Dr. Michele Spinelli
Neuro-Urology Service, Unipolar Spinal Unit
Piazza dell’Ospedale Maggiore 3
20162, Milano, Italy
Dr. Gianluca Sampogna
Neuro-Urology Service, Unipolar Spinal Unit
Piazza dell’Ospedale Maggiore 3
20162, Milano, Italy
|Title||Safety and efficacy of inflatable penile prostheses in people with spinal cord injury|
|Study Center||Neuro-Urology Service, Unipolar Spinal Unit, Niguarda Hospital
Piazza dell’Ospedale Maggiore 3, 20162, Milano, Italy
|Investigators||PI: Dr. Michele Spinelli – Co-Pi: Dr. Gianluca Sampogna|
|Study Design||Prospective case series|
|Study Duration||24 months [Start date: June 1st, 2021 – End date: May 31st, 2023]|
|Number of Subjects||15|
|Primary Study Aim||To evaluate the safety and efficacy of inflatable penile prostheses in people with spinal cord injury|
|Type of Penile Prostheses||Inflatable penile prostheses by Coloplast™|
|Patient Population||Inclusion criteria:
· Male adults with spinal cord dysfunction/injury
· Erectile dysfunction not responding to pharmacological therapy and/or vacuum erection devices
· Pre-operative Erection Hardness Score ≤ 2 (penis is not hard enough for penetration)
· Optimal bladder and bowel management to reduce the risks of infections
· Consent and compliance with all aspects of the study protocol and with providing requested data during follow-up
· Age < 18 years
· Penile erections which are valid for penetration with or without any pharmacological therapy and/or vacuum erection devices
· Inappropriate bladder and/or bowel management
· Active infections anywhere in the body, especially urinary tract or genital infections
· Patient’s documented sensitivity to prosthesis materials
· Unwillingness to undergo any further surgery for device revision
|Study Endpoints||Primary endpoints:
· To evaluate safety of inflatable penile prostheses in people with spinal cord dysfunction/injury in terms of intra- and post-operative complications within the considered follow-up period
· To evaluate efficacy of inflatable penile prostheses in people with spinal cord dysfunction/injury (i.e., achievement of penile erections to allow sexual intercourses)
· To assess the change from baseline to follow-up visits of Erection Hardness Scores and results of specific questionnaires validated internationally and evaluating quality of life and sacral functions
· To establish a safe and effective workflow to implant inflatable penile prostheses in people with spinal cord dysfunction/injury to favor their diffusion among frail people
|Follow-up Duration||12 months for each patient|
|Follow-up Protocol||Follow-up schedule: 14 days, 4 weeks, 2 months, 3 months, 6 months, 9 months, and 12 months
Follow-up visit evaluations:
· Physical examination
· Assessment for adverse events and/or complications following surgery
· Current medications and/or novel comorbidities diagnosed since the last visit
· Erection Hardness Score
· Sexual diary, 3-day bladder diary and 7-day bowel diary filled in during the period since the last visit
· Questionnaires validated internationally and assessing sacral functions and related quality of life (IIEF-5, Qualiveen-30, ICIQ-UI, and MENTOR Tool)
· Subjective evaluations based on a 10-point Likert scale assessing patient satisfaction and suggestion of this treatment to other people
|Statistical Methodology||Descriptive and inferential analysis of all collected pre-, intra- and post-operative data|
The implant of penile prosthesis (PP) is an effective and safe treatment option for men with erectile dysfunction (ED).1,2 However, this surgery may be associated with a higher risk of complications in certain populations: diabetes, significant corporal fibrosis, concurrent continence surgery, complex salvage cases, and spinal cord dysfunction/injury (SCD/I).3 Indeed, SCD/I is usually referred as a contraindication to PP implant because of the increased risk of complications. This limit is based upon dated studies, which do not consider recent changes.4,5,6,7
Technology advancements (e.g. Bioflex® material, hydrophilic coating), surgical technique refinements and strict protocols during pre- and post-operative phases have improved the clinical outcomes over the years.8,9
Moreover, the epidemiology of spinal cord injured people has changed with a significant increase of people with incomplete lesions, associated with an improved trophism and a partial residual sensitivity at the level of external genitalia, which may address prompt clinical evaluation in case of need and reduce the risk of prosthesis extrusion.10
The above-mentioned conditions pave the way for novel studies assessing the safety and efficacy of new-generation inflatable PPs (IPPs) in SCD/I.
