Hypospadias
Conditions
Keywords
hypospadias
Brief summary
The primary objective of this study is to determine the efficacy of administering a course of postoperative oral steroids in pediatric patients undergoing proximal hypospadias repair as prevention against complications. Specifically, the study aims to assess if the steroids i) decrease the incidence of wound breakdown, fistula formation, stenosis or stricture formation, and the need for subsequent redo-hypospadias surgeries and/or fistula repairs and ii) improve the quality of wound healing including the overall cosmetic appearance of the phallus (i.e. location of the urethral meatus).
Detailed description
Hypospadias repair is a surgery that is, unfortunately, fraught with a high complication rate with problems that include urethrocutaneous fistula formation, complete wound breakdown, glans dehiscence, urethral diverticulum formation, retraction of the urethral meatus, urethral stricture, and meatal stenosis . Failure of a proximal hypospadias repair (i.e. the development of a post-operative complication) is unpredictable, and few modifiable risk factors having been identified. Complications necessitate subsequent surgical intervention for pediatric patients, which must be carried out under general anesthesia. Evidence regarding the harms of multiple general anesthetics for children is increasing. Additionally, with each surgical revision comes the morbidity associated with another post-surgical convalescence. Thus, any measure that can be gained as a way to increase the rate of success of proximal hypospadias repair would be of help to all pediatric urologists and patients with hypospadias. The proposed intervention of administering a 5 day course of placebo versus oral steroids at a dose equivalent to what is given for outpatient treatment of asthma exacerbations, is expected to have very low risk. This would be the only variation from the current practice and one that has never been studied in the past. Thus, it would be worthwhile to perform use scientific methods to determine if the administration of a short course of oral steroids is of benefit to healing and minimization of post-operative complications for hypospadias patients.
Interventions
DRUGPrednisolone
In order to analyze the data, we will establish a chart which will show the degree of cosmetic appearance, incidences and degree of complications. This we be assessed on a mild to severe scale.
In order to analyze the data, we will establish a chart which will show the degree of cosmetic appearance, incidences and degree of complications. This we be assessed on a mild to severe scale.
Sponsors
Francis Schneck
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
3 Months to 22 Years
Healthy volunteers
Yes
Inclusion criteria
* Patients undergoing proximal hypospadias repair
Exclusion criteria
* All patients currently taking steroids at the time of surgery or during the six-week recovery period as well as patients with betamethasone hypersensitivity will be excluded from the study. Selection will be based on parent willingness to allow the child to participate in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complication Rate After Hypospadias Repair | postoperative follow up 7-12 days after the surgery following completion of the 5-day course of prednisolone vs. placebo. | Post-operative incidence of wound breakdown, fistula formation, stenosis or stricture formation, and the need for subsequent redo-hypospadias surgeries and/or fistula repairs, after Hypospadias repair. |
| Meatus Location After Hypospadias Repair | postoperative follow up 7-12 days after the surgery following completion of the 5-day course of prednisolone vs. placebo. | The overall cosmetic appearance of the phallus (i.e. location of the urethral meatus) post-operatively. |
| Improvement of Chordee After Hypospadias Repair | postoperative follow up 7-12 days after the surgery following completion of the 5-day course of prednisolone vs. placebo. | Improvement of Chordee post-operatively after Hypospadias repair. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complications After Hypospadias Repair | 6 months after surgery | 6-month follow-up incidence of wound breakdown, fistula formation, stenosis or stricture formation, and the need for subsequent redo-hypospadias surgeries and/or fistula repairs, after Hypospadias repair. |
| Meatus Location After Hypospadias Repair | 6-months after surgery | The overall cosmetic appearance of the phallus (i.e. location of the urethral meatus) 6 months post-operatively. |
| Healing Outcomes After Hypospadias Repair, Follow up After Toilet Training | Approximately at 4 years of age | i) the incidence of wound breakdown, fistula formation, stenosis or stricture formation, and the need for subsequent redo-hypospadias surgeries and/or fistula repairs and ii) the quality of wound healing including improvement of Chordee, and the overall cosmetic appearance of the phallus (i.e. location of the urethral meatus). Late complications can occur. Therefore, this needs to be evaluated at the specified interval. This is the standard of care at Children's Hospital of Pittsburgh of UPMC Pediatric Urology department. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Oral Steroids Systemic high-dose steroids (30 mg/kg methylprednisolone) have been shown in a randomized, double-blind, placebo-controlled trial in humans not to negatively impact wound infection or dehiscence rates, instead benefitting patients in the postoperative period in ways such as decreasing pain. An acute course of oral systemic steroids has been routinely used in patients under the age of 12 with asthma exacerbations (liquid prednisolone at 1-2 mg/kg/day in 1-2 divided doses for up to 10 days, although usually given for 5 days, which is at least 19 times less than the dose proven to be safe in the randomized controlled trial mentioned above) and proven to be safe without adverse effects. Effect of prednisolone on the systemic response and wound healing after colonic surgery.
