Back to resultsLocal Oestrogen Versus Placebo as Preoperative Treatment in Patients With Severe Hypospadias: Effects on Post-operative Complications (HYPOSPADES)
Primary Purpose
Hypospadias
Status
Completed
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
promestriene
Placebo
Urethroplasty
Wrist X ray
Blood test
Sponsored by
About this trial
This is an interventional prevention trial for Hypospadias focused on measuring Severe hypospadias, local oestrogen, promestriene, Onlay-tube-onlay urethroplasty, post-operative complications, fistula dehiscence
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)
Sites / Locations
- Service de Chirurgie Pédiatrique Uro-génitale, Hopital femme Mere Enfant
- Hôpital Mère-Enfant
- Hôpital Robert Debré
- Hôpital NECKER
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
promestriene
Placebo
Arm Description
Children with severe hypospadias treated with promestriene 1%
Control group, children with severe hypospadias treated with Placebo.
Outcomes
Primary Outcome Measures
Number of patient with postoperative urethral fistula and dehiscence
Secondary Outcome Measures
Re-intervention related to wound healing
Number of re-interventions for fistula or dehiscence not related to stenosis, in the first year post surgery.
post-surgical complications
Total number and type of post-surgical complications
Re-intervention not related to wound healing
Number of re-interventions not related to wound healing
Hormone measurement
Plasmatic concentrations of Oestradiol, Testosterone, LH, FSH at inclusion and at 2 months (at the end of study treatment)
Bone age evaluation
Hand and wrist radiography at inclusion and 1 year after surgery.
Clinical tolerance of the treatment
Number and type of adverse events
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01370798
Brief Title
Local Oestrogen Versus Placebo as Preoperative Treatment in Patients With Severe Hypospadias: Effects on Post-operative Complications
Acronym
HYPOSPADES
Official Title
Local Oestrogen Versus Placebo as Preoperative Treatment in Patients With Severe Hypospadias: Effects on Post-operative Complications.
Study Type
Interventional
2. Study Status
Record Verification Date
July 2018
Overall Recruitment Status
Completed
Study Start Date
May 26, 2011 (Actual)
Primary Completion Date
September 18, 2017 (Actual)
Study Completion Date
September 18, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospices Civils de Lyon
4. Oversight
Data Monitoring Committee
Yes
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypospadias
Keywords
Severe hypospadias, local oestrogen, promestriene, Onlay-tube-onlay urethroplasty, post-operative complications, fistula dehiscence
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
244 (Actual)
8. Arms, Groups, and Interventions
Arm Title
promestriene
Arm Type
Experimental
Arm Description
Children with severe hypospadias treated with promestriene 1%
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Control group, children with severe hypospadias treated with Placebo.
Intervention Type
Drug
Intervention Name(s)
promestriene
Intervention Description
Promestriene cream 1%, 1g per day during 2 months, cutaneous application
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo of promestriene cream, 1g per day during 2 months, cutaneous application
Intervention Type
Procedure
Intervention Name(s)
Urethroplasty
Intervention Description
Onlay-tube-onlay urethroplasty performed by a physician expert of this technique (at least 5 years of practical ability)
Intervention Type
Radiation
Intervention Name(s)
Wrist X ray
Intervention Description
Wrist X ray to follow the degree of bone maturation
Intervention Type
Procedure
Intervention Name(s)
Blood test
Intervention Description
Hormonal dosage: Oestradiol, testosterone, FSH-LH and AMH
Primary Outcome Measure Information:
Title
Number of patient with postoperative urethral fistula and dehiscence
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Re-intervention related to wound healing
Description
Number of re-interventions for fistula or dehiscence not related to stenosis, in the first year post surgery.
Time Frame
1 year
Title
post-surgical complications
Description
Total number and type of post-surgical complications
Time Frame
1 year
Title
Re-intervention not related to wound healing
Description
Number of re-interventions not related to wound healing
Time Frame
1 year
Title
Hormone measurement
Description
Plasmatic concentrations of Oestradiol, Testosterone, LH, FSH at inclusion and at 2 months (at the end of study treatment)
Time Frame
2 months
Title
Bone age evaluation
Description
Hand and wrist radiography at inclusion and 1 year after surgery.
Time Frame
14 monthes
Title
Clinical tolerance of the treatment
Description
Number and type of adverse events
Time Frame
14 months
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
9 Months
Maximum Age & Unit of Time
36 Months
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pierre Mouriquand, Prof
Organizational Affiliation
HOPITAL FEMME MERE ENFANT CHU DE LYON
Official's Role
Principal Investigator
Facility Information:
Facility Name
Service de Chirurgie Pédiatrique Uro-génitale, Hopital femme Mere Enfant
City
Bron Cedex
ZIP/Postal Code
69677
Country
France
Facility Name
Hôpital Mère-Enfant
City
Nantes
ZIP/Postal Code
44093
Country
France
Facility Name
Hôpital Robert Debré
City
Paris
ZIP/Postal Code
72015
Country
France
Facility Name
Hôpital NECKER
City
Paris
ZIP/Postal Code
75015
Country
France
12. IPD Sharing Statement
Citations:
PubMed Identifier
32386308
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.
Results Reference
derived
Learn more about this trial
Local Oestrogen Versus Placebo as Preoperative Treatment in Patients With Severe Hypospadias: Effects on Post-operative Complications
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