Center for Human Drug Research, Leiden, the Netherlands.
Department of Dermatology, Leiden University Medical Center, Leiden, the Netherlands.
Br J Dermatol. 2019 May;180(5):1058-1068. doi: 10.1111/bjd.17583. Epub 2019 Mar 7.
Topical ionic contraviral therapy (ICVT) with digoxin and furosemide inhibits the potassium influx on which DNA viruses rely for replication. Therefore, ICVT was hypothesized to be a potential novel treatment for cutaneous warts.
To assess the clinical efficacy, safety and tolerability of ICVT in adults with cutaneous warts. The secondary objective was to gain insight into the underlying working mechanism of ICVT.
Treatment with ICVT was assessed for efficacy, safety and tolerability in a single- centre, randomized, double-blind, placebo-controlled phase IIA trial. Eighty adult patients with at least two cutaneous warts (plantar or common) were randomized to one of four treatments: digoxin + furosemide (0·125%), digoxin (0·125%), furosemide (0·125%) or placebo. The gel was administered once daily for 42 consecutive days. Predefined statistical analysis was performed with a mixed-model ancova. The trial was registered at ClinicalTrials.gov with number NCT02333643.
Wart size and human papillomavirus (HPV) load reduction was achieved in all active treatment groups. A statistically significant reduction in wart diameter of all treated warts was shown in the digoxin + furosemide treatment group vs. placebo (-3·0 mm, 95% confidence interval -4·9 to -1·1, P = 0·002). There was a statistically significant reduction in the HPV load of all treated warts in the digoxin + furosemide group vs. placebo (-94%, 95% confidence interval -100 to -19, P = 0·03). With wart size reduction, histologically and immunohistochemically defined viral characteristics disappeared from partial and total responding warts.
This study demonstrates the proof of concept for the efficacy of topical ICVT in adults with cutaneous warts.
局部离子反病毒疗法（ICVT）联合地高辛和呋塞米可抑制 DNA 病毒复制所依赖的钾内流。因此，ICVT 被认为是一种治疗皮肤疣的潜在新型疗法。
评估 ICVT 治疗成人皮肤疣的临床疗效、安全性和耐受性。次要目的是深入了解 ICVT 的潜在作用机制。
在一项单中心、随机、双盲、安慰剂对照的 2A 期试验中，评估 ICVT 治疗的疗效、安全性和耐受性。80 例至少有 2 个皮肤疣（足底或常见）的成年患者随机分为 4 种治疗组之一：地高辛+呋塞米（0.125%）、地高辛（0.125%）、呋塞米（0.125%）或安慰剂。凝胶每天一次给药，连续 42 天。采用混合模型协方差进行了预先定义的统计分析。该试验在 ClinicalTrials.gov 上注册，编号为 NCT02333643。
所有活性治疗组均实现了疣大小和人乳头瘤病毒（HPV）载量的减少。与安慰剂相比，地高辛+呋塞米治疗组所有治疗疣的疣直径均显著缩小（-3.0mm，95%置信区间-4.9 至-1.1，P=0.002）。地高辛+呋塞米组所有治疗疣的 HPV 载量均显著减少（-94%，95%置信区间-100 至-19，P=0.03）。随着疣大小的缩小，部分和完全反应性疣的组织学和免疫组织化学定义的病毒特征消失。
本研究证明了局部 ICVT 在成人皮肤疣中的疗效概念验证。
