Interest of early erectile rehabilitation with Sildenafil after proctectomy for rectal cancer : Randomized controlled trial (RECTIL)
- Conditions
- Men treated with proctectomy for rectal cancer
- Registration Number
- 2024-515431-30-00
- Lead Sponsor
- Centre Hospitalier Universitaire Rouen
- Brief Summary
The main objective is to evaluate the efficacy of erectile rehabilitation with Sildenafil after proctectomy in the prevention of long-term erectile dysfunction at 12 months post-operatively
- Detailed Description
Colorectal cancer is the third most common cancer in men in France, after lung and prostate cancer. Proctectomy (possibly preceded by radiotherapy) is the most effective treatment for this cancer, but erectile dysfunction (ED) is a frequent complication, even when the nerves are preserved during dissection, and has a major impact on the quality of life of operated men.
The cause of erectile dysfunction after rectal cancer surgery is usually neurological, due to intraoperative trauma to the autonomic nerves, while erectile dysfunction after radiotherapy is mainly vascular in origin, with damage to erectile tissue.
Several risk factors for sexual dysfunction after rectal cancer surgery have been reported (age, neoadjuvant radiotherapy, type of resection, operative difficulties and complications, body image affected by protective stoma). On the other hand, surgical expertise may be a protective factor.
In the physiological condition, the nitric oxide released by the pelvic nerves causes an increase in cyclic guanosine monophosphate, which in turn causes smooth muscle cells relaxation and an influx of blood into the cavernous body, triggering and maintaining the erection.
Similar to prostatectomy, nerve damage can occur during proctectomy through stretching, heat, ischemia or inflammation; this nerve damage results in reduced nitric oxide production.
Even in the absence of nerve damage, it has been demonstrated (in an animal model) that post-operative neurapraxia is responsible for the at least temporary disappearance of spontaneous and nocturnal erections, leading to cavernous hypoxia. This is followed by tissue changes (reduction in smooth and elastic muscle fibers in the corpora cavernosa, increase in collagen and endothelial dysfunction), which modify the hemodynamics of the carvernum body and ultimately lead to fibrosis of the erectile tissue.
These changes can become permanent despite subsequent nerve recovery, and are exacerbated by neoadjuvant radiotherapy. It is therefore important not to wait passively for erectile function to be restored, as lack of oxygenation to the corpora cavernosa can lead to permanent fibrosis and dysfunction.
This physiopathology is at the origin of the concept of erectile rehabilitation after prostatectomy, with the aim of maintain erections post-operatively and thus limiting fibrosis.
The benefits of erectile re-education after prostatectomy were first reported in 1997, with the early use of intracavernous injections of alprostadil. Following this study, various rehabilitation strategies have been recommended. Early treatment, i.e. within the first month, is recommended to promote cavernous oxygenation and prevent fibrosis.
The aims of rehabilitation are as follows :
* limit fibrosis;
* limit penis retraction and loss of height;
* oxygenate the cavernum body;
* preserve endothelial structure;
* preserve smooth muscle cell structure.
Various types of rehabilitation have been proposed: oral PDE-5 inhibitors, intra-cavernosal injections, urethral suppositories or vaccum.
PDE-5 inhibitors prevent the degradation of cyclic guanosine monophosphate, thus compensating for the reduction in nitric oxide and enabling a better erection.
Erectile rehabilitation using PDE-5 inhibitors could protect cavernous smooth muscle from irreversible pathophysiological changes. The basic concept is to administer a PDE-5 inhibitor at bedtime to facilitate nocturnal erections, which are thought to have a natural protective effect on the function of the cavernous bodies.
Padma-Nathan et al. reported the prospective administration of sildenafil 50 and 100 mg vs. placebo, daily and at bedtime, in patients undergoing nerve-sparing radical prostatectomy. After 36 weeks, erectile function was significantly better in the sildenafil group, with 27% responders, vs. 4% in the placebo group.
The mechanisms involved in erectile dysfunction after proctectomy for rectal cancer are similar to those of radical prostatectomy for prostate cancer.
The efficacy of PDE-5 inhibitors in the treatment of erectile dysfunction after proctectomy has already been demonstrated. However, its use as a preventive measure has rarely been reported.
Three studies have evaluated PDE-5 inhibitors in patients with erectile dysfunction after rectal resection, two of which used sildenafil (Viagra, Pfizer, New York, NY)
To our knowledge, only one study has evaluated the role of PDE-5 inhibitors (PDE-5i) in a preventive strategy.
Originality and innovation Despite the fact that sexual dysfunction is recognized as a frequent complication of rectal cancer treatment, there are currently no recommendations for its prevention and management.
In contrast to prostate cancer patients, information and treatment concerning erectile dysfunction (ED) are not systematically offered to men with colorectal cancer. The ability of sildenafil to facilitate the return of erections after radical prostatectomy has been demonstrated in several studies, and this treatment could benefit patients treated for rectal cancer.
To date, no randomized study has examined the usefulness of this early rehabilitation in patients managed for rectal cancer. This study proposes, for the first time, to evaluate the use of sildenafil after neo-adjuvant radiotherapy and surgery for rectal cancer.
Recruitment & Eligibility
- Status
- Authorised, recruitment pending
- Sex
- Male
- Target Recruitment
- 188
Men aged 18 to 70 years
Patients undergoing surgery for cancer of the lower or middle rectum by total removal of the mesorectum with colorectal or coloanal anastomosis 30 days ago (+/- 7 days) and with normal preoperative erectile function (defined as a combined IIEF erectile function domain score of at least 22)
Sexually active patient without treatment for erectile function prior to surgery
Presence of a stable sexual partner (male or female)
Adult who has read and understood the information letter and signed the consent form
Membership in a social security plan
Conservative nerve surgery
T4 tumor or requiring an enlarged surgery
History of prostate cancer
Contraindication to SILDENAFIL EG 50 mg, film-coated tablet: - Cardiovascular disease (history of heart failure, myocardial infarction, angina, arrhythmia, aortic stenosis, or hypertrophic obstructive cardiomyopathy) except controlled hypertension - Recent history of stroke - Hypotension (blood pressure < 90/50 mmHg) - Severe hepatic insufficiency - Severe renal insufficiency (creatinine clearance less than 30 ml/min) - Uncontrolled diabetes (hemoglobin A1C >12%) - Bleeding disorders or active peptic ulcer - Anatomical malformation of the penis (angulation, fibrosis of the corpora cavernosa or Peyronie's disease) - Patients with conditions that may predispose them to priapism (such as sickle cell disease, multiple myeloma or leukemia) - Patients with loss of vision in one eye due to non-arteritic anterior ischemic optic neuropathy (NOIAN) - Known degenerative hereditary retinal disorders such as retinitis pigmentosa, - Drug combinations contraindicating sildenafil (o cytochrome P450 inhibitors (ritonavir), CYP3A4 inhibitors (ketoconazole, itraconazole, erythromycin, clarithromycin, cimetidine, saquinavir, ritonavir, saquinavir and grapefruit juice) o nitric oxide donors (such as the amyl nitrite sold over the counter in sex shops ("poppers") or nitro derivatives in any form (trinitrine or isosorbide mono or dinitrate, sodium nitroprusside; linsidomine, molsidomine, nicorandil). Such combinations are dangerous for life. - alpha-blockers (prazosin, urapidil) - guanylate cyclase stimulators, such as riociguat) - Hypersensitivity to the active substance or to one of the excipients - Allergy to peanuts or soy
Sleep disorder, patients taking sedatives/hypnotics
Patients with abnormal erectile function defined by a combined IIEF erectile function domain score of less than 22
Contraindication to Placebo : Allergy to one of its components (polyethylene glycol 3350, starch) Treatment with polyethylene glycol (macrogol: forlax, transipeg)
Patients already treated with PDE5 inhibitors
Patients with SARS COV 2* * In accordance with the general measures required to deal with the Covid-19 epidemic, as set out in an order issued by the Minister of Solidarity and Health, the diagnostic test(s) used to detect SARS-CoV-2 must be included in the list published on the website of the Ministry of Solidarity and Health, available at the following address: https://covid-19.sante.gouv.fr/tests".
