Evaluation of Nocturnal Dexmedetomidine on Postoperative Sleep Quality and Fatigue in Elderly Patients Undergoing Major Thoracoscopic Lung Resection Surgery

The primary objective of this study is to evaluate the effect of the nocturnal administration of **dexmedetomidine** during the first night after surgery on postoperative sleep quality. This is clinically relevant as improved sleep quality may positively affect postoperative outcomes, such as reducing postoperative fatigue and muscle weakness, thereby enhancing recovery after surgery in elderly patients undergoing major procedures like thoracoscopic lung resection surgery.

Secondary objectives include the hypothesis that nocturnal administration of dexmedetomidine improves postoperative sleep quality and decreases the surgical endocrinological stress response. This may lead to improved postoperative outcomes, such as reduced postoperative fatigue and muscle weakness, and enhanced recovery. Additionally, it is hypothesized that by improving postoperative sleep and decreasing the stress response, cognitive function will be less affected, and markers of neuroinflammation will be diminished.

The clinical trial involves **patients aged 60 years or older** who are scheduled to undergo major surgery, specifically thoracoscopic lung resection surgery. The study population includes both male and female participants, and the trial does not focus on a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants were selected based on their age and the type of surgery they are scheduled to undergo. There are no specific lifestyle considerations such as diet or physical activity mentioned for this trial. The key inclusion criteria are adult patients aged 60 years or older who are scheduled for thoracoscopic lung resection surgery. The trial aims to evaluate the effect of nocturnal administration of dexmedetomidine on postoperative sleep quality, which may positively influence postoperative outcomes like fatigue and muscle weakness, thereby enhancing recovery after surgery.

The clinical trial is designed to evaluate the effect of nocturnal administration of **dexmedetomidine** on postoperative sleep quality and fatigue in patients aged 60 years or older undergoing major surgery, specifically thoracoscopic lung resection surgery. This is a **randomized**, **double-blind**, and **controlled** trial, with a primary objective to assess the quality of recovery on the first day following surgery using the Quality of Recovery Score (QoR-15). The trial is expected to commence on June 3, 2024, and conclude by March 31, 2026, with recruitment starting on April 1, 2024.

Participants will be involved in the study for a maximum treatment period of one day, receiving either the investigational product, Dexdor 100 micrograms/ml concentrate for solution for infusion, or a placebo, Sodium Chloride 0.9% Intravenous Infusion, both administered via **intravenous infusion**. The study will include several visits: an initial screening visit to confirm eligibility based on inclusion criteria such as age and scheduled surgery, followed by the administration of the study medication on the first postoperative night. Follow-up visits will assess various secondary endpoints, including postoperative muscle strength, cognitive function, and sleep quality, using validated tools like the Timed Up and Go test, CAMRY dynamometer, and Pittsburgh Sleep Quality Index.

The end-of-study visit will occur after the completion of all assessments, including the evaluation of inflammatory markers and melatonin production. Participants may be withdrawn from the study if they experience adverse reactions, fail to comply with study procedures, or withdraw consent. The trial aims to provide insights into the potential benefits of **dexmedetomidine** in enhancing postoperative recovery, with findings expected to contribute to improved clinical practices for elderly patients undergoing major surgery.

The clinical trial involves the administration of **Dexmedetomidine**, marketed under the name Dexdor 100 micrograms/ml concentrate for solution for infusion. This experimental medication is provided in the form of a concentrate for solution for infusion and is administered via **intravenous infusion**. The dosage is calculated based on the participant's body weight, with a maximum daily dose of 10 micrograms per kilogram. The treatment period is limited to a single day, and the administration is intended to occur during the first night following major surgery. The primary objective is to assess the impact of nocturnal dexmedetomidine on postoperative sleep quality and subsequent recovery outcomes in elderly patients.

In addition to the experimental treatment, the study utilizes **Sodium Chloride 0.9% Intravenous Infusion** as a comparator treatment. This non-experimental treatment is also administered via intravenous infusion and serves as a standard-of-care therapy. The maximum daily dose for sodium chloride is 100 milliliters, with the treatment period similarly restricted to one day. The sodium chloride solution is provided by Fresenius Kabi Limited and is used to maintain participant hydration and electrolyte balance during the trial. Compliance with the dosing schedule and administration is monitored to ensure adherence to the study protocol.

Efficacy in the clinical trial titled "The effect of nocturnal dexmedetomidine on postoperative sleep quality and fatigue after major surgery in elderly patients: DEXSLEEP study" will be assessed using a variety of parameters. The primary endpoint is the early quality of recovery on day 1 following surgery, compared to preoperative values, as measured by the Quality of Recovery Score (QoR-15). This score will be used to evaluate the early postoperative health status of the patient.

Secondary endpoints include assessments of postoperative muscle strength and physical ability using the Timed Up and Go test (TUG), and handgrip strength of the dominant hand measured by the CAMRY dynamometer. Fatigue will be evaluated using the Chalder fatigue questionnaire and the fatigue VAS scale. Health-related quality of life will be assessed with the EQ-5D questionnaire. Electroencephalographic (EEG) readings will be conducted in a subcohort of patients during the first postoperative night using a compact, wearable medical device.

Additional assessments include the Munich ChronoType Questionnaire (MCTQ) for evaluating sleep-wake cycles, the Pittsburgh Sleep Quality Index (PSQI) for subjective sleep quality, and the Consensus Sleep Diary for sleep evolution pre- and postoperatively. The Richards-Campbell Sleep Questionnaire (RCSQ) will evaluate the subjective quality of the first night after surgery. Postoperative delirium and cognitive impairment will be assessed using the 3-minute confusion assessment method (3D-CAM) and the Telephone Interview for Cognitive Status (TICS-40), respectively. Pain will be measured using NRS pain scores (0-10), and the occurrence of postoperative nausea and vomiting (PONV) will be recorded. Additionally, markers of the inflammatory surgical response and melatonin production will be monitored.