Evaluation of Sildenafil for Early Erectile Rehabilitation Post-Proctectomy in Rectal Cancer: A Randomized Controlled Trial

The primary objective of this study is to evaluate the efficacy of early **erectile rehabilitation** with Sildenafil in preventing long-term erectile dysfunction in men who have undergone proctectomy for rectal cancer. This is clinically relevant as erectile dysfunction is a common complication following proctectomy, impacting the quality of life and psychological well-being of patients.

Secondary objectives include:

• Evaluating erectile function, sexual function, quality of life, digestive function, and anal continence at the time of surgery and 30 days post-surgery.
• Assessing the effectiveness of Sildenafil on erectile and sexual function at 3, 6, 9, and 12 months post-surgery.
• Determining the impact of Sildenafil on the quality of life, digestive function, and fecal incontinence at 3, 6, 9, and 12 months post-surgery.
• Evaluating the number of patients achieving spontaneous erection under treatment and without treatment at various time points post-surgery.
• Investigating whether the combination of psychological support with Sildenafil improves sexual function.
• Assessing treatment compliance and the frequency and severity of adverse events.

The clinical trial involves **men** who have undergone a **proctectomy** for rectal cancer, specifically targeting those aged 18 to 70 years. The study population is exclusively male, with participants having undergone surgery for cancer of the lower or middle rectum by total removal of the mesorectum with colorectal or coloanal anastomosis approximately 30 days prior to the trial. Participants are required to have had normal preoperative erectile function, defined by a combined IIEF erectile function domain score of at least 22, and must be sexually active without prior treatment for erectile dysfunction. Additionally, participants must have a stable sexual partner, have read and understood the information letter, signed the consent form, and be members of a social security plan. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants in the study.

The clinical trial is designed to evaluate the efficacy of **sildenafil** in the prevention of long-term erectile dysfunction following proctectomy for rectal cancer. This is a randomized, controlled trial with a double-blind design, ensuring that neither the participants nor the researchers know who is receiving the active treatment or the placebo. The trial is expected to commence recruitment on April 1, 2025, and conclude by April 1, 2028. Participants will be involved in the study for a maximum of 12 months, with the treatment period lasting up to 10 months.

Study visits are structured to include an initial screening visit, where eligibility is confirmed based on criteria such as age, surgical history, and preoperative erectile function. Following the screening, participants will be randomized to receive either **sildenafil** or a placebo. Follow-up visits are scheduled at surgery, Day 0 (D0), and at 3, 6, 9, and 12 months postoperatively. These visits aim to assess the primary endpoint, which is the erectile function domain score of the International Index of Erectile Function (IIEF) at 12 months. Secondary endpoints include various scores related to erectile function, quality of life, fecal continence, and psychological follow-up, measured at specified intervals throughout the study.

Participants are expected to adhere to the study protocol, with compliance monitored through the number of unused tablets. Non-compliance is defined as tablet intake below 80% over the treatment period. Conditions that may lead to early termination from the study include significant adverse events or serious adverse events, as well as non-compliance with the study protocol. The trial's design and procedures are meticulously structured to ensure the collection of robust and reliable data, contributing to the understanding of erectile rehabilitation post-proctectomy.

The clinical trial involves the administration of **Sildenafil EG 50 mg**, a **film-coated tablet** containing the active substance **sildenafil**. This medication is chemically derived and is intended for **oral use**. The dosage is set at 50 mg per day, with a maximum treatment period of 10 days. The total maximum dose that can be administered over the course of the treatment is 15,208 mg. The primary objective of this trial is to assess the efficacy of sildenafil in the early rehabilitation of erectile function following proctectomy for rectal cancer. Compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the treatment protocol.

The study also includes a **placebo** group, which will receive a **placebo de Sildenafil EG 50 mg**, designed to mimic the appearance of the active medication but without any active pharmaceutical ingredient. The placebo is also presented in a **film-coated tablet** form, ensuring blinding of the study participants and investigators. The placebo will be administered following the same schedule as the active treatment to maintain consistency across the study arms. Participant compliance with the placebo regimen will be similarly monitored to ensure the integrity of the trial results.

The efficacy of erectile rehabilitation with **Sildenafil** after proctectomy for rectal cancer will be assessed in this clinical trial through a series of primary and secondary endpoints. The primary endpoint is the patient response at 12 months post-operatively, defined by a score of at least 22 on the erectile function domain of the International Index of Erectile Function (IIEF), which includes six questions related to erection (Q1-Q5 and Q15). This score will determine if a patient is considered a responder.

Secondary endpoints include the IIEF erectile function domain score, which combines the six IIEF questions related to erection, measured at various timepoints: at surgery, D0, M3, M6, M9, and M12 postoperatively. Additionally, the International Index of Erectile Function global score, quality of life scores (EORTC QLQ-C30 and QLQ-CR29), LARS score, and Fecal Continence Score (Wexner score) will be measured at the same intervals. The trial will also evaluate the number of patients presenting spontaneous erections under treatment at M3, M6, M9, and without treatment at D0 and M12, as well as the number of patients with or without regular psychological follow-up. Compliance will be assessed by the number of unused tablets, with non-compliance defined as tablet intake of less than 80% over the 10-month treatment period. Adverse events (AEs) and serious adverse events (SAEs) will be recorded at D0, M3, M6, M9, and M12 postoperatively.