utility of introducing two heart medications prophylactically in combination in young males with DMD to slow the development of cardiomyopathy. No risks are anticipated for participants or carers, and none have been identified.
Where is the study run from?
Newcastle upon Tyne NHS Hospitals Foundation Trust (UK)
When is the study starting and how long is it expected to run for?
December 2020 to July 2023
Who is funding the study?
Duchenne UK (UK)
Who is the main contact?
Dr JP Bourke, john.bourke@nhs.net (UK)
Contact information
Principal Investigator
Chief Investigator for the study
Consultant Cardiologist
Department of Cardiology
Freeman Hospital
NUTH NHS Hospitals Foundation Trust
Newcastle upon Tyne
NE7 7DN
United Kingdom
 ORCID ID |
0000-0001-7857-9073 |
|---|---|
| Phone | +44 (0)191 223 1546 |
| john.bourke@nhs.net |
Public
Trial Manager
Research Project Manager
Newcastle Joint Research Office
Newcastle University/The Newcastle upon Tyne Hospitals NHS Foundation Trust
Level 1, Regent Point
Regent Farm Road
Gosforth
Newcastle upon Tyne
NE3 3HD
United Kingdom
| Phone | +44 (0)191 282 4823 |
|---|---|
| nuth.projectmanagement@nhs.net |
Scientific
Study Statistician
Institute of Health and Society
Baddiley Clark Building
Richardson Road
Newcastle University
Newcastle upon Tyne
NE2 4AX
United Kingdom
| Phone | +44 (0)191 208 6039 |
|---|---|
| thomas.chadwick@newcastle.ac.uk |
Scientific
Study Statistician
Institute of Health and Society
Baddiley Clark Building
Richardson Road
Newcastle University
Newcastle upon Tyne
NE2 4AX
United Kingdom
| Phone | None available |
|---|---|
| andy.bryant@newcastle.ac.uk |
Study information
| Study design | Observational study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Long term follow-up of measures of heart function in participants in a double-blind, randomised, placebo-controlled trial. |
| Study setting(s) | Medical and other records, University/medical school/dental school |
| Study type | Diagnostic |
| Participant information sheet | Not available in web-format |
| Scientific title | Long-term follow-up of heart function in participants of the Duchenne Muscular Dystrophy Heart Protection study |
| Study acronym | DMD Heart Protection study follow-up |
| Study objectives | The null hypothesis is that prophylactic therapy with an ACE-inhibitor (perindopril) and beta-blocker (bisoprolol) in combination will neither delay the onset nor slow the rate of progression of left ventricular systolic dysfunction compared to placebo over five to six years of follow-up. |
| Ethics approval(s) | Approved 24/06/2021, London - Brent Research Ethics Committee (80 London Road, Skipton House, London, SE1 6LH, UK; +44 (0)20 7104 8128, (0)20 7104 8137; brent.rec@hra.nhs.uk), ref: 21/PR/0595 |
| Health condition(s) or problem(s) studied | Duchenne muscular dystrophy-related cardiomyopathy |
| Intervention | Almost all boys with Duchenne muscular dystrophy (DMD) develop progressive cardiomyopathy. The prior multicentre, randomized, placebo-controlled, Heart-Protection Study ['A double-blind randomized, multi-center, placebo-controlled trial of combined ACE-inhibitor and beta-blocker therapy in preventing cardiomyopathy in genetically characterized males with DMD without echo-detectable left ventricular dysfunction'] (LV) tested whether starting perindopril and bisoprolol in combination before evidence of LV dysfunction could delay the onset of cardiomyopathy. The study ended in 2018 after 75 boys had been studied for three years. Although LV dysfunction did occur in some participants, there was not a group benefit for active therapy in the primary endpoint (ie: change in LVEF% from baseline). This may be explained by the fact that most participants were also getting the benefits of maintenance steroids and this, combined with inter-patient variability in the age of cardiomyopathy onset, meaning that longer follow-up was needed to show outcome differences. This proposal aims to reanalyse the change in LVEF% between groups from baseline after adding 2-3 years of data, obtained from normal NHS review, to the original dataset. No additional testing or hospital visits are required. International