Pehab Ii

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Participant type

Healthy volunteers, Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Male Urogenital Diseases [C12]

Trial duration

12 Jan 2024 → ongoing

Decision date (initial)

2023-12-08

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To determine the difference in rates of patients achieving good unassisted erections at 24 months of follow-up after receiving either 12 months of 75/100mg Sildenafil daily and VED therapy 5 times a week or 75/100mg Sildenafil on demand (≤3 times a week) as a penile rehabilitation program.

Secondary objectives 5

1.  Erectile Function: to evaluate time to- and percentage of patients in both arms in regaining unassisted and assisted erectile function sufficient for intercourse during follow-up in each rehabilitation arm. As well to assess and compare stretched penile length at 12 months compared to baseline.
2.  Health and sexual quality of life: To compare sexual function scores (i.e. orgasmic function), climacturia, feelings of masculinity, health-related quality of life, partner-interaction, between the treatment groups and between hetero versus gay/bisexual patients during follow-up.
3.  Adherence and side effects: To evaluate differences between the groups regarding adherence to the penile rehabilitation program, taking into account noted side effects and frequency of use of the prescribed treatment strategies.
4.  Best tool to evaluate erectile function: To evaluate differences in pre-operative IIEF-EF and EPIC-sexual domain scores between patients who are engaged in sexual intercourse and those that are not.
5.  Partners: to compare experiences with the program, sexual quality of life and partner-interaction from partners’ perspective between the treatment groups.

Conditions and MedDRA coding

Prostate cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. Pre-screening eligibility criteria: Age > 18 years and < 75 years
2. Inclusion criteria: A pre-diagnostic IIEF-EF>=22 with or without PDE5i. For patients without a partner or did not participate in penetrative sex we use accumulated score of EPIC- erectile function; Q8b, Q9 and Q10 >=83.
3. Inclusion criteria: Willing to provide blood samples to determine testosterone level, Hb1Ac, liver enzymes and lipid profile
4. Inclusion criteria: Testosterone levels of at least >9 nmol/l, measured pre or post-operative. Blood needs to be obtained before 11 am and before breakfast with the absence of hypo gonadal symptoms such as loss of libido, lack of energy and orgasmic dysfunction
5. Inclusion criteria: A signed informed consent form
6. Pre-screening eligibility criteria: Histologically confirmed PCa
7. Pre-screening eligibility criteria: Scheduled for RP as primary treatment with the intention of at least a one-sided nerve-sparing procedure.
8. Pre-screening eligibility criteria: Non-metastatic disease (cN0M0)
9. Pre-screening eligibility criteria: Pre-operative erections good enough for intercourse (anamnestic)
10. Pre-screening eligibility criteria: Motivated to participate in a penile rehabilitation program
11. Inclusion criteria: All of the above-mentioned pre-screening eligibility criteria
12. Inclusion criteria: At least unilateral nerve-sparing or if available FP score =>5
13. Inclusion criteria: A pre-diagnostic anamnestic erection that was good enough for intercourse.
14. Pre-screening eligibility criteria: Patients who have a penis that has developed naturally, without surgical interventions.

