Clinical trial NCT01370798: Local Oestrogen Versus Placebo as Preoperative Treatment in Patients With Severe Hypospadias: Effects on Post-operative Complications
Official title: Local Oestrogen Versus Placebo as Preoperative Treatment in Patients With Severe Hypospadias: Effects on Post-operative Complications.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypospadias
Keywords: Severe hypospadias
local oestrogen
promestriene
Onlay-tube-onlay urethroplasty
post-operative complications
fistula dehiscence
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2011-06-10
Enrollment: 244
Sex: MALE
Minimum age (years): 9
Maximum age (years): 36
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Hypospadias is a congenital abnormality of the penis that is caused by incomplete development of the anterior urethra. This pathology is one of the most common genital anomalies in paediatric urology .The incidence is reported to be 1 out of 250 live male births and is increasing regularly. The hypospadias surgeries present a high risk of post operative complications requiring re-interventions.

A great part of the post operative complications is related to imperfect healing issues. If androgen stimulation seems to be deleterious, at the opposite, oestrogen could impact positively on the skin healing process. This point leads to the hypothesis that local transcutaneous oestrogen stimulation on the ventral and dorsal penile faces decreases the number of skin healing post-operative defects.

The objective of the study is to assess the effect of oestrogen (applied once daily for 2 months prior to surgery) on the post-operative complications.


Eligibility criteria: Inclusion Criteria:

* Severe hypospadias with a division of the corpus spongiosum behind the midshaft of the penis and for which repair requires a urethral substitution by onlay urethroplasty.
* Subjects operated between 9 and 36 months old.
* Subjects operated in one of the departments of paediatric urology involved in the study.
* Surgery performed by a surgeon with at least 5 years of practical experience in the hypospadias surgery.
* Written informed consent obtained from parents or legal guardians prior to the participation to the study
* All hypospadias aetiology (hormonal, karyotype or genetic)

Exclusion Criteria:

* Refusal to participate
* Subjects with glandular hypospadias
* Subjects aged \<9 months or \> 36months old at time of surgery.
* Subjects who had prior surgery of penis (circumcision or hypospadias surgery)
* Subjects treated with androgens (Human Chorionic Gonadotrophin or delayed testosterone) within 6 months prior to surgery.
* Intolerance to promestriene or its excipients.
* Not affiliated to a healthy or social security cover.
* Known tumoral risk
* Pure or mixed gonadal dysgenesis (45, X0/46,XY)

Primary outcomes:
measure: Number of patient with postoperative urethral fistula and dehiscence
timeFrame: 1 year
Secondary outcomes:
measure: Re-intervention related to wound healing
timeFrame: 1 year
measure: post-surgical complications
timeFrame: 1 year
measure: Re-intervention not related to wound healing
timeFrame: 1 year
measure: Hormone measurement
timeFrame: 2 months
measure: Bone age evaluation
timeFrame: 14 monthes
measure: Clinical tolerance of the treatment
timeFrame: 14 months
Other outcomes:
Locations:
city: Bron Cedex
country: France
facility: Service de Chirurgie Pédiatrique Uro-génitale, Hopital femme Mere Enfant
city: Nantes
country: France
facility: Hôpital Mère-Enfant
city: Paris
country: France
facility: Hôpital Robert Debré
city: Paris
country: France
facility: Hôpital NECKER
Study officials:
affiliation: HOPITAL FEMME MERE ENFANT CHU DE LYON
name: Pierre Mouriquand, Prof
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gorduza D, Plotton I, Remontet L, Gay CL, El Jani M, Cheikhelard A, Blanc T, El Ghoneimi A, Leclair MD, Roy P, Pirot F, Mimouni Y, Gaillard S, Chatelain P, Morel Y, Kassai B, Mouriquand P. Preoperative Topical Estrogen Treatment vs Placebo in 244 Children With Midshaft and Posterior Hypospadias. J Clin Endocrinol Metab. 2020 Jul 1;105(7):dgaa231. doi: 10.1210/clinem/dgaa231.