Prednisolone: In order to analyze the data, we will establish a chart which will show the degree of cosmetic appearance, incidences and degree of complications. This we be assessed on a mild to severe scale. | 17 |
| Placebo-controlled Simple Syrup will be used as the placebo
placebo-controlled: In order to analyze the data, we will establish a chart which will show the degree of cosmetic appearance, incidences and degree of complications. This we be assessed on a mild to severe scale. | 11 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | patients did not report compliance | 4 | 1 |
| Overall Study | Protocol Violation | 1 | 0 |
Baseline characteristics
| Characteristic | Oral Steroids | Placebo-controlled | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 17 Participants | 11 Participants | 28 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Incidence of Comorbidities | 6 Participants | 5 Participants | 11 Participants |
| NICU Stay | 11 Participants | 5 Participants | 16 Participants |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment United States | 17 participants | 11 participants | 28 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 17 Participants | 11 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 11 |
| other Total, other adverse events | 0 / 17 | 0 / 11 |
| serious Total, serious adverse events | 0 / 17 | 0 / 11 |
Outcome results
Primary
Complication Rate After Hypospadias Repair
Post-operative incidence of wound breakdown, fistula formation, stenosis or stricture formation, and the need for subsequent redo-hypospadias surgeries and/or fistula repairs, after Hypospadias repair.
Time frame: after stent removal at 4-12 weeks
Population: Further statistical analyses were not conducted on the data due to insufficient enrollment and follow-up participation, resulting in study termination.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Oral Steroids | Complication Rate After Hypospadias Repair | meatal retraction | 1 Participants |
| Oral Steroids | Complication Rate After Hypospadias Repair | meatal stenosis | 0 Participants |
| Oral Steroids | Complication Rate After Hypospadias Repair | glans dehiscence | 0 Participants |
| Oral Steroids | Complication Rate After Hypospadias Repair | skin breakdown along suture lines, urethra intact | 0 Participants |
| Oral Steroids | Complication Rate After Hypospadias Repair | urethra breakdown proximal to glans | 0 Participants |
| Oral Steroids | Complication Rate After Hypospadias Repair | urethrocutaneous fistula | 2 Participants |
| Oral Steroids | Complication Rate After Hypospadias Repair | suspected stricture | 0 Participants |
| Oral Steroids | Complication Rate After Hypospadias Repair | suspected urethral diverticulum | 0 Participants |
| Placebo-controlled | Complication Rate After Hypospadias Repair | suspected urethral diverticulum | 0 Participants |
| Placebo-controlled | Complication Rate After Hypospadias Repair | meatal retraction | 0 Participants |
| Placebo-controlled | Complication Rate After Hypospadias Repair | urethra breakdown proximal to glans | 0 Participants |
| Placebo-controlled | Complication Rate After Hypospadias Repair | meatal stenosis | 0 Participants |
| Placebo-controlled | Complication Rate After Hypospadias Repair | suspected stricture | 0 Participants |
| Placebo-controlled | Complication Rate After Hypospadias Repair | glans dehiscence | 1 Participants |
| Placebo-controlled | Complication Rate After Hypospadias Repair | urethrocutaneous fistula | 0 Participants |
| Placebo-controlled | Complication Rate After Hypospadias Repair | skin breakdown along suture lines, urethra intact | 0 Participants |
Primary
Complication Rate After Hypospadias Repair
Post-operative incidence of wound breakdown, fistula formation, stenosis or stricture formation, and the need for subsequent redo-hypospadias surgeries and/or fistula repairs, after Hypospadias repair.