Exclusion criteria 6

1. Exclusion criteria: Adjuvant radiotherapy or hormonal therapy
2. Exclusion criteria: Inability to use VED such as severe penile deformity or too much peripubic, or belly fat causing fitting problems
3. Exclusion criteria: All of the above-mentioned pre-screening exclusion criteria
4. Pre-screening exclusion criteria: Regarding history of oncological treatment  Previous pelvic radiation therapy  Patients on Androgen Deprivation Therapy (ADT)  Patients with diseases that affect the red blood cells (e.g., sickle cell anaemia), blood cancer (leukaemia) or bone marrow tumors
5. Pre-screening exclusion criteria: Regarding history of cardiovascular diseases  Patients with heart failure New York Heart Association (NYHA) ≥ class 3  Patients with increased susceptibility to vasodilators include those with left ventricular outflow obstruction (e.g., aortic stenosis, hypertrophic obstructive cardiomyopathy), or those with the rare syndrome of multiple system atrophy manifesting as severely impaired autonomic control of blood pressure.  Patients with unstable angina pectoris  Patients using nitride oxide for coronary artery disease  Patients with hypotension (blood pressure <90/50 mmHg)  Patients with recent (within the last 6 months) history of stroke (CVA or TIA) or myocardial infarction  Patients with diseases that affect blood clotting or causes bleeding (i.e. coagulation disorders) or prolonged erections  Patients with a severe renal impairment (creatinine clearance <30 mL/min)  Patients with hepatic impairment (cirrhosis)
6. Pre-screening exclusion criteria: Other pre-screening exclusion criteria:  Patients with other neurological diseases; such as Parkinson and polyneuropathy.  Allergy regarding Sildenafil  Patients who have loss of vision in one eye because of non-arteritic anterior ischaemic optic neuropathy (NAION), regardless of whether this episode was in connection or not with previous PDE5 inhibitor exposure.  Patients with severe hepatic impairment  Patients with known hereditary degenerative retinal disorders such as retinitis pigmentosa (a minority of these patients have genetic disorders of retinal phosphodiesterases).  Patients using alpha-blockers, but they may be eligible to participate after discontinuing alpha-blocker use.  The inability to speak and read in Dutch

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. To evaluate the rates of return to adequate spontaneous unassisted erections at 24 months after nerve-sparing radical prostatectomy (nsRP) following a 12-month program of either daily sildenafil (75/100mg) and vacuum erection device (VED) therapy five times a week or Sildenafil(75/100mg) on-demand (≤3 times a week).

Secondary endpoints 10

1. Erectile function endpoints:  The return to baseline erection rate 24 months after nsRP according to the IIEF-EF or EPIC-erection function and EHS, comparing two different penile rehabilitation programmes.
2. Erectile function endpoints:  The time to recovery of erectile function using IIEF-EF or EPIC-erection function and EHS, comparing two different penile rehabilitation programmes.
3. Erectile function endpoints:  The rates of achieving good unassisted erections at 18 months according to IIEF-EF or EPIC-erection function and EHS, comparing two different penile rehabilitation programmes.
4. Erectile function endpoints:  The rate of patients achieving good assisted erections at 6, 9, 12, and 18 months according to IIEF-EF or EPIC-erection function and EHS, comparing two different penile rehabilitation programs. The stretched penile length at 12 months compared to baseline.
5. Health related and sexual quality of life endpoints:  Other sexual function scores (i.e. orgasmic function), feelings of masculinity and health-related quality of life scores between the treatment groups and between hetero versus gay/bisexual patients over time. Using IIEF-15 domains, EPIC-sexual domain, QLQC30, PRP-25 and two self-composed masculinity and gay/bisexual inventory at baseline, 12 months and 24 months.
6. Health related and sexual quality of life endpoints:  The effects of climacturia between the groups. Using a self- designed questionnaire based on validated questionnaires. Measurements will take place 12 months and 24 months after surgery.
7. Health related and sexual quality of life endpoints:  The partner interaction between the treatment groups. Using a self-designed questionnaire based on validated questionnaires. At baseline, 12 months and 24 months.
8. Adherence and side effects endpoints:  The adherence to the penile rehabilitation programs during the first 12 months of follow-up. Taking into account noted side effects and frequency of use of the prescribed treatment strategies. Using a self-de- signed questionnaire based on validated questionnaires.
9. Best tool to evaluate erectile function endpoint:  The pre-operative IIEF-EF and EPIC-sexual domain scores between patients who are engaged in sexual intercourse and those who are not.
10. Partner endpoints:  Satisfaction with rehabilitation program from partners’ perspective at 12 months and 24 months.  The partner interaction between the treatment groups from partners’ perspective. Using a self-designed questionnaire based on validated questionnaires at baseline and 24 months after surgery.  Sexual health related quality of life scores of partners between the different treatment groups. Using EORTC QLQ-SH22 at baseline at 12 months and 24 months after surgery.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Sponsor organisation

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Address

Plesmanlaan 121

City

Amsterdam

Postcode

1066 CX

Country

Netherlands

Scientific contact point

Organisation

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Contact name

M.P.J. Nicolai

Public contact point

Organisation

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Contact name

M.P.J. Nicolai

Locations

1 EU/EEA country · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 21 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications