Preventing cardiomyopathy in DMD: a randomized placebo-controlled drug trial
Bourke, John P Watson, Gillian Spinty, Stefan Bryant, Andrew Roper, Helen Chadwick, Thomas Wood, Ruth McColl, Elaine Bushby, Kate Muntoni, Francesco
Bourke, John P
Watson, Gillian
Spinty, Stefan
Bryant, Andrew
Roper, Helen
Chadwick, Thomas
Wood, Ruth
McColl, Elaine
Bushby, Kate
Muntoni, Francesco
Abstract
Objective: To determine whether a combination of 2 heart medications would be tolerated and could prevent/delay the onset of cardiomyopathy in boys with Duchenne muscular dystrophy (DMD) compared with placebo.
Methods: This multicenter, parallel group, 1:1 patient randomized, placebo-controlled study of prophylactic perindopril and bisoprolol recruited boys with DMD aged 5-13 years, with normal ventricular function. Repeat assessments of left ventricular (LV) function, electrocardiogram, and adverse event reporting were performed 6 monthly. The primary outcome was change in ejection fraction between arms after 36 months. The study was approved by the National Research Ethics Service Committee East Midlands-Derby.
Results: Eighty-five boys were recruited (76% on steroid therapy) and randomized to combination heart drugs or matched placebo. Group change in left ventricular ejection fraction (LVEF%) at 36 months from baseline was -2.2% ± 6.0% and -2.9% ± 6.1% in active and placebo arms (adjusted mean difference: -2.1, 95% CI -5.2 to 1.1). There was no difference between treatment arms over repeated assessments (analysis of variance) up to 36 months (trial arms p = 0.53); arm-over-time (p = 0.44). Four participants on placebo but none on active therapy were withdrawn due to deteriorations in LV function. Secondary outcomes did not differ between arms either. Thirty-six serious adverse events occurred none due to cardiac events or trial medication.
Conclusions: Combination therapy was well tolerated. Consistent with the previous prophylactic perindopril heart study, there was no evidence of group benefit after 36-month treatment.
Classification of evidence: This study provides Class I evidence that combination perindopril-bisoprolol therapy was well tolerated but did not change decline in LVEF significantly in boys with DMD.
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Date
2020-12-03
Type
Article
Subject
Neurology, Diseases & disorders of the nervous system (e.g. Parkinson's), Paediatrics
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Citation
Bourke JP, Watson G, Spinty S, Bryant A, Roper H, Chadwick T, Wood R, McColl E, Bushby K, Muntoni F, Guglieri M; DMD Heart Study Group. Preventing Cardiomyopathy in DMD: A Randomized Placebo-Controlled Drug Trial. Neurol Clin Pract. 2021 Oct;11(5):e661-e668. doi: 10.1212/CPJ.0000000000001023.
Journal / Source Title
Neurology: Clinical Practice
DOI
10.1212/CPJ.0000000000001023
PMID
34840880
Publisher
Lippincott Williams & Wilkins
Publisher’s URL
https://www.neurology.org/journal/cpj