Drake L, Babel D, Stewart D M, Rich P, Ling M R, Breneman D, Scher R K, Martin A G, Pariser D M, Pariser R J, Ellis C N, Kang S, Katz H I, McDonald C J, Muglia J, Savin R C, Webster G, Elewski B E, Leyden J J, Bucko A D, Tschen E H, Hanifin J M, Morman M R, Shupack J L, Greer D L
Dermatology Clinical Investigations Unit, Massachusetts General Hospital, Boston 02114-2698, USA.
J Am Acad Dermatol. 1998 Jun;38(6 Pt 2):S87-94. doi: 10.1016/s0190-9622(98)70491-8.
Onychomycosis is a prevalent infection of the nail caused primarily by dermatophytes. Fluconazole is active in vitro against the most common pathogens, penetrates into the nail bed, and is clinically effective in the treatment of a wide variety of fungal infections.
The purpose of this study was to assess the safety and efficacy of oral fluconazole 150, 300, and 450 mg administered once weekly compared with placebo in the treatment of distal subungual onychomycosis of the fingernail caused by dermatophytes.
This was a multicenter, randomized, double-blind, placebo-controlled study enrolling 349 patients with onychomycosis of the fingernails. Clinical and mycologic efficacy as well as measures of safety were assessed monthly for a maximum of 9 months of treatment, with additional safety visits occurring at weeks 2 and 6. For inclusion, patients were required to have clinically and mycologically documented onychomycosis of the fingernail caused by dermatophytes with at least 25% involvement of the target fingernail. After end of therapy, patients with improved or cured fingernails entered a blinded 6-month follow-up without drug treatment during which efficacy was assessed every 2 months. Efficacy was assessed by clinical (visual) and mycologic (microscopic and culture) measures. Clinical measures included assessments of the percentage of target nail involvement, measurement of the distance from the nail fold to the proximal onychomycotic border, and signs and symptoms of onychomycosis.
Fluconazole was significantly superior to placebo in eradicating clinical and mycologic symptoms of onychomycosis, both at the end of active treatment and at 6 months after treatment (p=0.0001 for all efficacy measures). At the end of therapy, 91% to 100% of patients in the fluconazole groups were judged clinical successes, defined as reduction of the affected area of the target nail to less than 25% or cure, compared with 8% for placebo. Clinical cure rates at end of therapy were 76%, 85%, and 90% for fluconazole 150, 300, and 450 mg, respectively, compared with 3% for placebo. These clinical success and cure rates were largely maintained or improved during follow-up. Clinical relapse in cured patients during the follow-up period was very low (1.5% to 3.3%). Fluconazole demonstrated mycologic eradication rates of 89% to 100% at the end of treatment and 90% to 99% at the end of follow-up; for placebo the rates were 8% and 12%, respectively.
Fluconazole administered once weekly is safe and effective in eradicating distal subungual onychomycosis of the fingernail caused by dermatophytes.
甲癣是一种主要由皮肤癣菌引起的常见指甲感染。氟康唑在体外对最常见的病原体具有活性，可渗透至甲床，并且在治疗多种真菌感染方面临床有效。
本研究的目的是评估每周一次口服150、300和450mg氟康唑与安慰剂相比，在治疗由皮肤癣菌引起的手指甲远端甲下型甲癣中的安全性和有效性。
这是一项多中心、随机、双盲、安慰剂对照研究，纳入了349例手指甲癣患者。在最长9个月的治疗期间每月评估临床和真菌学疗效以及安全性指标，在第2周和第6周进行额外的安全性访视。纳入标准为患者需有临床和真菌学证实的由皮肤癣菌引起的手指甲癣，目标指甲受累至少25%。治疗结束后，指甲改善或治愈的患者进入为期6个月的盲法随访，随访期间不进行药物治疗，每2个月评估一次疗效。疗效通过临床（视觉）和真菌学（显微镜检查和培养）指标进行评估。临床指标包括目标指甲受累百分比的评估、从甲皱襞到近端甲癣边界的距离测量以及甲癣的体征和症状。
在积极治疗结束时和治疗后6个月，氟康唑在根除甲癣的临床和真菌学症状方面均显著优于安慰剂（所有疗效指标p=0.0001）。治疗结束时，氟康唑组91%至100%的患者被判定为临床成功，定义为目标指甲受累面积减少至小于25%或治愈，而安慰剂组为8%。治疗结束时，氟康唑150mg、300mg和450mg组的临床治愈率分别为76%、85%和90%，而安慰剂组为3%。这些临床成功率和治愈率在随访期间基本保持或有所提高。随访期间治愈患者的临床复发率非常低（1.5%至3.3%）。氟康唑在治疗结束时的真菌清除率为89%至100%，随访结束时为90%至99%；安慰剂组的真菌清除率分别为8%和12%。
每周一次服用氟康唑在根除由皮肤癣菌引起的手指甲远端甲下型甲癣方面安全有效。
