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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Hospices Civils de Lyon
Sponsor:
Information provided by (Responsible Party):
Hospices Civils de Lyon
ClinicalTrials.gov Identifier:
NCT01370798
First received: June 8, 2011
Last updated: July 7, 2014
Last verified: July 2014
  Purpose

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 Intervention Phase
Hypospadias
Drug: promestriene
Drug: Placebo
Procedure: Urethroplasty
Radiation: Wrist X ray
Procedure: Blood test
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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.

Resource links provided by NLM:


Further study details as provided by Hospices Civils de Lyon:

Primary Outcome Measures:
  • postoperative healing impairment [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Number of postoperative urethral fistula and dehiscence (of the reconstructed urethra) in the first year post surgery and not related to a postoperative urethral or meatus stenosis.


Secondary Outcome Measures:
  • Re-intervention related to wound healing [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Number of re-interventions for fistula or dehiscence not related to stenosis, in the first year post surgery.

  • post-surgical complications [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Total number and type of post-surgical complications

  • Re-intervention not related to wound healing [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Number of re-interventions not related to wound healing

  • Hormone measurement [ Time Frame: 2 months ] [ Designated as safety issue: Yes ]
    Plasmatic concentrations of Oestradiol, Testosterone, LH, FSH at inclusion and at 2 months (at the end of study treatment)

  • Bone age evaluation [ Time Frame: 14 monthes ] [ Designated as safety issue: Yes ]
    Hand and wrist radiography at inclusion and 1 year after surgery.

  • Clinical tolerance of the treatment [ Time Frame: 14 months ] [ Designated as safety issue: Yes ]
    Number and type of adverse events


Estimated Enrollment: 485
Study Start Date: May 2011
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   9 Months to 36 Months
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01370798

Contacts
Contact: Pierre Mouriquand, Prof +33 4 27 86 92 17 pierre.mouriquand@chu-lyon.fr
Contact: Daniela-Brindusa Gorduza, MD +33 4 27 86 92 17 daniela-brindusa.gorduza@chu-lyon.fr

Locations
France
Service de Chirurgie Pédiatrique Uro-génitale, Hopital femme Mere Enfant Recruiting
Bron Cedex, France, 69677
Contact: Pierre Mouriquand, Prof       pierre.mouriquand@chu-lyon.fr   
Principal Investigator: Pierre Mouriquand, Prof         
Sub-Investigator: Daniela-Brindusa Gorduza, MD         
Hôpital Mère-Enfant Recruiting
Nantes, France, 44093
Contact: MARC-DAVID LECLAIR, PR         
Principal Investigator: MARC-DAVID LECLAIR, PR         
Hôpital NECKER Recruiting
Paris, France, 75015
Contact: STEPHEN LORTAT JACOB, PR         
Principal Investigator: STEPHEN LORTAT JACOB, PR         
Hôpital Robert Debré Recruiting
Paris, France, 72015
Contact: EL GHONEIMI ALAA, PR         
Principal Investigator: ALAA EL GHONEIMI, PR         
Sponsors and Collaborators
Hospices Civils de Lyon
Investigators
Principal Investigator: Pierre Mouriquand, Prof HOPITAL FEMME MERE ENFANT CHU DE LYON
  More Information

No publications provided

Responsible Party: Hospices Civils de Lyon
ClinicalTrials.gov Identifier: NCT01370798     History of Changes
Other Study ID Numbers: 2010.608, 2010-023686-22
Study First Received: June 8, 2011
Last Updated: July 7, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Hospices Civils de Lyon:
Severe hypospadias
local oestrogen
promestriene
Onlay-tube-onlay urethroplasty
post-operative complications
fistula dehiscence

Additional relevant MeSH terms:
Penile Diseases
Postoperative Complications
Hypospadias
Pathologic Processes
Genital Diseases, Male
Urogenital Abnormalities
Congenital Abnormalities
Estrogens
Estradiol
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 25, 2014