Eficácia do idebenone sobre a função respiratória em pacientes com distrofia muscular de Duchenne que não utilizam glicocorticóides (DELOS): estudo fase 3 - ensaio clínico controlado com placebo, randomizado, duplo-cego

USA - a insuficiência respiratória e cardíaca são as principais causas de óbito na distrofia muscular de Duchenne. Estudos prévios demonstraram que o debenone causa efeitos benéficos na distrofia muscular de Duchenne por melhorar as condições energéticas dos músculos. Neste estudo controlado fase 3 os pacientes foram tratados com idebenone (31 pacientes) (300mg, trës vezes ao dia) ou placebo (33 pacientes) por 52 semanas. A avaliação da função respiratória mostrou que a queda da função pulmonar foi menor nos tratados com idebenone, ficando a função pulmonar intermediária entre os tratados com corticóides e os que não tomaram nem corticóides e nem idebenone. Efeitos colaterais foram raros e a droga foi bem tolerada. O Idebenone reduziu a perda da função respiratória e representa uma nova opção de tratamento para pacientes com distrofia muscular de Duchenne.

O resumo em inglês pode ser lido abaixo:

(The Lancet, 2015) Efficacy of idebenone on respiratory function in patients with Duchenne muscular dystrophy not using glucocorticoids (DELOS): a double-blind randomised placebo-controlled phase 3 trial

Gunnar M Buyse, Thomas Voit, Ulrike Schara, Chiara S M Straathof, M Grazia D'Angelo, Günther Bernert, Jean-Marie Cuisset, Richard S Finkel, Nathalie Goemans, Craig M McDonald, Christian Rummey, Thomas Meier, for the DELOS Study Group


Cardiorespiratory failure is the leading cause of death in Duchenne muscular dystrophy. Based on preclinical and phase 2 evidence, we assessed the efficacy and safety of idebenone in young patients with Duchenne muscular dystrophy who were not taking concomitant glucocorticoids.


In a multicentre phase 3 trial in Belgium, Germany, the Netherlands, Switzerland, France, Sweden, Austria, Italy, Spain, and the USA, patients (age 10–18 years old) with Duchenne muscular dystrophy were randomly assigned in a one-to-one ratio with a central interactive web response system with a permuted block design with four patients per block to receive idebenone (300 mg three times a day) or matching placebo orally for 52 weeks. Study personnel and patients were masked to treatment assignment. The primary endpoint was change in peak expiratory flow (PEF) as percentage predicted (PEF%p) from baseline to week 52, measured with spirometry. Analysis was by intention to treat (ITT) and a modified ITT (mITT), which was prospectively defined to exclude patients with at least 20% difference in the yearly change in PEF%p, measured with hospital-based and weekly home-based spirometry. This study is registered with, number NCT01027884.


31 patients in the idebenone group and 33 in the placebo group comprised the ITT population, and 30 and 27 comprised the mITT population. Idebenone significantly attenuated the fall in PEF%p from baseline to week 52 in the mITT (−3·05%p [95% CI −7·08 to 0·97], p=0·134, vs placebo −9·01%p [–13·18 to −4·84], p=0·0001; difference 5·96%p [0·16 to 11·76], p=0·044) and ITT populations (−2·57%p [–6·68 to 1·54], p=0·215, vs −8·84%p [–12·73 to −4·95], p<0·0001; difference 6·27%p [0·61 to 11·93], p=0·031). Idebenone also had a significant effect on PEF (L/min), weekly home-based PEF, FVC, and FEV1. The effect of idebenone on respiratory function outcomes was similar between patients with previous corticosteroid use and steroid-naive patients. Treatment with idebenone was safe and well tolerated with adverse event rates were similar in both groups. Nasopharyngitis and headache were the most common adverse events (idebenone, eight [25%] and six [19%] of 32 patients; placebo, nine [26%] and seven [21%] of 34 patients). Transient and mild diarrhoea was more common in the idebenone group than in the placebo group (eight [25%] vs four [12%] patients).


Idebenone reduced the loss of respiratory function and represents a new treatment option for patients with Duchenne muscular dystrophy.