This study is aimed to evaluate the safety and efficacy of IPP in individuals with SCD/I.
- To evaluate the safety of IPP in people with SCD/I in terms of intra- and post-operative complications within the considered follow-up period
- To evaluate the efficacy of IPP in people with SCD/I to achieve penile erections and allow sexual intercourses
- To evaluate changes from baseline to follow-up visits of Erection Hardness Score
- To evaluate changes in results of specific questionnaires (see the section Pre-Operative Exams) validated internationally and assessing quality of life and sacral functions
- To describe a safe and effective workflow to implant IPPs in people with SCD/I to favor their diffusion among frail people
A multidisciplinary team is the key for the study success. The investigators have individuated a series of specialists, who have worked with them over the years and have agreed to participate in this study.
The following professional figures will be involved:
- Expert surgeon consultant (Dr. Stefano Fiordelise, website: andrologopiacenza.com), who has a long-standing experience in IPP management, and will help the investigators during pre- and post-operative patient evaluations, surgical procedures and complication management;
- Anesthesiologist with a specific expertise in the clinical management of individuals with SCD/I;
- Physiatrist to perform counselling for evaluation and optimization of patients’ rehabilitation programs (e.g., to improve hand function for IPP activation);
- Gastroenterologist specialized in neurogenic bowel dysfunction for pre-operative and follow-up bowel assessment, as an inappropriate bowel management is a key source of urinary tract infections;11
- Occupational therapist with expertise in SCD/I for the pre- and post-operative counseling to enhance used aids (e.g., development of wheelchair cushions to reduce the pressure at the level of external genitalia reducing the risk of IPP extrusion);
- Psychiatrist to exclude/reduce psychological issues negatively impacting sex life and, in general, quality of life;
- Nurses during the surgical procedures and outpatient visits with a long-lasting experience in the management of SCD/I.
Besides healthcare professionals, the investigators will hire a Data Manager to help and organize the entire activity, and to collect all data for statistical analysis, especially the results of the administered questionnaires.
Conflicts of Interest
None of study personnel has conflicts of interest to declare.
Materials and Methods
Prospective case series.
The study will be conducted by the Neuro-Urology Service, Unipolar Spinal Unit, Niguarda Hospital, Milano, Italy, which represent a tertiary referral center for SCD/I with a valuable clinical, research and academic activity. By the Niguarda Hospital, the patient may benefit from the expertise of many high-level specialties; indeed, this center has been considered the best Italian hospital according to the annual list delivered by Newsweek (available at: https://www.newsweek.com/best-hospitals-2020/italy). Over the years, a specific know-how has been gained concerning SCD/I to deliver patient-tailored solutions about clinical management, 360-degree rehabilitation programs and aids (e.g., patient-specific wheelchairs). Moreover, the considered center has established a long-lasting relationship with Coloplast™ over the years, specially for the development and evaluation of trans-anal irrigation through the Peristeen™ device.
The study will start on June 1st, 2021, and last for twenty-four (24) months, up to May 31st, 2023.
During the first twelve (12) months, the investigators will enroll the patients and perform surgical procedures. From June 1st, 2022, the investigators will proceed to complete the follow-up, ensuring at least 12 months of follow-up for each patient enrolled.
The study might be closed before the planned end date in specific cases, reported in the section Reasons for Study Withdrawal or Termination.
We will include male adults with SCD/I presenting the following characteristics:
- ED not responding to pharmacological therapy and/or vacuum erection devices;
- Pre-operative Erection Hardness Score ≤ 2 (i.e., penis is hard, but not hard enough for penetration);
- Optimal bladder and bowel management, assessed by urological and gastroenterological evaluations to reduce infection risks;
- Consent and compliance with all aspects of the study protocol and with providing requested data during follow-up.
