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

Sponsor

Hospices Civils de Lyon (Other)

Overall Status

Completed

CT.gov ID

NCT01370798

Collaborator

(none)

244

Enrollment

Locations

Arms

75.8

Actual Duration (Months)

Patients Per Site

0.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hypospadias	Drug: promestriene Drug: Placebo Procedure: Urethroplasty Radiation: Wrist X ray Procedure: Blood test	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

244 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

May 26, 2011

Actual Primary Completion Date :

Sep 18, 2017

Actual Study Completion Date :

Sep 18, 2017

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: promestriene

Children with severe hypospadias treated with promestriene 1%

Drug: promestriene

Promestriene cream 1%, 1g per day during 2 months, cutaneous application

Procedure: Urethroplasty

Onlay-tube-onlay urethroplasty performed by a physician expert of this technique (at least 5 years of practical ability)

Radiation: Wrist X ray

Wrist X ray to follow the degree of bone maturation

Procedure: Blood test

Hormonal dosage: Oestradiol, testosterone, FSH-LH and AMH

Placebo Comparator: Placebo

Control group, children with severe hypospadias treated with Placebo.

Drug: Placebo

Placebo of promestriene cream, 1g per day during 2 months, cutaneous application

Procedure: Urethroplasty

Onlay-tube-onlay urethroplasty performed by a physician expert of this technique (at least 5 years of practical ability)

Radiation: Wrist X ray

Wrist X ray to follow the degree of bone maturation

Procedure: Blood test

Hormonal dosage: Oestradiol, testosterone, FSH-LH and AMH

Outcome Measures

Primary Outcome Measures

Number of patient with postoperative urethral fistula and dehiscence [1 year]

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

9 Months to 36 Months

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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)

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Service de Chirurgie Pédiatrique Uro-génitale, Hopital femme Mere Enfant	Bron Cedex	France	69677
2	Hôpital Mère-Enfant	Nantes	France	44093
3	Hôpital Robert Debré	Paris	France	72015
4	Hôpital NECKER	Paris	France	75015