Comparison of Five Treatments in Patients With Plantar Warts (VRAIE)

Comparison of Occlusive Dressings, Salicylate Ointment, Cryotherapy, Topical 5-fluoro-uracil and Imiquimod in Immunocompetent Patients Presenting Plantar Warts in Office-based Settings: a Randomized Clinical Trial

The principal objective of the study is to compare 5 usual strategies in the management of plantar warts which did not cure after 5 weeks of a salicylate ointment given just prior the trial. The trial will include immunocompetent patients coming from the community and should help the office-based dermatologists and hospital in the decision-making therapeutic process.

Study Overview

• Status: Terminated
• Conditions: Plantar Warts
• Intervention / Treatment: Drug: Salicylate ointment; Drug: Imiquimod; Drug: 5-Fluoro-Uracil; Drug: Cryotherapy

Detailed Description

Four and a half million individuals in France have warts (SOFRES poll 2002). Notably, plantar warts are considered to be the most common reason for consulting a private practitioner, despite the absence of robust epidemiological data. Although benign, plantar warts are associated with a certain degree of morbidity: pain, difficulty walking, and intra- and interindividual contagion. Despite the frequency of plantar warts and patients high expectations for their treatments, which are numerous for immunocompetent patients, those remedies have only been evaluated in undeniably inadequate ways. Patient demand for therapy is strong, with those affected going from one physician to another, in the search for the "good treatment". For all the reasons evoked in the context of skin diseases, healing warts can indeed represent a public health objective.

One of the difficulties of evaluating treatments is the frequency of spontaneous complete remissions (natural history) and/or under placebo, assessed at 30% [range: 0-73%] in a short-term trial (10 weeks). In addition, professionals experiences support frequent relapses that have been very poorly evaluated in therapeutic trials.

Keratolytic treatment, usually salicylated petroleum jelly, is the standard therapy according to the Cochrane Review. In practice, this therapy usually combines manual shaving, done by the patient him/herself or the physician. Supplementing this basic therapy with a physical (standard cryotherapy), chemical (5-fluorouracil; Efudix®) or immunological adjunct (imiquimod; Aldara®), to achieve the desired effect of increasing the frequency and/or rapidity of complete cure, has never been examined in a large randomized-controlled trial.

A population comprised of patients with warts still "resistant" after 5 weeks of keratolytic therapy with 50% salicylic acid (PommadeM.O Cochon®) followed by a 1-week washout was deliberately retained because it is this precise setting that poses therapeutic difficulties in routine practice. The 1-week washout will allow the skin to heal a little and facilitate the diagnosis of failures; and, moreover, the strategy of pretreatment with scraping would not be unduly weakened.

• Study Type: Interventional
• Enrollment (Actual): 358
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Athis Mons, France, 91200
    • Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female patient aged 18 years or more.
• Clinical evaluation
• Number of warts lower than 10 on the 2 feet and total diameter of warts lower than 10 cm, whether previously treated or not
• In treated patients, all potentially active treatment on warts since at least one month should be stopped.
• Effective contraception for women of childbearing age
• Immunocompetent patients

• Patient with one or more warts on soles and board feet.

  • MYRMECIE : rounded warts, deep, covered with a stratum corneum more or less thick; after stripping, appear black points, very specific; often painful to pressure. They are lonely, single or not. They could regroup galley thick. The stripping can them to individualize.
  • Mosaic : plate small warts, superficial, often sitting on the heel or Forefoot. Little painful, they are often ignored by the patients when they appear
• Patient affiliated to the French social security.

Exclusion Criteria:

• Patient suspected to be immunocompromised
• Patient aged under 18 years
• Patient refusing to sign the consent
• Pregnant or lactating women
• Plantar calluses
• Known hypersensitivity to imiquimod (Aldara®) or any excipients of the cream (isostearic acid, benzyl alcohol, cetyl alcohol, stearyl alcohol, paraffin, polysorbate 60, sorbitan stearate, glycerol, methyl hydroxybenzoate, propyl hydroxybenzoate, xanthan gum, purified water)
• Known hypersensitivity to 5 fluoro-uracil (Efudix®) or any excipients of gel (stearyl alcohol, Vaseline, polysorbate 60, propyleneglycol, purified water - conservatives: METHYL PARAHYDROXYBENZOATE, PROPYL PARAHYDROXYBENZOATE)
• Contra-indication to Pomade M.O Cochon® (Known allergy to any components)
• Known hypersensitivity to Blenderm®
• Extra plantar concomitant warts (to exclude risk of endogenous recontamination by an extra plantar site)
• Plantar hyperhidrosis making impossible adhesion of plaster.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Salicylate ointment; Salicylate ointment under occlusion (pomade M.O Cochon®)	Drug: Salicylate ointment; cream, one application every night, for 90 days; Other Names: pommade M.O Cochon®
Experimental: Imiquimod; Imiquimod : Aldara®	Drug: Imiquimod; cream, one dose of 250 mg, one application 3 times a week during 12 hours, for 90 days; Other Names: Aldara® 5%
Experimental: 5-fluoro-uracil; 5-fluoro-uracil cream : Efudix®	Drug: 5-Fluoro-Uracil; cream, one application every night, during 12 hours, for 90 days; Other Names: Efudix® 5%
Experimental: Cryotherapy; liquid nitrogen : Cryotherapy	Drug: Cryotherapy; 2 cycles of 5 seconds after obtention of halo of white; Other Names: Liquid nitrogen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Complete clinical remission of the warts assessed by the dermatologist	at 90 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Time remission	at 30, 60 and 90 days
Number of warts in remission vs baseline	at 30, 60 and 90 days
Time to first relapse	at 30, 60, 90, 120, 180, 360 and 720 days
Percentage of relapse (phone call assessment)	at 360 days and 720 days
Safety	at 90 days
Evaluation of distress (visual analogic scale)	at 90 days
Compliance.	at 90 days

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Society of Dermatology and venerology
• Investigators: Principal Investigator: Olivier CHOSIDOW, MD,PhD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (Actual): January 1, 2015
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: November 30, 2009
• First Submitted That Met QC Criteria: January 28, 2010
• First Posted (Estimate): January 29, 2010

Study Record Updates

• Last Update Posted (Estimate): January 11, 2017
• Last Update Submitted That Met QC Criteria: January 10, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: Randomized clinical trial; Cryotherapy; Imiquimod; Occlusive dressings; Salicylate ointment; Topical 5-fluoro-uracil; Plantar warts
• Additional Relevant MeSH Terms: Skin Diseases; Virus Diseases; Infections; Musculoskeletal Diseases; DNA Virus Infections; Skin Diseases, Infectious; Papillomavirus Infections; Skin Diseases, Viral; Tumor Virus Infections; Warts; Foot Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Adjuvants, Immunologic; Interferon Inducers; Fluorouracil; Imiquimod; Salicylates
• Other Study ID Numbers: P070701