Time frame: postoperative follow up 7-12 days after the surgery following completion of the 5-day course of prednisolone vs. placebo.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Oral Steroids | Complication Rate After Hypospadias Repair | meatal retraction | 1 Participants |
| Oral Steroids | Complication Rate After Hypospadias Repair | meatal stenosis | 0 Participants |
| Oral Steroids | Complication Rate After Hypospadias Repair | glans dehiscence | 0 Participants |
| Oral Steroids | Complication Rate After Hypospadias Repair | skin breakdown along suture lines, urethra intact | 0 Participants |
| Oral Steroids | Complication Rate After Hypospadias Repair | urethra breakdown proximal to glans | 0 Participants |
| Oral Steroids | Complication Rate After Hypospadias Repair | urethrocutaneous fistula | 2 Participants |
| Oral Steroids | Complication Rate After Hypospadias Repair | suspected stricture | 0 Participants |
| Oral Steroids | Complication Rate After Hypospadias Repair | suspected urethral diverticulum | 1 Participants |
| Placebo-controlled | Complication Rate After Hypospadias Repair | suspected urethral diverticulum | 0 Participants |
| Placebo-controlled | Complication Rate After Hypospadias Repair | meatal retraction | 0 Participants |
| Placebo-controlled | Complication Rate After Hypospadias Repair | urethra breakdown proximal to glans | 0 Participants |
| Placebo-controlled | Complication Rate After Hypospadias Repair | meatal stenosis | 0 Participants |
| Placebo-controlled | Complication Rate After Hypospadias Repair | suspected stricture | 0 Participants |
| Placebo-controlled | Complication Rate After Hypospadias Repair | glans dehiscence | 1 Participants |
| Placebo-controlled | Complication Rate After Hypospadias Repair | urethrocutaneous fistula | 0 Participants |
| Placebo-controlled | Complication Rate After Hypospadias Repair | skin breakdown along suture lines, urethra intact | 0 Participants |
Comparison: Due to the number of 0 cell counts, it is not possible to do individual statistics for each complication, so we looked at the incidence of complications overall between the two arms.p-value: <0.62Fisher Exact
Primary
Improvement of Chordee After Hypospadias Repair
Improvement of Chordee post-operatively after Hypospadias repair.
Time frame: postoperative follow up 7-12 days after the surgery following completion of the 5-day course of prednisolone vs. placebo.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Oral Steroids | Improvement of Chordee After Hypospadias Repair | improvement of chordee with degloving | not described | 3 Participants |
| Oral Steroids | Improvement of Chordee After Hypospadias Repair | improvement in ventral chordee | no improvement | 5 Participants |
| Oral Steroids | Improvement of Chordee After Hypospadias Repair | improvement of chordee with degloving | improved | 3 Participants |
| Oral Steroids | Improvement of Chordee After Hypospadias Repair | improvement in ventral chordee | not described | 8 Participants |
| Oral Steroids | Improvement of Chordee After Hypospadias Repair | improvement in ventral chordee | resolved | 2 Participants |
| Oral Steroids | Improvement of Chordee After Hypospadias Repair | improvement of chordee with plication | resolved | 7 Participants |
| Oral Steroids | Improvement of Chordee After Hypospadias Repair | improvement of chordee with degloving | no improvement | 8 Participants |
| Oral Steroids | Improvement of Chordee After Hypospadias Repair | improvement of chordee with plication | improved | 1 Participants |
| Oral Steroids | Improvement of Chordee After Hypospadias Repair | improvement in ventral chordee | improved | 2 Participants |
| Oral Steroids | Improvement of Chordee After Hypospadias Repair | improvement of chordee with plication | improvement described but not documented | 0 Participants |
| Oral Steroids | Improvement of Chordee After Hypospadias Repair | improvement of chordee with degloving | improvement described but not documented | 1 Participants |
| Oral Steroids | Improvement of Chordee After Hypospadias Repair | improvement of chordee with plication | no improvement | 0 Participants |
| Oral Steroids | Improvement of Chordee After Hypospadias Repair | improvement in ventral chordee | improvement described but not documented | 0 Participants |
| Oral Steroids | Improvement of Chordee After Hypospadias Repair | improvement of chordee with plication | not described | 9 Participants |
| Oral Steroids | Improvement of Chordee After Hypospadias Repair | improvement of chordee with degloving | resolved | 2 Participants |
| Placebo-controlled | Improvement of Chordee After Hypospadias Repair | improvement of chordee with plication | not described | 4 Participants |
| Placebo-controlled | Improvement of Chordee After Hypospadias Repair | improvement of chordee with degloving | resolved | 2 Participants |
| Placebo-controlled | Improvement of Chordee After Hypospadias Repair | improvement of chordee with degloving | improved | 1 Participants |
| Placebo-controlled | Improvement of Chordee After Hypospadias Repair | improvement of chordee with degloving | improvement described but not documented | 0 Participants |
| Placebo-controlled | Improvement of Chordee After Hypospadias Repair | improvement of chordee with degloving | no improvement | 7 Participants |
