Hachulla Eric, Hatron Pierre-Yves, Carpentier Patrick, Agard Christian, Chatelus Emmanuel, Jego Patrick, Mouthon Luc, Queyrel Viviane, Fauchais Anne-Laure, Michon-Pasturel Ulrique, Jaussaud Roland, Mathian Alexis, Granel Brigitte, Diot Elisabeth, Farge-Bancel Dominique, Mekinian Arsène, Avouac Jérôme, Desmurs-Clavel Hélène, Clerson Pierre
Médecine Interne, Hopital Huriez, Université de Lille, Lille, France.
Médecine Vasculaire, CHU, Grenoble, France.
Ann Rheum Dis. 2016 Jun;75(6):1009-15. doi: 10.1136/annrheumdis-2014-207001. Epub 2015 May 20.
To assess the effect of sildenafil, a phosphodiesterase type 5 inhibitor, on digital ulcer (DU) healing in systemic sclerosis (SSc).
Randomised, placebo-controlled study in patients with SSc to assess the effect of sildenafil 20 mg or placebo, three times daily for 12 weeks, on ischaemic DU healing. The primary end point was the time to healing for each DU. Time to healing was compared between groups using Cox models for clustered data (two-sided tests, p=0.05).
Intention-to-treat analysis involved 83 patients with a total of 192 DUs (89 in the sildenafil group and 103 in the placebo group). The HR for DU healing was 1.33 (0.88 to 2.00) (p=0.18) and 1.27 (0.85 to 1.89) (p=0.25) when adjusted for the number of DUs at entry, in favour of sildenafil. In the per protocol population, the HRs were 1.49 (0.98 to 2.28) (p=0.06) and 1.43 (0.93 to 2.19) p=0.10. The mean number of DUs per patient was lower in the sildenafil group compared with the placebo group at week (W) 8 (1.23±1.61 vs 1.79±2.40 p=0.04) and W12 (0.86±1.62 vs 1.51±2.68, p=0.01) resulting from a greater healing rate (p=0.01 at W8 and p=0.03 at W12).
The primary end point was not reached in intention-to-treat, partly because of an unexpectedly high healing rate in the placebo group. We found a significant decrease in the number of DUs in favour of sildenafil compared with placebo at W8 and W12, confirming a sildenafil benefit.
NCT01295736.
评估5型磷酸二酯酶抑制剂西地那非对系统性硬化症（SSc）患者指端溃疡（DU）愈合的影响。
对SSc患者进行随机、安慰剂对照研究，以评估20mg西地那非或安慰剂每日三次、共12周对缺血性DU愈合的影响。主要终点是每个DU的愈合时间。使用Cox聚类数据模型在组间比较愈合时间（双侧检验，p = 0.05）。
意向性分析纳入83例患者，共192个DU（西地那非组89个，安慰剂组103个）。调整入组时DU数量后，DU愈合的风险比（HR）为1.33（0.88至2.00）（p = 0.18），支持西地那非；按方案分析人群中，HR为1.49（0.98至2.28）（p = 0.06）和1.43（0.93至2.19）（p = 0.10）。西地那非组患者每个患者的DU平均数在第8周（W8）（1.23±1.61 vs 1.79±2.40，p = 0.04）和第12周（W12）（0.86±1.62 vs 1.51±2.68，p = 0.01）低于安慰剂组，这是由于愈合率更高（W8时p = 0.01，W12时p = 0.03）。
意向性分析未达到主要终点，部分原因是安慰剂组愈合率意外地高。我们发现与安慰剂相比，西地那非在W8和W12时DU数量显著减少，证实了西地那非的益处。
NCT01295736。