The following criteria will determine the patient exclusion:
- Age < 18 years;
- Penile erections which are valid for penetration with or without any pharmacological therapy and/or vacuum erection devices;
- Inappropriate bladder and/or bowel management, assessed after urological and gastroenterological evaluations;
- Active infections anywhere in the body, especially urinary tract and genital infections;
- Patient documented sensitivity to IPP materials;
- Unwillingness to undergo any further surgery for device revision.
All patients will undergo an in-depth andrological evaluation. Physical examination will exclude diseases (e.g., phimosis, Peyronie’s disease, penile cancer) requiring other surgery rather than PP implant. The investigators will assess Erection Hardness Score and IIEF-5 in each patient, besides performing penile Doppler ultrasound (US).12
The bladder management will be defined as “optimal” by the involved urologists after excluding signs and/or symptoms of urinary incontinence, macrohematuria, difficulties performing clean intermittent catheterizations, recurrent urinary tract and/or male accessory gland infections. To assess urinary incontinence impact, the investigators will adopt specific questionnaires validated in Italian and for self-administration, like the Qualiveen-30 and the ICIQ-UI.13,14 Before surgery, each case will complete a 3-day voiding diary and undergo genitourinary US and videourodynamics to exclude conditions undermining the IPP-related outcomes (e.g., significant neurogenic detrusor overactivity, vesico-ureteral reflux, bladder stones), requiring further treatments.
The bowel management will be assessed by the involved gastroenterologist using an objective decision-making tool, supported by Coloplast and called the MENTOR tool.15 According to this tool, only patients associated with a “green light” will be characterized by an appropriate bowel management and addressed to IPP surgery. The gastroenterologist will also consider patients’ 7-day bowel diaries for their evaluations.
Pre-operative exams will include cell blood count, renal function (creatinine, sodium, potassium, chloride, calcium), coagulation tests, inflammatory indices (c-reactive protein and procalcitonin), urine culture and rectal swab.
We will administer the following antimicrobials from 48 hours before the surgery and for at least 7 days: Vancomicin, Piperacillin/Tazobactam (PIP/TAZ), and Fluconazole. The above-mentioned antimicrobials could be changed according to the result of patients’ urine cultures and rectal swabs.
The day before the surgery, all cases will undergo trichotomy and abdominal radiography to confirm an appropriate bowel emptying.
By our center, the adaption of a similar long-course intravenous antibiotic treatment and an appropriate bowel emptying before the procedure has significantly decreased the rate of urinary tract infections after reno-ureteral stone surgery in frail people with SCD/I.
The investigators will implant the IPPs following the best scientific evidence available about the penoscrotal approach.16 Surgery will be performed under the supervision of an expert surgeon consultant. We are going to use the IPPs by Coloplast™. All types (Titan™, Titan Touch™) will be implanted according to patients and surgeons’ preferences. We will select the appropriate length and girth intraoperatively. The operative time usually last from 90 to 150 minutes.
The antimicrobials, Vancomicin, PIP/TAZ, and fluconazole, will be continued up to – at least – the 4th post-operative day. Painkillers (e.g., paracetamole, acetylsalicylic acid, and ibuprofen) will be administered continuously for 2 weeks and once per day for further 2 weeks after surgery to reduce the risks of life-threatening dysautonomic crises, which are common and often misdiagnosed surgical complications in people with SCD/I.
Patients will be discharged on the 4th post-operative day in absence of fever (body temperature > 37.8 °C), pain, bleeding, and complications. Otherwise, the hospital stay will last up to the resolution of fever (after at least 24 hours without antimicrobials), pain, and complications.
The IPP will not be activated (inflated) during hospital stay for the first time, but at an office visit once the swelling has decreased; this usually occurs after one month.
Potential Benefits and Expected Outcomes
People with SCD/I report sexual issues as ones of the most important in terms of quality of life.17 Therefore, a definitive solution for neurogenic ED is advocated by many individuals with SCD/I and involved professional figures.
