Condition category
Infections and Infestations
Date applied
19/03/2020
Date assigned
03/04/2020
Last edited
03/08/2020
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting
Publication status
Results

Plain English Summary

Background and study aims
Genital warts is a common sexually transmitted infection (STI) passed on through vaginal, anal and, rarely, oral sex.
In this study the researchers want to evaluate the effectiveness of Verrutop®, a solution based on Nitrizinc Complex, a recently marketed medical device for the painless treatment of external genital warts, by means of a comparative procedure with Cryotherapy, one of the most common methods in clinical practice with 55% efficacy data. Verrutop® performs a selective action on the wart, sparing healthy skin; this determines a low invasiveness of the treatment with a lower incidence of side effects and post-treatment outcomes; in addition, nitric oxide, which is generated during therapy with Verrutop®, performs an antiviral action thus reducing the risk of recurrence.

Who can participate?
Adults over 18 years, with more than three untreated ano genital warts.

What does the study involve?
Participants will be randomly allocated to receive treatment for warts using either cryotherapy or Verrutop®: solution based on Nitrizinc Complex®. Each patient will receive up to four applications of the treatment as deemed necessary by the doctor. Treatment will last up to one month and there will be a follow-up appointment at three months.

What are the possible benefits and risks of participating?
Benefits:
Effectiveness of both treatments in the partial and/or complete elimination of external genital warts; from the literature data Verrutop® should be more effective than Cryotherapy (75% vs 55%), the advantages in the use of Verrutop® are the non-invasiveness of the treatment as it is able to act directly on the lesion excluding the periwound skin and less risk of recurrence thanks to the antiviral action mediated by nitric oxide released during application.
Risks:
Side effects are extremely rare and, in any case, occur only locally.
Cryotherapy is often accompanied by the appearance of burning pain at the application site; in the following days a bullous lesion is formed which evolves into erosion. Complete re-epithelialization is generally accomplished in 7-10 days. This result can leave hypopigmentary and / or cicatricial results, especially if carried out on dark phototypes. Rarely, hypertrophic scars or small horny cysts can form.
Verrutop® is a substantially painless and selective treatment on the pathological tissue; therefore the therapeutic action focuses only on the wart with the saving of healthy tissue. Thanks to its mechanism of action which causes the "mummification" of the wart, Verrutop® does not cause ulceration and, consequently, does not cause scarring or hypopigmentary outcomes.

Where is the study run from?
1. Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (Italy)
2. Ospedale San Lazzaro (Italy)
3. Policlinico Sant'Orsola-Malpighi (Italy)

When is the study starting and how long is it expected to run for?
December 2017 to August 2019

Who is funding the study?
ISDIN (Spain)

Who is the main contact?
Dr Marco Cusini
marco.cusini@policlinico.mi.it

Trial website

Contact information

Type

Scientific

Primary contact

Dr Marco Cusini

ORCID ID

http://orcid.org/0000-0003-4757-6798

Contact details

Dermatology Unit
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Via Pace
9
Milan
20122
Italy
+39 (0)2 5503 5236
marco.cusini@policlinico.mi.it

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

1850/2017

Study information

Scientific title

Comparative efficacy study between "Nitrizinc complex®" and cryotherapy in the treatment of external genital warts

Acronym

Study hypothesis

Nitrizinc complex® is more effective than cryotherapy in the treatment of genital warts

Ethics approval

Approved 23/11/2017, IRCCS Ospedale Maggiore Policlinico - Ca Granda Foundation (Segreteria Comitato Etico, Ospedale Maggiore Policlinico, Milano, Area 2, Italy; +39 (0)2 5503 5832; isabella.damilano@policlinico.mi.it), ref: 1850

Study design

Multicenter prospective randomized comparative study

Primary study design

Interventional

Secondary study design

Randomised parallel trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Ano genital warts

Intervention

Patients are assigned to one of the two arms according to a specially prepared block randomization list of 4 patients. Only after the enrollment of each patient does the statistician communicate to the clinicians the treatment to be assigned in order to better guarantee the randomization management.

Cryotherapy: treatment based on the application of liquid nitrogen; Nitrogen is an inert, non-flammable gas which, in the liquid state found -196 ° C, is a suitable temperature for the induction of cytolysis of the pathological tissue. Liquid nitrogen can be applied to the wart using various devices, among which the most used are those that represent the dispensing of the product in the form of a spray. The duration of the application varies according to the lesion treated and in the media lasts a few seconds.

