Preventing Cardiomyopathy in DMD: A Randomized Placebo-Controlled Drug Trial.

Autor:	Bourke JP; Department of Cardiology (JPB), Freeman Hospital, NUTH NHS Hospitals Foundation Trust; Clinical Trials Unit (MC, RW), Newcastle University, Newcastle upon Tyne; Department of Paediatric Neurology (SS), Alder Hey Children's NHS Foundation Trust, Liverpool; Population Health Sciences Institute (AB, TC, EM), Newcastle University, Newcastle upon Tyne; Department of Paediatrics (HR), Birmingham Heartlands Hospital, University Hospitals Birmingham NHS Foundation Trust; John Walton Muscular Dystrophy Research Centre (KB, MG), Newcastle University and Newcastle upon Tyne, NHS Hospitals Foundation Trust, Newcastle upon Tyne; and NIHR Great Ormond Street Hospital Biomedical Research Centre (FM), Great Ormond Street Institute of Child Health, University College London, & Great Ormond Street Hospital Trust, UK., Watson G; Department of Cardiology (JPB), Freeman Hospital, NUTH NHS Hospitals Foundation Trust; Clinical Trials Unit (MC, RW), Newcastle University, Newcastle upon Tyne; Department of Paediatric Neurology (SS), Alder Hey Children's NHS Foundation Trust, Liverpool; Population Health Sciences Institute (AB, TC, EM), Newcastle University, Newcastle upon Tyne; Department of Paediatrics (HR), Birmingham Heartlands Hospital, University Hospitals Birmingham NHS Foundation Trust; John Walton Muscular Dystrophy Research Centre (KB, MG), Newcastle University and Newcastle upon Tyne, NHS Hospitals Foundation Trust, Newcastle upon Tyne; and NIHR Great Ormond Street Hospital Biomedical Research Centre (FM), Great Ormond Street Institute of Child Health, University College London, & Great Ormond Street Hospital Trust, UK., Spinty S; Department of Cardiology (JPB), Freeman Hospital, NUTH NHS Hospitals Foundation Trust; Clinical Trials Unit (MC, RW), Newcastle University, Newcastle upon Tyne; Department of Paediatric Neurology (SS), Alder Hey Children's NHS Foundation Trust, Liverpool; Population Health Sciences Institute (AB, TC, EM), Newcastle University, Newcastle upon Tyne; Department of Paediatrics (HR), Birmingham Heartlands Hospital, University Hospitals Birmingham NHS Foundation Trust; John Walton Muscular Dystrophy Research Centre (KB, MG), Newcastle University and Newcastle upon Tyne, NHS Hospitals Foundation Trust, Newcastle upon Tyne; and NIHR Great Ormond Street Hospital Biomedical Research Centre (FM), Great Ormond Street Institute of Child Health, University College London, & Great Ormond Street Hospital Trust, UK., Bryant A; Department of Cardiology (JPB), Freeman Hospital, NUTH NHS Hospitals Foundation Trust; Clinical Trials Unit (MC, RW), Newcastle University, Newcastle upon Tyne; Department of Paediatric Neurology (SS), Alder Hey Children's NHS Foundation Trust, Liverpool; Population Health Sciences Institute (AB, TC, EM), Newcastle University, Newcastle upon Tyne; Department of Paediatrics (HR), Birmingham Heartlands Hospital, University Hospitals Birmingham NHS Foundation Trust; John Walton Muscular Dystrophy Research Centre (KB, MG), Newcastle University and Newcastle upon Tyne, NHS Hospitals Foundation Trust, Newcastle upon Tyne; and NIHR Great Ormond Street Hospital Biomedical Research Centre (FM), Great Ormond Street Institute of Child Health, University College London, & Great Ormond Street Hospital Trust, UK., Roper H; Department of Cardiology (JPB), Freeman Hospital, NUTH NHS Hospitals Foundation Trust; Clinical Trials Unit (MC, RW), Newcastle University, Newcastle upon Tyne; Department of Paediatric Neurology (SS), Alder Hey Children's NHS Foundation Trust, Liverpool; Population Health Sciences Institute (AB, TC, EM), Newcastle University, Newcastle upon Tyne; Department of Paediatrics (HR), Birmingham Heartlands Hospital, University Hospitals Birmingham NHS Foundation Trust; John Walton Muscular Dystrophy Research Centre (KB, MG), Newcastle University and Newcastle upon Tyne, NHS Hospitals Foundation Trust, Newcastle upon Tyne; and NIHR Great Ormond Street Hospital Biomedical Research Centre (FM), Great Ormond Street Institute of Child Health, University College London, & Great Ormond Street Hospital Trust, UK., Chadwick T; Department of Cardiology (JPB), Freeman Hospital, NUTH NHS Hospitals Foundation Trust; Clinical Trials Unit (MC, RW), Newcastle University, Newcastle upon Tyne; Department of Paediatric Neurology (SS), Alder Hey Children's NHS Foundation Trust, Liverpool; Population Health Sciences Institute (AB, TC, EM), Newcastle University, Newcastle upon Tyne; Department of Paediatrics (HR), Birmingham Heartlands Hospital, University Hospitals Birmingham NHS Foundation Trust; John Walton Muscular Dystrophy Research Centre (KB, MG), Newcastle University and Newcastle upon Tyne, NHS Hospitals Foundation Trust, Newcastle upon Tyne; and NIHR Great Ormond Street Hospital Biomedical Research Centre (FM), Great Ormond Street Institute of Child Health, University College London, & Great Ormond Street Hospital Trust, UK., Wood R; Department of Cardiology (JPB), Freeman Hospital, NUTH NHS Hospitals Foundation Trust; Clinical Trials Unit (MC, RW), Newcastle University, Newcastle upon Tyne; Department of Paediatric Neurology (SS), Alder Hey Children's NHS Foundation Trust, Liverpool; Population Health Sciences Institute (AB, TC, EM), Newcastle University, Newcastle upon Tyne; Department of Paediatrics (HR), Birmingham Heartlands Hospital, University Hospitals Birmingham NHS Foundation Trust; John Walton Muscular Dystrophy Research Centre (KB, MG), Newcastle University and Newcastle upon Tyne, NHS Hospitals Foundation Trust, Newcastle upon Tyne; and NIHR Great Ormond Street Hospital Biomedical Research Centre (FM), Great Ormond Street Institute of Child Health, University College London, & Great Ormond Street Hospital Trust, UK., McColl E; Department of Cardiology (JPB), Freeman Hospital, NUTH NHS Hospitals Foundation Trust; Clinical Trials Unit (MC, RW), Newcastle University, Newcastle upon Tyne; Department of Paediatric Neurology (SS), Alder Hey Children's NHS Foundation Trust, Liverpool; Population Health Sciences Institute (AB, TC, EM), Newcastle University, Newcastle upon Tyne; Department of Paediatrics (HR), Birmingham Heartlands Hospital, University Hospitals Birmingham NHS Foundation Trust; John Walton Muscular Dystrophy Research Centre (KB, MG), Newcastle University and Newcastle upon Tyne, NHS Hospitals Foundation Trust, Newcastle upon Tyne; and NIHR Great Ormond Street Hospital Biomedical Research Centre (FM), Great Ormond Street Institute of Child Health, University College London, & Great Ormond Street Hospital Trust, UK., Bushby K; Department of Cardiology (JPB), Freeman Hospital, NUTH NHS Hospitals Foundation Trust; Clinical Trials Unit (MC, RW), Newcastle University, Newcastle upon Tyne; Department of Paediatric Neurology (SS), Alder Hey Children's NHS Foundation Trust, Liverpool; Population Health Sciences Institute (AB, TC, EM), Newcastle University, Newcastle upon Tyne; Department of Paediatrics (HR), Birmingham Heartlands Hospital, University Hospitals Birmingham NHS Foundation Trust; John Walton Muscular Dystrophy Research Centre (KB, MG), Newcastle University and Newcastle upon Tyne, NHS Hospitals Foundation Trust, Newcastle upon Tyne; and NIHR Great Ormond Street Hospital Biomedical Research Centre (FM), Great Ormond Street Institute of Child Health, University College London, & Great Ormond Street Hospital Trust, UK., Muntoni F; Department of Cardiology (JPB), Freeman Hospital, NUTH NHS Hospitals Foundation Trust; Clinical Trials Unit (MC, RW), Newcastle University, Newcastle upon Tyne; Department of Paediatric Neurology (SS), Alder Hey Children's NHS Foundation Trust, Liverpool; Population Health Sciences Institute (AB, TC, EM), Newcastle University, Newcastle upon Tyne; Department of Paediatrics (HR), Birmingham Heartlands Hospital, University Hospitals Birmingham NHS Foundation Trust; John Walton Muscular Dystrophy Research Centre (KB, MG), Newcastle University and Newcastle upon Tyne, NHS Hospitals Foundation Trust, Newcastle upon Tyne; and NIHR Great Ormond Street Hospital Biomedical Research Centre (FM), Great Ormond Street Institute of Child Health, University College London, & Great Ormond Street Hospital Trust, UK., Guglieri M; Department of Cardiology (JPB), Freeman Hospital, NUTH NHS Hospitals Foundation Trust; Clinical Trials Unit (MC, RW), Newcastle University, Newcastle upon Tyne; Department of Paediatric Neurology (SS), Alder Hey Children's NHS Foundation Trust, Liverpool; Population Health Sciences Institute (AB, TC, EM), Newcastle University, Newcastle upon Tyne; Department of Paediatrics (HR), Birmingham Heartlands Hospital, University Hospitals Birmingham NHS Foundation Trust; John Walton Muscular Dystrophy Research Centre (KB, MG), Newcastle University and Newcastle upon Tyne, NHS Hospitals Foundation Trust, Newcastle upon Tyne; and NIHR Great Ormond Street Hospital Biomedical Research Centre (FM), Great Ormond Street Institute of Child Health, University College London, & Great Ormond Street Hospital Trust, UK.
Jazyk:	angličtina
Zdroj:	Neurology. Clinical practice [Neurol Clin Pract] 2021 Oct; Vol. 11 (5), pp. e661-e668.
DOI:	10.1212/CPJ.0000000000001023
Abstrakt:	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. (© 2021 American Academy of Neurology.)
Databáze:	MEDLINE
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