The acquired know-how could be applied not only to people with SCD/I, but also to old and frail individuals, who represent an increasing population all over the world.
Risks to Patients
Studies published previously assessing PPs in SCD/I reported a higher incidence of complications in this population. Indeed, PPs are usually contraindicated in case of unresolved problems affecting urination, such as an elevated residual urine volume secondary to bladder outlet obstruction or neurogenic bladder. This scientific evidence was collected decades ago under different conditions, as reported in the section Background. Each patient will be deeply informed about the increased risk of complications compared to the general population, especially infections and device erosions. After the discussion, the patient should sign the informed consent before enrollment. If the patient is unwilling to undergo any further surgery for device revision, he will be promptly excluded.
During the hospital stay, each complication will be promptly assessed and treated in a multi-specialty center with a significant know-how concerning SCD/I acquired over the years. Many studies conducted in a multi-disciplinary setting by our hospital have outlined the advantages of a tertiary referral center to treat the specific challenges of individuals with SCD/I.18
In case of complications after discharge, the Niguarda Hospital has the most important Emergency Room in our region and may receive the enrolled cases, allowing a direct consultation of the investigators. Otherwise, the investigators are available to perform televisits with patients and teleconsults with specialists where the patients refer to. Indeed, the investigators have pioneered telehealth in SCD/I (see CVs).
The investigators will discuss each case with the expert surgeon consultant and other involved professional figures to evaluate the adverse event and plan the appropriate treatment.
After surgery, the investigators will perform follow-up visits at 14 days, 4 weeks, 2 months, 3 months, 6 months, 9 months, and 12 months.
During each follow-up visit the investigators will evaluate the following features:
- Physical examination;
- Adverse events and/or complications following surgery;
- Current medications and/or novel comorbidities diagnosed since the last visit;
- Erection Hardness Score;
- Sexual diary;
- Bladder diary of 3 days;
- Bowel diary of 7 days;
- Specific questionnaires assessing quality of life and all sacral functions (IIEF-5, Qualiveen-30, ICIQ-UI, and MENTOR tool);
- Subjective evaluations based on a 10-point Likert scale assessing patient satisfaction and suggestion of this treatment to other people.
The following procedures will be performed if the subject presents to the clinic at any other time point not specified above:
- Physical examination;
- Assessment for adverse events and complications following treatments;
- Evaluation of all current medications, including over-the-counter and herbal medications;
- Assessment of novel comorbidities diagnosed since the last visit.
Reasons for Study Withdrawal or Termination
A subject may be discontinued from the study at any time if the subject, the investigators, or the sponsors feel that it is not in the subject’s best interest to continue.
The following is a list of possible reasons for study treatment discontinuation:
- Screening failure;
- Subject withdrawal of consent;
- Subject is not compliant with study procedures;
- Adverse event that in the opinion of the investigators would be in the best interest of the subject to discontinue study participation;
- Protocol violation requiring discontinuation;
- Lost to follow-up;
- Request by Coloplast™ for early termination of study;
- Request by the Niguarda Hospital for early termination of study;
- Subject death;
- Difficulties with enrollment due to patients’ unwillingness and/or specialists’ contraindications;
- 12-month follow-up completed for all cases in advance.
The investigators will perform descriptive and inferential analysis of all pre-, intra- and post-operative data: e.g., age at surgery, type of SCD/I, years since SCD/I, neurological level, operative time, estimated blood loss, adverse events, intra- and post-operative complications, changes in pre- and post-operative Erection Hardness Scores or adopted questionnaire results.
The small enrolled sample will not allow extensive inferential statistics, even if the published data will be shared to enable systematic review and meta-analyses, besides representing an initial database to expand and implement in the future by the investigators themselves.
The investigators certify that all applicable institutional and governmental regulations concerning the ethical use of human volunteers will be followed during the course of this research. In particular, the study will be conducted following all prescriptions reported by the Declaration of Helsinki and Good Clinical Practice (GCP), an international quality standard for clinical trials involving human subjects. Before the study initiation, the investigators will ask for the approval of the Institutional Review Board (IRB) of the Niguarda Hospital, submitting all the relevant documentation, including study protocol, IPP specifications, and case report forms, to obtain a transparent opinion.