| Placebo-controlled | Improvement of Chordee After Hypospadias Repair | improvement of chordee with degloving | not described | 1 Participants |
| Placebo-controlled | Improvement of Chordee After Hypospadias Repair | improvement in ventral chordee | resolved | 0 Participants |
| Placebo-controlled | Improvement of Chordee After Hypospadias Repair | improvement in ventral chordee | improved | 2 Participants |
| Placebo-controlled | Improvement of Chordee After Hypospadias Repair | improvement in ventral chordee | improvement described but not documented | 0 Participants |
| Placebo-controlled | Improvement of Chordee After Hypospadias Repair | improvement in ventral chordee | no improvement | 2 Participants |
| Placebo-controlled | Improvement of Chordee After Hypospadias Repair | improvement in ventral chordee | not described | 7 Participants |
| Placebo-controlled | Improvement of Chordee After Hypospadias Repair | improvement of chordee with plication | resolved | 6 Participants |
| Placebo-controlled | Improvement of Chordee After Hypospadias Repair | improvement of chordee with plication | improved | 1 Participants |
| Placebo-controlled | Improvement of Chordee After Hypospadias Repair | improvement of chordee with plication | improvement described but not documented | 0 Participants |
| Placebo-controlled | Improvement of Chordee After Hypospadias Repair | improvement of chordee with plication | no improvement | 0 Participants |
Comparison: Improvement category: Chordee with Deglovingp-value: <0.87Fisher Exact
Comparison: Improvement category: Ventral Chordeep-value: <0.64Fisher Exact
Comparison: Improvement category: Chordee with Plicationp-value: <0.85Fisher Exact
Primary
Meatus Location After Hypospadias Repair
Post operative follow-up after stent removal at 4-12 weeks of the overall cosmetic appearance of the phallus (i.e. location of the urethral meatus).
Time frame: after stent removal at 4-12 weeks
Population: Further statistical analyses were not conducted on the data due to insufficient enrollment and follow-up participation, resulting in study termination.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Oral Steroids | Meatus Location After Hypospadias Repair | other | 0 Participants |
| Oral Steroids | Meatus Location After Hypospadias Repair | glanular | 9 Participants |
| Oral Steroids | Meatus Location After Hypospadias Repair | coronal | 1 Participants |
| Oral Steroids | Meatus Location After Hypospadias Repair | subcoronal | 0 Participants |
| Oral Steroids | Meatus Location After Hypospadias Repair | distal shaft | 0 Participants |
| Oral Steroids | Meatus Location After Hypospadias Repair | proximal shaft | 0 Participants |
| Oral Steroids | Meatus Location After Hypospadias Repair | penoscrotal | 3 Participants |
| Placebo-controlled | Meatus Location After Hypospadias Repair | other | 0 Participants |
| Placebo-controlled | Meatus Location After Hypospadias Repair | distal shaft | 0 Participants |
| Placebo-controlled | Meatus Location After Hypospadias Repair | glanular | 8 Participants |
| Placebo-controlled | Meatus Location After Hypospadias Repair | penoscrotal | 2 Participants |
| Placebo-controlled | Meatus Location After Hypospadias Repair | coronal | 1 Participants |
| Placebo-controlled | Meatus Location After Hypospadias Repair | proximal shaft | 0 Participants |
| Placebo-controlled | Meatus Location After Hypospadias Repair | subcoronal | 0 Participants |
Primary
Meatus Location After Hypospadias Repair
The overall cosmetic appearance of the phallus (i.e. location of the urethral meatus) post-operatively.
Time frame: postoperative follow up 7-12 days after the surgery following completion of the 5-day course of prednisolone vs. placebo.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Oral Steroids | Meatus Location After Hypospadias Repair | subcoronal | 0 Participants |
| Oral Steroids | Meatus Location After Hypospadias Repair | proximal shaft | 0 Participants |
| Oral Steroids | Meatus Location After Hypospadias Repair | coronal | 0 Participants |
| Oral Steroids | Meatus Location After Hypospadias Repair | penoscrotal | 4 Participants |
| Oral Steroids | Meatus Location After Hypospadias Repair | distal shaft | 0 Participants |
| Oral Steroids | Meatus Location After Hypospadias Repair | other | 0 Participants |
| Oral Steroids | Meatus Location After Hypospadias Repair | glanular | 13 Participants |
| Placebo-controlled | Meatus Location After Hypospadias Repair | other | 1 Participants |
| Placebo-controlled | Meatus Location After Hypospadias Repair | glanular | 8 Participants |
| Placebo-controlled | Meatus Location After Hypospadias Repair | coronal | 0 Participants |
| Placebo-controlled | Meatus Location After Hypospadias Repair | subcoronal | 0 Participants |
| Placebo-controlled | Meatus Location After Hypospadias Repair | distal shaft | 0 Participants |
| Placebo-controlled | Meatus Location After Hypospadias Repair | proximal shaft | 0 Participants |
| Placebo-controlled | Meatus Location After Hypospadias Repair | penoscrotal | 2 Participants |
p-value: <0.61Fisher Exact
Secondary
Complications After Hypospadias Repair
6-month follow-up incidence of wound breakdown, fistula formation, stenosis or stricture formation, and the need for subsequent redo-hypospadias surgeries and/or fistula repairs, after Hypospadias repair.
