Comparative Efficacy of Pectoral Nerve Block with Liposomal Bupivacaine versus Levobupivacaine in Post-Mastectomy Pain Management

The primary objective of this study is to evaluate whether postoperative **NRS pain scores** in the breast are lower in patients undergoing mastectomy who receive a preoperative Pectoral Nerve (PECS II) block with liposomal bupivacaine compared to those who receive the block with levobupivacaine. This is clinically relevant as it aims to improve postoperative pain management, potentially enhancing recovery and patient comfort following breast cancer surgery.

Secondary objectives include:

• Assessing whether perioperative opioid use is reduced in patients receiving liposomal bupivacaine compared to levobupivacaine.
• Evaluating postoperative NRS pain scores in the axilla.
• Determining the need for additional painkillers postoperatively.
• Investigating the incidence of chronic pain (> 12 weeks) post-mastectomy.
• Measuring patient satisfaction using the BREAST-Q BCT.
• Assessing the duration of postoperative observation in the recovery room.
• Evaluating the time until hospital discharge.
• Examining the occurrence of postoperative nausea and vomiting (PONV).

The clinical trial focuses on **postoperative and chronic pain** after breast cancer surgery, specifically assessing pain management following mastectomy. The study population comprises female participants only, with an age range corresponding to categories 3 and 4, which typically includes adults and older adults. Participants are generally in good health, classified as ASA Class I-III, indicating they are either healthy or have mild to severe systemic disease. The trial does not include vulnerable populations. The selection criteria require participants to have undergone unilateral mastectomy and to provide written informed consent in accordance with ICH/GCP and national regulations. The sponsor has not provided information regarding the total number of participants. Lifestyle factors such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed as a **randomized**, **controlled**, and **double-blind** study to evaluate the efficacy of a Pectoral Nerve (PECS II) Block using long-acting liposomal **bupivacaine** compared to **levobupivacaine** for managing postoperative and chronic pain following mastectomy surgery. The trial aims to determine if postoperative Numeric Rating Scale (NRS) pain scores in the breast are lower in patients receiving a preoperative PECS II block with liposomal bupivacaine than those receiving levobupivacaine. The study is set to commence recruitment on October 19, 2023, and is expected to conclude by October 19, 2025.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as undergoing unilateral mastectomy, providing written informed consent according to ICH/GCP and national regulations, and being classified as ASA Class I-III. Following the screening, participants will be randomly assigned to receive either the test or comparator drug. The trial will include follow-up visits to monitor primary and secondary endpoints, such as postoperative NRS pain scores in the breast and axilla, intraoperative and postoperative need for opiates, patient-reported chronic pain, patient satisfaction, and any complications.

The expected duration of participant involvement is approximately one day, corresponding to the maximum treatment period. However, participants may be withdrawn from the study early if they experience significant adverse events, fail to comply with the study protocol, or withdraw consent. The end-of-study visit will assess the final outcomes and ensure the safety and well-being of the participants. The trial's primary endpoint is the postoperative NRS pain score in the breast, while secondary endpoints include various measures of pain management, patient satisfaction, and safety outcomes.

The clinical trial involves the administration of **EXPAREL** liposomal, a **prolonged-release dispersion for injection** containing the active substance **bupivacaine**. This experimental medication is provided in a concentration of 133 mg/10 mL and is administered via injection. The maximum daily and total dose is 266 mg, with a treatment period limited to one day. The formulation is designed to release the active substance over an extended period, providing prolonged analgesic effects. The product is manufactured by PACIRA IRELAND LIMITED and is not a pediatric formulation.

The comparator treatment in the study is **Levobupivacaïne Fresenius Kabi**, a **solution for injection/infusion** containing the active substance **levobupivacaine**. This medication is administered at a concentration of 5 mg/mL, with a maximum daily and total dose of 175 mg. The administration route is injection, and the treatment period is also limited to one day. This product is manufactured by FRESENIUS KABI NEDERLAND B.V. and is used to compare the efficacy of the experimental medication.

Additionally, the study includes the use of **Bupivacaïne Eugia**, a **solution for injection** containing **bupivacaine hydrochloride, anhydrous**. This medication is administered at a concentration of 5 mg/mL, with a maximum daily and total dose of 150 mg. The administration is via injection, and the treatment period is restricted to one day. This product is manufactured by EUGIA PHARMA (MALTA) LTD and serves as another comparator in the trial.

The efficacy of the clinical trial titled "APECS II: Comparing the efficacy of Pectoral Nerve (PECS II) Block with long-acting liposomal bupivacaine versus levobupivacaine for Mastectomy Surgery" will be assessed using several parameters. The primary endpoint for evaluating efficacy is the postoperative **NRS pain scores** in the breast. Secondary endpoints include postoperative NRS pain scores in the axilla, intraoperative and postoperative need for opiates or other painkillers, patient-reported chronic pain lasting more than 12 weeks, patient satisfaction measured by the BREAST-Q BCT, postoperative observation time in the recovery room, time until hospital discharge, use of additional anti-emetics for PONV, incidence of vomiting, and complications such as wound infection rate, hematoma, abscess, pneumothorax, and local anesthesia systemic toxicity.

The trial aims to determine if postoperative NRS pain scores in the breast are lower in patients receiving a preoperative PECS II block with liposomal bupivacaine compared to those receiving levobupivacaine. The efficacy parameters will be collected and analyzed at specified timepoints, although the exact schedule is not detailed in the provided data. The trial is a multicenter prospective randomized controlled trial, and the estimated recruitment start date is October 19, 2023, with an estimated end date of October 19, 2025.