Person deprived of liberty by an administrative or judicial decision or person placed under safeguard of justice / sub-guardianship or curatorship
History of psychological or sensory illness or abnormality that could affect the subject's ability to understand the conditions required for participation in the protocol or to give informed consent.
Person participating in another drug trial
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Primary Outcome Measures
Name Time Method Patient response at 12 months post-operatively. A patient is defined as a responder by a score of at least 22 on the erectile function domain of the International Index of Erectile Function (IIEF), which includes the six questions of the IIEF related to erection (Q1-Q5 and Q15) Patient response at 12 months post-operatively. A patient is defined as a responder by a score of at least 22 on the erectile function domain of the International Index of Erectile Function (IIEF), which includes the six questions of the IIEF related to erection (Q1-Q5 and Q15)
- Secondary Outcome Measures
Name Time Method IIEF erectile function domain score combining the six IIEF questions related to erection (Q1-Q5 and Q15) measured at surgery, D0, M3, M6 and M9 postoperative IIEF erectile function domain score combining the six IIEF questions related to erection (Q1-Q5 and Q15) measured at surgery, D0, M3, M6 and M9 postoperative
International Index of Erectile Function global score measured at surgery, D0, M3, M6, M9 and M12 postoperative International Index of Erectile Function global score measured at surgery, D0, M3, M6, M9 and M12 postoperative
Quality of life score (EORTC QLQ - C30 and QLQ - CR29) measured at surgery, D0, M3, M6, M9 and M12 postoperative Quality of life score (EORTC QLQ - C30 and QLQ - CR29) measured at surgery, D0, M3, M6, M9 and M12 postoperative
LARS score measured at surgery, D0, M3, M6, M9 and M12 postoperative LARS score measured at surgery, D0, M3, M6, M9 and M12 postoperative
Fecal Continence Score (Wexner score) measured at surgery, D0, M3, M6, M9 and M12 postoperative Fecal Continence Score (Wexner score) measured at surgery, D0, M3, M6, M9 and M12 postoperative
The number of patients presenting spontaneous erections under treatment at M3, M6, M9 postoperative and without treatment at D0, and M12 postoperative. The number of patients presenting spontaneous erections under treatment at M3, M6, M9 postoperative and without treatment at D0, and M12 postoperative.
The number of patients with or without regular psychological followup. A patient is defined as having regular follow-up if he visits a psychologist and/or psychiatrist once or twice a month The number of patients with or without regular psychological followup. A patient is defined as having regular follow-up if he visits a psychologist and/or psychiatrist once or twice a month
Number of unused tablets during the study. The patient will be considered as non-compliant if tablet intake over the entire 10 months of treatment is < 80%. Number of unused tablets during the study. The patient will be considered as non-compliant if tablet intake over the entire 10 months of treatment is < 80%.
The number of AEs and SAEs in each group at D0, M3, M6, M9 and M12 postoperative The number of AEs and SAEs in each group at D0, M3, M6, M9 and M12 postoperative
Trial Locations
- Locations (13)
Centre Hospitalier Universitaire De Caen Normandie
🇫🇷Caen Cedex 9, France
Centre Hospitalier Universitaire De Lille
🇫🇷Lille Cedex, France
Institut Paoli Calmettes
🇫🇷Marseille, France
Centre Hospitalier Universitaire Amiens Picardie
🇫🇷Amiens, France
Bordeaux Colorectal Institute Academy
🇫🇷Le Bouscat, France
Bicetre Hospital
🇫🇷Le Kremlin Bicetre Cedex, France
Centre Hospitalier Simone Veil De Beauvais
🇫🇷Beauvais, France
CHU Besancon
🇫🇷Besancon, France
Hopital Saint Antoine
🇫🇷Paris Cedex 12, France
Assistance Publique Hopitaux De Paris
🇫🇷Paris, France
Scroll for more (3 remaining)Centre Hospitalier Universitaire De Caen Normandie🇫🇷Caen Cedex 9, FranceArnaud ALVESSite contact0231063221alves-a@chu-caen.fr