Time frame: 6 months after surgery
Population: Further statistical analyses were not conducted on the data due to insufficient enrollment and follow-up participation, resulting in study termination.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Oral Steroids | Complications After Hypospadias Repair | meatal retraction | 0 Participants |
| Oral Steroids | Complications After Hypospadias Repair | meatal stenosis | 0 Participants |
| Oral Steroids | Complications After Hypospadias Repair | glans dehiscence | 0 Participants |
| Oral Steroids | Complications After Hypospadias Repair | skin breakdown along suture lines, urethra intact | 0 Participants |
| Oral Steroids | Complications After Hypospadias Repair | urethra breakdown proximal to glans | 0 Participants |
| Oral Steroids | Complications After Hypospadias Repair | urethrocutaneous fistula | 2 Participants |
| Oral Steroids | Complications After Hypospadias Repair | suspected stricture | 0 Participants |
| Oral Steroids | Complications After Hypospadias Repair | suspected urethral diverticulum | 1 Participants |
| Placebo-controlled | Complications After Hypospadias Repair | suspected urethral diverticulum | 0 Participants |
| Placebo-controlled | Complications After Hypospadias Repair | meatal retraction | 0 Participants |
| Placebo-controlled | Complications After Hypospadias Repair | urethra breakdown proximal to glans | 0 Participants |
| Placebo-controlled | Complications After Hypospadias Repair | meatal stenosis | 0 Participants |
| Placebo-controlled | Complications After Hypospadias Repair | suspected stricture | 0 Participants |
| Placebo-controlled | Complications After Hypospadias Repair | glans dehiscence | 0 Participants |
| Placebo-controlled | Complications After Hypospadias Repair | urethrocutaneous fistula | 1 Participants |
| Placebo-controlled | Complications After Hypospadias Repair | skin breakdown along suture lines, urethra intact | 0 Participants |
Secondary
Healing Outcomes After Hypospadias Repair, Follow up After Toilet Training
i) the incidence of wound breakdown, fistula formation, stenosis or stricture formation, and the need for subsequent redo-hypospadias surgeries and/or fistula repairs and ii) the quality of wound healing including improvement of Chordee, and the overall cosmetic appearance of the phallus (i.e. location of the urethral meatus). Late complications can occur. Therefore, this needs to be evaluated at the specified interval. This is the standard of care at Children's Hospital of Pittsburgh of UPMC Pediatric Urology department.
Time frame: Approximately at 4 years of age
Population: The study was terminated prior to the 4 year follow up due to lack of sufficient patient data to analyze; therefore, there was no post-toilet training follow up data collected.
Secondary
Meatus Location After Hypospadias Repair
The overall cosmetic appearance of the phallus (i.e. location of the urethral meatus) 6 months post-operatively.
Time frame: 6-months after surgery
Population: Further statistical analyses were not conducted on the data due to insufficient enrollment and follow-up participation, resulting in study termination.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Oral Steroids | Meatus Location After Hypospadias Repair | subcoronal | 0 Participants |
| Oral Steroids | Meatus Location After Hypospadias Repair | proximal shaft | 0 Participants |
| Oral Steroids | Meatus Location After Hypospadias Repair | coronal | 0 Participants |
| Oral Steroids | Meatus Location After Hypospadias Repair | penoscrotal | 3 Participants |
| Oral Steroids | Meatus Location After Hypospadias Repair | distal shaft | 0 Participants |
| Oral Steroids | Meatus Location After Hypospadias Repair | other | 0 Participants |
| Oral Steroids | Meatus Location After Hypospadias Repair | glanular | 4 Participants |
| Placebo-controlled | Meatus Location After Hypospadias Repair | other | 0 Participants |
| Placebo-controlled | Meatus Location After Hypospadias Repair | glanular | 1 Participants |
| Placebo-controlled | Meatus Location After Hypospadias Repair | coronal | 1 Participants |
| Placebo-controlled | Meatus Location After Hypospadias Repair | subcoronal | 0 Participants |
| Placebo-controlled | Meatus Location After Hypospadias Repair | distal shaft | 0 Participants |
| Placebo-controlled | Meatus Location After Hypospadias Repair | proximal shaft | 0 Participants |
| Placebo-controlled | Meatus Location After Hypospadias Repair | penoscrotal | 1 Participants |