experts and patient group advocates agree on the importance of longer follow-up of this patient cohort to determine the role of prophylactic heart therapy in young boys with DMD. Measures of exposure International Standards of Care recommend that patients with DMD undergo cardiac testing at least annually as part of routine NHS care. This extension / ‘follow-on’ phase simply aims to collect and analyse heart test results from heart scans done on the original participants since their participation in the DMD Heart Protection study ended, add the extra serial measures to the original data set and re-compare the groups according to their initial treatment randomization (‘active’ vs ‘placebo’). The proposal does not require any additional testing or hospital visits for patients/families. Primary outcome measure / Follow-up duration Change in LV ejection fraction from original study enrolment ('baseline') after a minimum follow-up of five years from initial recruitment (2011-2015). The study team expects to have a 6-year follow-up with most participants. Proposed sample size/power calculation / lost to follow-up The sample size is dictated by the original number of participants [n=85], the number who continued to study end [n=75] and those who will provide consent. Some will have transitioned from paediatric to adult cardiology care and results will be obtained from wherever heart tests were undertaken. |
| Intervention type | Other |
| Primary outcome measure | Change in echocardiogram-measured left ventricular ejection fraction measured using electronic medical records from initial recruitment to study end |
| Secondary outcome measures | 1. Change in left ventricular fractional shortening and left ventricular chamber dimensions measured using electronic medical records from initial recruitment to study end 2. Sub-group analysis may be measured using electronic medical records from initial recruitment to study end. Pre-specified sub-group analyses may include: 2.1. Steroid use versus steroid naive patients 2.2. Actual therapy received since original study exit 2.3. Participant age at onset of detectable cardiomyopathy 2.4 Use of other DMD-modifying therapies (ie: exon skipping; ataluren; adenovirus gene therapy or similar). |
| Overall study start date | 18/12/2020 |
| Completion date | 30/07/2023 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | All |
| Sex | Male |
| Target number of participants | 75-85 |
| Key inclusion criteria | 1. Participated in the original DMD Heart Protection study (https://www.isrctn.com/ISRCTN50395346) 2. Valid consent of boys/parent or carer (age dependent) to allow access to serial measures of heart function and limited other data wherever undertaken, from the time each participant exited the original study |
| Key exclusion criteria | 1. Did not participate in the original DMD Heart Protection study 2. Refusal of re-consent |
| Date of first enrolment | 10/01/2022 |
| Date of final enrolment | 30/06/2023 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
High Heaton
Newcastle upon Tyne
NE7 7DN
United Kingdom
London
WC1N 3JH
United Kingdom
28-30 Fowler Road
Hainault
Ilford
IG6 3UT
United Kingdom
Heartlands Hospital
Birmingham
B9 5SS
United Kingdom
Sponsor information
Charity
Unit G20, Shepherd’s Building
Charecroft Way
Hammersmith
London
W14 0EE
England
United Kingdom
| Phone | +44 (0)203 198 6381 |
|---|---|
| duchenne@duchenneuk.org | |
| Website | http://www.duchenneuk.org/ |
Funders
Funder type
Charity
Government organisation / Other non-profit organizations
- Alternative name(s)
- Duchenne UK, THE DUCHENNE RESEARCH FUND, DRF
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 30/05/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Planned publication in a high-impact and peer-reviewed journal. Results are expected to be available in late 2023. |
| IPD sharing plan | The data-sharing plans for the current study are unknown and will be made available later |
Editorial Notes
19/12/2024: The intention to publish date was changed from 30/06/2024 to 30/05/2025.
04/10/2023: Internal review.
21/04/2023: Trial's existence confirmed by Health Research Authority (HRA) (UK).