Verrutop®: solution based on Nitrizinc Complex®. This solution applied on the warts causes a change of colour (white-yellowish) and a hardening of the treated tissue ("mummification" process) favouring the renewal of the skin cells and the detachment of the wart. The treatment must be carried out by health personnel and takes place in the extraction of the product from a vial through a capillary and in the application of the same direct on the wart by direct contact.

At the time of enrollment, patients will be treated either with Verrutop® or with Cryotherapy. They will then be re-evaluated 10 days after the first treatment session and, in case of persistence of the lesions, another application will be carried out, for a maximum of four treatments. At the end of the four sessions, the experimenter will evaluate the response to the treatment; the evaluation includes three options:
1. Complete regression
2. Partial regression (reduction = or> 50% of the number of lesions)
3. No regression (<50% reduction in the number of lesions)

The tolerability of the two treatments will be assessed by both the investigator and the patient during and at the end of the study and will be expressed as good, moderate, poor after evaluation, at each follow-up visit, of 3 parameters:
1. Pain reported by the patient and defined as: mild 1 - moderate 2 - intense 3
2. Itching reported by the patient and defined as: mild 1 - moderate 2 - intense 3
3. Inflammation (observed by the doctor) and defined as: erythema: 1 - erosion: 2 - blisters: 3 - ulcer: 4

Only patients with complete injury regression will enter follow-up (T0), while patients with partial or absent regression will be referred to another conventional treatment. Follow-up visits will be carried out after 1 month (T1) and 3 months (T2) by T0. In the event of recurrence during follow-up, the patient will be referred to another conventional treatment.

Intervention type

Procedure/Surgery

Phase

Drug names

Primary outcome measure

At the end of the four sessions and again at three months, the experimenter will evaluate the response to the treatment; the evaluation includes three options:
1. Complete regression
2. Partial regression (reduction = or> 50% of the number of lesions)
3. No regression (<50% reduction in the number of lesions)

Secondary outcome measures

The tolerability of the two treatments will be assessed by both the investigator and the patient after every treatment session and at the end of the study and will be expressed as good, moderate, poor after evaluation, of 3 parameters:
1. Pain reported by the patient and defined as: mild 1 - moderate 2 - intense 3
2. Itching reported by the patient and defined as: mild 1 - moderate 2 - intense 3
3. Inflammation (observed by the doctor) and defined as: erythema: 1 - erosion: 2 - blisters: 3 - ulcer: 4

Overall trial start date

23/01/2017

Overall trial end date

01/11/2019

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. First episode never treated
2. Number of lesions: 3 to 10
3. Size of the single lesion: 1-5 mm
4. Location: penis/vulva/perianal region

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

120

Total final enrolment

120

Participant exclusion criteria

1. Previously treated patients
2. Circumcised patients
3. Immunosuppressed patients due to pathological and/or iatrogenic causes
4. Patients with diabetes mellitus
5. Pregnant women

Recruitment start date

01/12/2017

Recruitment end date

01/08/2019

Locations

Countries of recruitment

Italy

Trial participating centre

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Dermatology Unit Via Pace, 9
Milano
20122
Italy

Trial participating centre

Ospedale San Lazzaro
Medical Science Department Dermatologic Clinic University of Turin via Cherasco, 23
Turin
10126
Italy

Trial participating centre

Policlinico Sant'Orsola-Malpighi
Dermatology Unit Via Albertoni, 15
Bologna
40138
Italy

Sponsor information

Organisation

Isdin (Spain)

Sponsor details

Provençals 33
Barcelona
08019
Spain
(+34) 932 402 020
corinne.granger@isdin.com

Sponsor type

Industry

Website

https://www.isdin.com

Funders

Funder type

Industry

Funder name

ISDIN (Spain)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer-reviewed journal.

IPD sharing statement:
The datasets generated during and/or analysed during the current study are not expected to be made available due to privacy reasons. In particular data will be kept as hospital sensitive data in encrypted files accessible only to those who conducted the study. Maintained for 10 years and the data of each individual patient will never be made public.

Intention to publish date

01/04/2020

Participant level data

Not expected to be available

Basic results (scientific)

Publication list

2020 results in https://pubmed.ncbi.nlm.nih.gov/32734366/ (added 03/08/2020)

Publication citations

Additional files

Editorial Notes

03/08/2020: Publication reference and total final enrolment number added. 03/04/2020: Uploaded protocol (not peer reviewed) as an additional file. 24/03/2020: Trial’s existence confirmed by IRCCS Ospedale Maggiore Policlinico - Ca Granda Foundation.