Randomized, Double-Blind, Placebo-Controlled Trial on Tapentadol Hydrochloride for Prevention of Chronic Postoperative Pain in Inguinal Hernia and Knee Surgery

The primary objective of this study is to **prevent the development of chronic postoperative pain** following inguinal hernia surgery and knee replacement surgery. This is clinically relevant as chronic postoperative pain can significantly impact a patient's quality of life and functional recovery. Understanding and preventing this condition can lead to improved postoperative outcomes and patient satisfaction.

Secondary objectives include:

• Evaluating the effect of **Tapentadol** compared to placebo on acute postoperative pain in patients undergoing elective inguinal hernia and knee replacement surgeries.
• Investigating the influence of pre-operative pain profiles, including inhibitory mechanisms measured by conditioned pain modulation (CPM) and facilitatory mechanisms indicated by central sensitization, on the development of chronic postoperative pain in patients with and without pre-existing chronic pain.
• Assessing the impact of Tapentadol and placebo on individual pain profiles, specifically inhibitory and facilitatory mechanisms, and their subsequent effect on the development of chronic postoperative pain.

The clinical trial focuses on individuals experiencing **chronic postoperative pain** following inguinal hernia surgery and knee replacement surgery. The study population includes both male and female participants, aged between 18 and 80 years, with an **American Society of Anesthesiologists** score of 1, 2, or 3, indicating a range from normal healthy patients to those with mild systemic disease. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants were selected based on specific inclusion criteria, ensuring a representative sample of the target demographic. Lifestyle factors such as diet, physical activity, and habits were not specified as part of the selection criteria.

The clinical trial is designed as a **randomized, double-blind, placebo-controlled** study aimed at evaluating the efficacy of **tapentadol hydrochloride** in preventing the development of **chronic postoperative pain** following inguinal hernia and knee replacement surgeries. The trial will span an estimated duration from May 2019 to January 2026. Participants will be randomly assigned to receive either the active treatment or a placebo, with neither the participants nor the investigators aware of the group assignments, ensuring the integrity of the blinding process.

The study will commence with an inclusion visit, where potential participants will be screened based on specific criteria, including an **American Society of Anesthesiologists score** of 1, 2, or 3, and an age range of 18 to 80 years. Following successful screening, eligible participants will be enrolled in the trial. The primary endpoint is to assess the effect of tapentadol compared to placebo on the development of chronic pain within the first year post-surgery.

Participants will be required to attend several follow-up visits throughout the study to monitor their progress and assess any adverse effects. These visits are crucial for collecting data on the primary endpoint and ensuring participant safety. The end-of-study visit will mark the conclusion of the participant's involvement, where final assessments will be conducted to gather comprehensive data on the treatment's efficacy and safety.

The expected length of participant involvement is up to four weeks, corresponding to the maximum treatment period with the study medication. 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 that compromise participant safety. The trial is conducted under strict regulatory standards to ensure the validity and reliability of the findings.

The clinical trial involves the administration of **PALEXIA Retard 50 mg** prolonged-release tablets, which contain the active substance **tapentadol hydrochloride**. This medication is designed to prevent the development of chronic postoperative pain following inguinal hernia and knee replacement surgeries. The pharmaceutical form of the medication is a prolonged-release tablet, ensuring a controlled release of the active ingredient over an extended period. The route of administration is oral, with a maximum daily dose of 200 mg and a total maximum dose of 5700 mg over the treatment period. The maximum treatment period is set at four weeks. The medication is not a pediatric formulation and is chemically derived. Compliance with the dosing schedule is monitored to ensure adherence to the treatment protocol.

In this randomized, double-blind, placebo-controlled trial, a placebo is used as the comparator treatment. The placebo is administered in the same pharmaceutical form and route as the experimental medication to maintain the study's blinding integrity. The placebo serves as a control to evaluate the efficacy of the experimental treatment in preventing chronic postoperative pain. Participants' adherence to the dosing schedule is closely monitored to ensure the reliability of the trial outcomes.

Efficacy in this clinical trial will be assessed by evaluating the primary endpoint, which is the effect of **Tapentadol** compared to placebo on the development of chronic pain in the first year after surgery. This assessment will focus on patients undergoing elective inguinal hernia surgery and knee replacement surgery. The trial is designed as a randomized, double-blind, placebo-controlled study to ensure the reliability and validity of the results. The primary endpoint will be measured and analyzed to determine the efficacy of Tapentadol in preventing chronic postoperative pain. The trial will follow a structured schedule for data collection and analysis, although specific timepoints and methods for these assessments are not detailed in the provided information.