Instituto Conmemorativo Gorgas de Estudios de la Salud, Avenida Justo Arosemena, Panama City, Panama.
US Army Medical Materiel Development Activity (USAMMDA), Fort Detrick, MD, United States of America.
PLoS Negl Trop Dis. 2019 May 2;13(5):e0007253. doi: 10.1371/journal.pntd.0007253. eCollection 2019 May.
Paromomycin-based topical treatments were shown to be effective in curing cutaneous leishmaniasis (CL) lesions caused by Leishmania major in Tunisia. Cure rates of an index lesion were approximately 80%. As a follow on, we conducted a similar Phase 3 trial in Panama to demonstrate the efficacy of these treatments against New World species. The primary objective was to determine if a combination topical cream (paromomycin-gentamicin) resulted in statistically superior final clinical cure rates of an index lesion compared to a paromomycin alone topical cream for the treatment of CL, primarily caused by Leishmania panamensis.
We conducted a randomized, double blind, Phase 3 trial of topical creams for the treatment of CL caused by Leishmania spp. Three hundred ninety nine patients with one to ten CL lesions were treated by topical application once daily for 20 days. The primary efficacy endpoint was percentage of subjects with clinical cure of an index lesion confirmed to contain Leishmania with no relapse.
The clinical cure of the index lesion for paromomycin-gentamicin was 79% (95% CI; 72 to 84) and for paromomycin alone was 78% (95% CI; 74 to 87) (p = 0.84). The most common adverse events considered related to study cream application were mild to moderate dermatitis, pain, and pruritus.
Superiority of paromomycin-gentamicin was not demonstrated. However, the approximately 80% cure rates for both topical creams were similar to those demonstrated in Tunisia and previously reported with parenteral antimonials.
基于巴龙霉素的局部治疗已被证明可有效治愈突尼斯由利什曼原虫引起的皮肤利什曼病(CL)病变。一个病灶的治愈率约为 80%。在此基础上,我们在巴拿马进行了一项类似的 3 期试验,以证明这些治疗方法对新世界物种的疗效。主要目的是确定局部乳膏(巴龙霉素-庆大霉素)是否会导致主要由利什曼原虫引起的 CL 病变的最终临床治愈率相对于单独使用巴龙霉素的局部乳膏具有统计学上的优势。
我们进行了一项随机、双盲、3 期临床试验,评估了局部乳膏治疗利什曼原虫引起的 CL。399 例患有 1 至 10 个 CL 病变的患者每天接受一次局部治疗,共 20 天。主要疗效终点是包含利什曼原虫的病灶的临床治愈率,且无复发。
巴龙霉素-庆大霉素治疗组病灶的临床治愈率为 79%(95%置信区间;72 至 84),单独使用巴龙霉素的治愈率为 78%(95%置信区间;74 至 87)(p=0.84)。最常见的与研究乳膏应用相关的不良事件为轻度至中度皮炎、疼痛和瘙痒。
未证明巴龙霉素-庆大霉素具有优越性。然而,两种局部乳膏的治愈率均在 80%左右,与突尼斯的疗效和以前报告的注射用抗锑剂相似。