A randomized controlled proof-of-concept trial of digoxin and furosemide in adults with cutaneous warts

Br J Dermatol. 2019 May;180(5):1058-1068. doi: 10.1111/bjd.17583. Epub 2019 Mar 7.


Background: 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.

Objectives: 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.

Methods: 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.

Results: 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.

Conclusions: This study demonstrates the proof of concept for the efficacy of topical ICVT in adults with cutaneous warts.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Administration, Cutaneous
  • Adolescent
  • Adult
  • Digoxin / administration & dosage*
  • Digoxin / adverse effects
  • Double-Blind Method
  • Drug Therapy, Combination / adverse effects
  • Drug Therapy, Combination / methods
  • Female
  • Furosemide / administration & dosage*
  • Furosemide / adverse effects
  • Humans
  • Male
  • Papillomaviridae / drug effects*
  • Papillomaviridae / isolation & purification
  • Proof of Concept Study
  • Treatment Outcome
  • Viral Load / drug effects
  • Warts / drug therapy*
  • Warts / virology
  • Young Adult


  • Digoxin
  • Furosemide

Associated data

  • ClinicalTrials.gov/NCT02333643