Patients’ data will be treated following the General Data Protection Regulation (GDPR) 2016/679, which is a regulation on data protection and privacy in the European Union (EU) and the European Economic Area (EEA). Therefore, all sensitive data will be stored in a pseudo-anonymized way and presented in an aggregate way to avoid tracing back to the patient. The responsible of patients’ privacy will be the Principal Investigator.
The Principal Investigator will also collect all regulatory documents of this study and correspondences among Coloplast™ and the Niguarda Hospital.
Clinical trial insurance will cover all study phases according to international regulations and national laws.
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- Saavedra-Belaunde JA, Clavell-Hernandez J, Wang R. Epidemiology regarding penile prosthetic surgery. Asian J Androl. 2020;22(1):2-7. doi: 10.4103/aja.aja_124_19
- Chung E. Penile prosthesis implant in the special populations: diabetics, neurogenic conditions, fibrotic cases, concurrent urinary continence surgery, and salvage implants. Asian J Androl. 2019;21:1-6. doi:10.4103/aja.aja
- Kimoto Y, Iwatsubo E. Penile prostheses for the management of the neuropathic bladder and sexual dysfunction in spinal cord injury patients: long term follow up. Paraplegia. 1994;32(5):336-9. doi: 10.1038/sc.1994.57
- Jaworski TM, Richards JS, Lloyd LK. Retrospective review of sexual and marital satisfaction of spinal cord injury and diabetic males post penile injection or implant. Urology. 1992;40(2):127-31. doi: 10.1016/0090-4295(92)90510-4
- Zermann DH, Kutzenberger J, Sauerwein D, Schubert J, Loeffler U. Penile prosthetic surgery in neurologically impaired patients: long-term followup. J Urol. 2006;175(3 Pt 1):1041-4; discussion 1044. doi: 10.1016/S0022-5347(05)00344-7
- Kim YD, Yang SO, Lee JK, Jung TY, Shim HB. Usefulness of a malleable penile prosthesis in patients with a spinal cord injury. Int J Urol. 2008;15(10):919-23. doi: 10.1111/j.1442-2042.2008.02115.x
- Scherzer ND, Dick B, Gabrielson AT, Alzweri LM, Hellstrom WJG. Penile Prosthesis Complications: Planning, Prevention, and Decision Making. Sex Med Rev. 2019;7(2):349-359. doi: 10.1016/j.sxmr.2018.04.002
- Hebert KJ, Kohler TS. Penile Prosthesis Infection: Myths and Realities. World J Mens Health. 2019;37(3):276-287. doi: 10.5534/wjmh.180123
- Ferro S, Cecconi L, Bonavita J, Pagliacci MC, Biggeri A, Franceschini M. Incidence of traumatic spinal cord injury in Italy during 2013-2014: a population-based study. Spinal Cord. 2017;55(12):1103-1107. doi: 10.1038/sc.2017.88
- Malykhina AP, Wyndaele JJ, Andersson KE, De Wachter S, Dmochowski RR. Do the urinary bladder and large bowel interact, in sickness or in health? ICI-RS 2011. Neurourol Urodyn. 2012;31(3):352‐358. doi:10.1002/nau.21228
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- Emmanuel A, Krogh K, Kirshblum S, Christensen P, Spinelli M, van Kuppevelt D, Abel R, Leder D, Santacruz BG, Bain K, Passananti V. Creation and validation of a new tool for the monitoring efficacy of neurogenic bowel dysfunction treatment on response: the MENTOR tool. Spinal Cord. 2020;58(7):795-802. doi: 10.1038/s41393-020-0424-8
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Sampogna G, Maltagliati M, Rocco B, Micali S, Montanari E, Spinelli M. Shock wave lithotripsy for a renal stone in a tetraplegic patient as a trigger for life-threatening posterior reversible encephalopathy syndrome. Urol Case Rep. 2020;31:101204. doi: 10.1016/j.e