Evaluation of Bupivacaine Hydrochloride 10 mL vs. 20 mL for Popliteal Plexus Block on Opioid Consumption and Pain in Postoperative Total Knee Arthroplasty

The primary objective of this study is to evaluate the **analgesic effect** of Popliteal Plexus Block (PPB) using 10 mL versus 20 mL of local anesthetic, specifically **bupivacaine hydrochloride**, as an adjunct to Femoral Triangle Block in a multimodal analgesic regimen following primary unilateral total knee arthroplasty. The study hypothesizes that administering 20 mL of local anesthetic for PPB will result in a reduction of 24-hour postoperative **opioid consumption**. This is clinically relevant as it may enhance postoperative pain management and reduce reliance on opioids, which are associated with significant side effects and potential for dependency.

The clinical trial focuses on individuals experiencing **postoperative pain** following total knee arthroplasty. The study population includes both male and female participants aged over 18 years, with an **American Society of Anesthesiologists (ASA)** physical status classification of 1, 2, or 3, indicating a range from healthy individuals to those with mild systemic disease. Participants are required to be scheduled for primary total knee arthroplasty under spinal anesthesia and must be capable of providing written informed consent after fully understanding the study's contents. The trial does not involve a vulnerable population. 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 to evaluate the **analgesic** effect of Popliteal Plexus Block (PPB) using 10 mL versus 20 mL of local anesthetic, specifically **bupivacaine hydrochloride**, as an adjunct to Femoral Triangle Block in a multimodal analgesic regimen following primary unilateral total knee arthroplasty. This study is a randomized, controlled, and blinded trial, aiming to determine whether the increased volume of local anesthetic will result in decreased 24-hour postoperative opioid consumption. The trial is expected to commence recruitment on March 4, 2025, and conclude by February 1, 2027.

Participants will be involved in the study for a maximum treatment period of one day. The inclusion criteria require participants to be over 18 years of age, scheduled for primary total knee arthroplasty under spinal anesthesia, capable of providing informed consent, and classified as American Society of Anesthesiologists (ASA) physical status 1, 2, or 3. The primary endpoint is the total opioid consumption from the end of surgery until 24 hours postoperatively, expressed in oral morphine milligram equivalents (MME). Secondary endpoints include the frequency of patients with no opioid consumption, pain scores at rest and during a 10-meter walk with crutches, and patient-reported outcomes of recovery quality.

The sequence of study visits includes an initial screening visit to confirm eligibility based on the inclusion criteria. Follow-up visits will occur at specific time points: preoperatively, 6 hours post-surgery, and 24 hours post-surgery, to assess pain levels, opioid consumption, and functional recovery. The end-of-study visit will coincide with the 24-hour postoperative assessment. Participants may be terminated early from the study if they withdraw consent or if any adverse events occur that compromise their safety or the integrity of the study. The trial is categorized as low intervention, as the investigational product is routinely used for peripheral nerve block and is authorized for such use.

The clinical trial involves the use of **Bupivacaine Hydrochloride** as the experimental medication. **Bupivacaine** is a local anesthetic administered in the form of a solution for **perineural use**. The pharmaceutical form is identified by the code PHF00231MIG. The trial evaluates the effects of two different volumes of the anesthetic, specifically 10 mL and 20 mL, used in a Popliteal Plexus Block (PPB) as part of a multimodal analgesic regimen following primary unilateral total knee arthroplasty. The maximum daily dose of **Bupivacaine Hydrochloride** is 500 mg, with a maximum total dose of 150 mg per treatment period, which is limited to one day. The active substance is of chemical origin, and the product is not formulated for pediatric use.

In addition to the experimental treatment, the study incorporates a standard-of-care therapy, which includes a Femoral Triangle Block as part of the multimodal analgesic regimen. The trial is designed to assess the analgesic effect of the PPB with varying volumes of the local anesthetic, aiming to determine whether the use of 20 mL of **Bupivacaine Hydrochloride** can reduce 24-hour postoperative opioid consumption compared to 10 mL. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the protocol.

Efficacy in this clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoint is the total opioid consumption from the end of surgery (T0) until 24 hours postoperatively (T24), expressed in oral morphine milligram equivalents (MME). This measurement will provide a quantitative assessment of the analgesic effect of the Popliteal Plexus Block (PPB) with different volumes of local anesthetic.

Secondary endpoints include several parameters: the frequency of patients with no opioid consumption from T0 until T24, pain in the operated knee at rest and during a 10-meter walk with crutches, both scored by the Numeric Rating Scale (NRS) at specified timepoints (preoperative, 6 hours post-surgery (T6), and T24). Additionally, the frequency of patients unable to walk 10 meters with crutches at T6, and the frequency of Manual Muscle Test results less than Grade 3 in evaluations of dorsiflexion and plantarflexion of the ankle and knee extension at T6 will be recorded. Patient-reported outcomes will be measured using the Quality of Recovery 15 at T24.