Victor Ronald G, Sweeney H Lee, Finkel Richard, McDonald Craig M, Byrne Barry, Eagle Michelle, Goemans Nathalie, Vandenborne Krista, Dubrovsky Alberto L, Topaloglu Haluk, Miceli M Carrie, Furlong Pat, Landry John, Elashoff Robert, Cox David
From the Cedars-Sinai Medical Center (R.G.V.), Los Angeles, CA; University of Florida (H.L.S., B.B., K.V.), Gainesville; Nemours Children's Hospital (R.F.), Orlando, FL; University of California at Davis (C.M.M.), Sacramento; Newcastle University (M.E.), Newcastle Upon Tyne, UK; University Hospitals Leuven (N.G.), Belgium; Instituto de Neurociencias-Fundacion Favaloro (A.L.D.), Buenos Aires, Argentina; Hacettepe University School of Medicine (H.T.), Ankara, Turkey; UCLA (M.C.M., R.E.), Los Angeles, CA; Parent Project Muscular Dystrophy (P.F.), Hackensack, NJ; Eli Lilly Canada, Eli Lilly and Company, Toronto, ON (J.L.); and Eli Lilly and Company (D.C.), Indianapolis, IN.
Neurology. 2017 Oct 24;89(17):1811-1820. doi: 10.1212/WNL.0000000000004570. Epub 2017 Sep 29.
To conduct a randomized trial to test the primary hypothesis that once-daily tadalafil, administered orally for 48 weeks, lessens the decline in ambulatory ability in boys with Duchenne muscular dystrophy (DMD).
Three hundred thirty-one participants with DMD 7 to 14 years of age taking glucocorticoids were randomized to tadalafil 0.3 mg·kg·d, tadalafil 0.6 mg·kg·d, or placebo. The primary efficacy measure was 6-minute walk distance (6MWD) after 48 weeks. Secondary efficacy measures included North Star Ambulatory Assessment and timed function tests. Performance of Upper Limb (PUL) was a prespecified exploratory outcome.
Tadalafil had no effect on the primary outcome: 48-week declines in 6MWD were 51.0 ± 9.3 m with placebo, 64.7 ± 9.8 m with low-dose tadalafil ( = 0.307 vs placebo), and 59.1 ± 9.4 m with high-dose tadalafil ( = 0.538 vs placebo). Tadalafil also had no effect on secondary outcomes. In boys >10 years of age, total PUL score and shoulder subscore declined less with low-dose tadalafil than placebo. Adverse events were consistent with the known safety profile of tadalafil and the DMD disease state.
Tadalafil did not lessen the decline in ambulatory ability in boys with DMD. Further studies should be considered to confirm the hypothesis-generating upper limb data and to determine whether ambulatory decline can be slowed by initiation of tadalafil before 7 years of age.
NCT01865084.
This study provides Class I evidence that tadalafil does not slow ambulatory decline in 7- to 14-year-old boys with Duchenne muscular dystrophy.
进行一项随机试验，以检验主要假设，即每日口服他达拉非48周可减轻杜氏肌营养不良症（DMD）男孩的行走能力下降。
331名7至14岁正在服用糖皮质激素的DMD参与者被随机分为他达拉非0.3毫克·千克·天组、他达拉非0.6毫克·千克·天组或安慰剂组。主要疗效指标为48周后的6分钟步行距离（6MWD）。次要疗效指标包括北极星行走评估和定时功能测试。上肢功能表现（PUL）是预先设定的探索性结果。
他达拉非对主要结局无影响：安慰剂组48周内6MWD下降51.0±9.3米，低剂量他达拉非组（=0.307，与安慰剂相比）为64.7±9.8米，高剂量他达拉非组（=0.538，与安慰剂相比）为59.1±9.4米。他达拉非对次要结局也无影响。在10岁以上男孩中，低剂量他达拉非组的总PUL评分和肩部子评分下降幅度小于安慰剂组。不良事件与他达拉非已知的安全性特征及DMD疾病状态相符。
他达拉非未能减轻DMD男孩的行走能力下降。应考虑进一步研究以证实产生假设的上肢数据，并确定在7岁之前开始使用他达拉非是否能减缓行走能力下降。
NCT01865084。
本研究提供I类证据表明，他达拉非不能减缓7至14岁杜氏肌营养不良症男孩的行走能力下降。
