Efficacy of Perioperative Duloxetine in Reducing Chronic Postsurgical Pain Incidence in High-Risk Patients Post-Inguinal Hernia Repair: A Randomized Controlled Trial

The primary objective of this study is to determine the **efficacy** of duloxetine versus placebo in reducing the incidence of chronic postsurgical pain (CPSP) at 4 months in patients at high risk of this complication following inguinal hernia repair. This is clinically relevant as CPSP is a significant postoperative complication that can adversely affect patient recovery and quality of life.

Secondary objectives include:

• Comparing the characteristics, intensity, and impact of CPSP on quality of life between the intervention and control groups.
• Assessing safety by comparing the rates of adverse effects of perioperative duloxetine and placebo for the primary prevention of CPSP.

The clinical trial focuses on evaluating the efficacy of duloxetine in reducing the incidence of **chronic postsurgical pain** after inguinal hernia repair. The study population includes both male and female participants, with an age range that encompasses adults and older adults. Participants are required to reside in Spain for the duration of the trial and are scheduled for open inguinal hernia repair, either as inpatient or outpatient procedures. The trial specifically targets individuals at high risk of post-surgical pain chronification, with a risk of 16% or greater as determined by the GENDOLCAT risk scale. The sponsor has not provided information regarding the total number of participants. The trial does not include vulnerable populations, and no specific lifestyle considerations such as diet or physical activity are highlighted in the selection criteria.

The clinical trial is designed to evaluate the **efficacy** of **duloxetine** in reducing the incidence of chronic postsurgical pain (CPSP) following inguinal hernia repair. This is a multicenter, randomized, double-blind, controlled trial. Participants will be randomly assigned to receive either **duloxetine** or a placebo, with the intervention being administered in the form of gastro-resistant capsules. The trial is expected to span from October 2023 to October 2027, with participant involvement lasting up to 21 days, corresponding to the maximum treatment period.

The study will commence with an inclusion (screening) visit, where eligibility will be assessed based on criteria such as being male, residing in Spain for the trial duration, and having a risk of post-surgical pain chronification of 16% or higher, as determined by the GENDOLCAT risk scale. Following successful screening, participants will be enrolled and randomized. The primary endpoint is the incidence of CPSP at four months post-surgery, while secondary endpoints include quality of life assessed via the SF-12 questionnaire and the rate of adverse events perioperatively.

Participants will attend follow-up visits to monitor their response to the treatment and any adverse effects. The end-of-study visit will conclude the trial for each participant, where final assessments will be conducted. Conditions that may lead to early termination from the study include non-compliance with the study protocol, withdrawal of consent, or the occurrence of significant adverse events. The trial aims to provide valuable insights into the potential benefits of **duloxetine** in managing CPSP, contributing to improved postoperative care for patients undergoing inguinal hernia repair.

The clinical trial involves the administration of **Duloxetine**, marketed under the name Dulotex 30 mg cápsulas duras gastrorresistentes EFG. This medication is provided in the form of **gastro-resistant capsules, hard**, and is intended for oral administration. Each capsule contains 30 mg of the active substance **duloxetine**, a chemical compound. The maximum daily dose is 30 mg, with a total treatment period not exceeding 21 days. The capsules have been repacked for blinding purposes to maintain the integrity of the study. The pharmaceutical product is authorized in Spain and manufactured by Neuraxpharm Spain, S.L.U. Compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol.

The comparator treatment in this study is a placebo, consisting of capsules of **maltodextrine**. These capsules are designed to mimic the appearance and administration route of the active treatment, ensuring the blinding of participants and investigators. The placebo is administered orally, following the same dosing schedule as the active treatment, with a maximum treatment period of 21 days. The use of a placebo is critical in evaluating the efficacy of duloxetine in reducing the incidence of chronic postsurgical pain after inguinal hernia repair. Participant compliance with the placebo regimen is also monitored to maintain the study's validity.

The efficacy of **duloxetine** in reducing the incidence of chronic post-surgical pain (CPSP) will be assessed in a multicenter randomized controlled trial involving patients undergoing inguinal hernia repair. The primary endpoint for evaluating efficacy is the incidence of CPSP at 4 months post-surgery. This will be measured to determine the effectiveness of duloxetine compared to a placebo in patients identified as high risk for developing CPSP.

Secondary endpoints include the assessment of quality of life using the SF-12 questionnaire and the rate of adverse events occurring perioperatively. These parameters will provide additional insights into the impact of duloxetine on patient outcomes beyond pain reduction. The trial will involve the administration of duloxetine in a gastro-resistant capsule form, with a maximum daily dose of 30 mg, over a treatment period of up to 21 days. The study is designed to ensure rigorous data collection and analysis to support the evaluation of duloxetine's efficacy in this patient population.