Randomized trial on Spinal Anaesthesia vs. General Anaesthesia (SAGA) on recovery after total hip, total knee, and unicompartmental knee arthroplasty

The primary objective of this study is to determine whether participants can safely and independently walk 5 meters, with or without a walking aid, within 6 hours post-surgery, contingent on the type of **anaesthesia** administered. This is clinically relevant as early mobilization is crucial for reducing postoperative complications and enhancing recovery in patients undergoing total hip, total knee, and unicompartmental knee arthroplasty due to **osteoarthritis** of the hip and knee.

Secondary objectives include evaluating:

• Postoperative pain, fulfilment of discharge criteria, vital signs, nausea and vomiting, dizziness, quality of recovery, postoperative delirium, urinary retention, and use of pain medication based on the anaesthesia type.
• Occurrence of emergency room contacts, complications, readmissions, and mortality within 30 days post-surgery.

The clinical trial focuses on individuals diagnosed with **osteoarthritis of the hip and knee**, aiming to assess their ability to walk 5 meters independently within 6 hours post-surgery, contingent on the type of anesthesia administered. The study population includes both male and female participants aged 18 years and older, who are cognitively intact and capable of providing informed consent. Participants must be able to speak and understand Danish. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. The selection criteria emphasize clinical and radiological evidence of knee osteoarthritis, suitable for primary total hip, total knee, or unicompartmental knee arthroplasty. Lifestyle factors such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the effects of spinal anesthesia versus general anesthesia on recovery outcomes following total hip, total knee, and unicompartmental knee arthroplasty in patients with **osteoarthritis of the hip and knee**. This study employs a **randomized**, **double-blind**, and controlled methodology to ensure the reliability and validity of the results. The trial is expected to span from November 2022 to May 2025, with participant involvement lasting up to 8 days, depending on the treatment regimen.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (≥18 years), language proficiency, and cognitive ability. Following the screening, eligible participants will be randomly assigned to receive either spinal or general anesthesia during their surgical procedure. The primary endpoint is the ability to safely and independently walk 5 meters within 6 hours post-surgery. Secondary endpoints include discharge criteria fulfillment, pain and opioid use, postoperative nausea and vomiting, dizziness, quality of recovery, and other postoperative complications.

Follow-up visits will be conducted to assess these endpoints, with the final visit marking the end of the study. Participants may be withdrawn from the study early if they experience adverse events, fail to comply with study procedures, or withdraw consent. The trial will utilize various medications, including **propofol**, **dexamethasone phosphate**, **bupivacaine hydrochloride**, and others, administered through appropriate routes such as intravenous, intrathecal, or oral, depending on the specific treatment protocol. The study aims to provide insights into the optimal anesthesia method for enhancing recovery in patients undergoing hip and knee arthroplasty.

The clinical trial involves the administration of several **experimental medications** and non-experimental treatments. **Propofol** is utilized in the form of an emulsion for injection/infusion. It is administered intravenously with a maximum daily and total dose of 3400 mg, over a treatment period of 1 day. **Dexamethasone phosphate** is provided as a solution for injection/infusion, also administered intravenously. The maximum daily and total dose is 100 mg, with a treatment period of 1 day. **Bupivacaine hydrochloride** is administered intrathecally in the form of an injection, with a maximum daily and total dose of 20 mg, over a 1-day treatment period.

**Tranexamic acid** is administered intravenously as a solution for infusion, with a maximum daily and total dose of 4 g, over a 1-day treatment period. **Paracetamol** is provided in tablet form for oral administration, with a maximum daily dose of 4 g and a total dose of 32 g, over an 8-day treatment period. **Sufentanil** is administered intravenously as a solution for injection, with a maximum daily and total dose of 5 µg/kg, over a 1-day treatment period. **Ondansetron** is also administered intravenously as a solution for injection, with a maximum daily and total dose of 8 mg, over a 1-day treatment period.

**Sodium lactate**, **sodium chloride**, **potassium chloride**, and **calcium chloride** are all administered as solutions for infusion, with a maximum daily and total dose of 10 liters for sodium lactate, sodium chloride, and calcium chloride, and 5 liters for potassium chloride, each over a 1-day treatment period. These are categorized as electrolyte solutions. **Remifentanil** is administered intravenously as a powder for concentrate for solution for injection/infusion, with a maximum daily and total dose of 20000 µg, over a 1-day treatment period.

**Celecoxib** is provided in capsule form for oral administration, with a maximum daily dose of 800 mg and a total dose of 6400 mg, over an 8-day treatment period. **Ropivacaine hydrochloride** is administered via local injection as a solution for injection, with a maximum daily and total dose of 200 ml, over a 1-day treatment period. Participant compliance with the dosing schedules is monitored throughout the trial to ensure adherence to the protocol.

The efficacy of the clinical trial titled "Randomized trial on Spinal Anaesthesia vs. General Anaesthesia (SAGA) on recovery after total hip, total knee, and unicompartmental knee arthroplasty" will be assessed using both primary and secondary endpoints. The primary endpoint is the ability of participants to safely and independently walk 5 meters within 6 hours of surgery, even when using a walking aid. This will be a direct measure of the immediate recovery and mobility post-surgery, depending on the type of anesthesia used.

Secondary endpoints include a range of parameters to evaluate broader aspects of recovery and potential complications. These include the fulfilment of discharge criteria, pain scores, opioid use, postoperative nausea and vomiting (PONV), dizziness scores, and the Quality of Recovery (QoR-15) scale. Additionally, the Opioid-Related Symptom Distress Scale (ORSDS) questionnaire and the 3-minute Diagnostic Interview – Confusion Assessment Method (3D-CAM) will be utilized to assess cognitive function and symptom distress. Other secondary endpoints include urinary retention, emergency room contacts, complications, readmission, or mortality within 30 days of surgery.