Local Oestrogen Versus Placebo as Preoperative Treatment in Patients With Severe Hypospadias: Effects on Post-operative Complications

Study Overview
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Brief Summary
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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.

Official Title
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Local Oestrogen Versus Placebo as Preoperative Treatment in Patients With Severe Hypospadias: Effects on Post-operative Complications.

Conditions
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Hypospadias

Intervention / Treatment
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* Drug: promestriene
* Drug: Placebo
* Procedure: Urethroplasty
* Radiation: Wrist X ray
* Procedure: Blood test


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 9 Months
Maximum Age: 36 Months

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: promestriene<br>Children with severe hypospadias treated with promestriene 1% | Drug: promestriene<br>* Promestriene cream 1%, 1g per day during 2 months, cutaneous application<br>Procedure: Urethroplasty<br>* Onlay-tube-onlay urethroplasty performed by a physician expert of this technique (at least 5 years of practical ability)<br>Radiation: Wrist X ray<br>* Wrist X ray to follow the degree of bone maturation<br>Procedure: Blood test<br>* Hormonal dosage: Oestradiol, testosterone, FSH-LH and AMH<br>|
| Placebo Comparator: Placebo<br>Control group, children with severe hypospadias treated with Placebo. | Drug: Placebo<br>* Placebo of promestriene cream, 1g per day during 2 months, cutaneous application<br>Procedure: Urethroplasty<br>* Onlay-tube-onlay urethroplasty performed by a physician expert of this technique (at least 5 years of practical ability)<br>Radiation: Wrist X ray<br>* Wrist X ray to follow the degree of bone maturation<br>Procedure: Blood test<br>* Hormonal dosage: Oestradiol, testosterone, FSH-LH and AMH<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patient with postoperative urethral fistula and dehiscence |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Re-intervention related to wound healing | Number of re-interventions for fistula or dehiscence not related to stenosis, in the first year post surgery. | 1 year | 
| post-surgical complications | Total number and type of post-surgical complications | 1 year | 
| Re-intervention not related to wound healing | Number of re-interventions not related to wound healing | 1 year | 
| Hormone measurement | Plasmatic concentrations of Oestradiol, Testosterone, LH, FSH at inclusion and at 2 months (at the end of study treatment) | 2 months | 
| Bone age evaluation | Hand and wrist radiography at inclusion and 1 year after surgery. | 14 monthes | 
| Clinical tolerance of the treatment | Number and type of adverse events | 14 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Severe hypospadias, local oestrogen, promestriene, Onlay-tube-onlay urethroplasty, post-operative complications, fistula dehiscence