MInimizing Delirium With Nasal Dexmedetomidine-InducEd Sleep (MIDDIES) (MIDDIES)

Minimizing Delirium With Nasal Dexmedetomidine-Induced Sleep in Older Patients Undergoing Major Abdominal Surgery: : a Randomized, Double-blind, Placebo-controlled Trial

This study aims to determine whether, compared with placebo, the nighttime self-administration of a nasal dexmedetomidine is effective at inducing sleep and preventing postoperative delirium in high-risk patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Postoperative Delirium (POD); Major Abdominal Surgery; Sleep Disturbances; Intranasal Dexmedetomidine
• Intervention / Treatment: Drug: Dexmedetomidine; Drug: Placebo

Detailed Description

Delirium is an acute, short-term brain dysfunction characterized by fluctuating consciousness, cognitive decline, inattention, and sleep-wake cycle disruption. Postoperative delirium (POD), occurring predominantly within the first postoperative week (especially days 3-5 in elderly patients), affects 11-45% of older adults after major surgery. POD prolongs hospitalization, increases morbidity and mortality 5,65,6, yet its pathophysiology remains unclear, and evidence-based pharmacological prevention is lacking. Thus, effective POD prevention strategies are urgently needed.

Preoperative anxiety, a modifiable risk factor for POD, affects 11-80% of surgical patients. It contributes to sleep disturbances (e.g., insomnia, early awakening), which may exacerbate POD via neuroendocrine and immune dysregulation. However, benzodiazepines (e.g., lorazepam, diazepam, midazolam), though effective anxiolytics, increase delirium risk and are contraindicated preoperatively per current guidelines.

Dexmedetomidine (DEX), a selective α2-adrenoceptor agonist, induces physiological non-REM sleep without respiratory depression or hemodynamic instability. Its nasal formulation offers high bioavailability (82%), ease of administration, and is approved in China for preoperative sedation/anxiety. While intravenous (IV) DEX reduces POD in predominant ICU settings, its use in general wards remains unexplored. Preclinical studies suggest DEX enhances glymphatic clearance and exerts anti-inflammatory effects, potentially mitigating the development of POD. This study thus hypothesize that a nasal dexmedetomidine is effective at inducing sleep and preventing postoperative delirium in high-risk patient population. We set to demonstrate that to determine whether, compared with placebo, the nighttime self-administration of a nasal dexmedetomidine is effective at inducing sleep and preventing postoperative delirium in older patients undergoing major abdominal surgery.

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Mentying Ding, MD.; Phone Number: +86-15170375679; Email: 15170375679@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Aged 65-90 years
• Scheduled for a major abdominal surgery with estimated surgery time ≥ 2 hours

Exclusion Criteria:

• Blind, deafness or the inability to speak mandarin
• Allergy to dexmedetomidine.
• Renal and liver failure requiring dialysis or Child-Pugh score > 5
• Follow-up difficulties (i.e. active substance abuse, psychotic disorder, homelessness)
• Previous major abdominal or cardiac surgery within 1 year of surgical procedure
• Chronic therapy with benzodiazepines and/or antipsychotics. Severe deficit due to structural or anoxic brain damage
• Body weight < 35 kg

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Intranasal water for injection (4 sprays, identical volume as nasal dexmedetomidine; Hengrui Medicine, China) self-administered preoperatively (~9 PM) and optionally on the night of surgery (patient decides dose: 0, 2 sprays, or 4 sprays).
Experimental: Dexmedetomidine	Drug: Dexmedetomidine; Intranasal dexmedetomidine (100 µg total: 4 sprays, 25 µg/spray; Hengrui Medicine, China) self-administered preoperatively (~9 PM) and optionally on the night of surgery (patient decides dose: 0, 2 sprays, or 4 sprays).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of postoperative delirium	Confusion Assessment Method	Up to postoperative day (POD) 7 or discharge (whichever first).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Delirium severity	Confusion Assessment Method Score	Up to postoperative day (POD) 7 or discharge (whichever first)
Physical activity	Fitbit Flex2 tracker	Up to postoperative day (POD) 3
Sleep quality	Fitbit Flex2 tracker and Athens Insomnia Scale	Up to postoperative day (POD) 3
Anxiety	Hamilton Anxiety Scale	Up to postoperative day (POD) 3
Pain intensity	Numerical Rating Scale	Up to postoperative day (POD) 3
Opioid consumption	Intravenous morphine equivalents	Up to postoperative day (POD) 3
Health related quality of life	Health related quality of life assessed with the SF-36 health survey	On postoperative day (POD) 3 and 30
Quality of Recovery	The Quality of Recovery-15 questionnaire	Up to postoperative day (POD) 3
Postoperative Nausea and Vomiting	Postoperative Nausea and Vomiting Scale	Up to postoperative day (POD) 3
Post-anesthesia Care Unit (PACU) length of stay	Post-anesthesia Care Unit (PACU) length of stay	Up to postoperative day (POD) 1

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Optional intranasal administration on the night of surgery	Optional intranasal administration of the same spray (patient decides dose: 0, 2 sprays, or 4 sprays)	At night of the surgery
Length of Hospital Stay	Medical Record Review	From postoperative day 0 until date of hospital discharge (Up to 30 days)
Cognitive function	Abbreviated Mental Test Score	Up to postoperative day (POD) 30

Collaborators and Investigators

• Sponsor: Sixth Affiliated Hospital, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: May 30, 2025
• First Submitted That Met QC Criteria: April 12, 2026
• First Posted (Actual): April 20, 2026

Study Record Updates

• Last Update Posted (Actual): April 20, 2026
• Last Update Submitted That Met QC Criteria: April 12, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: intranasal administration; dexmedetomidine
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Postoperative Complications; Pathologic Processes; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Sleep Wake Disorders; Delirium; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Emergence Delirium; Parasomnias; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Imidazoles; Dexmedetomidine
• Other Study ID Numbers: 2025ZSLYEC-227

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified data and a data dictionary will be made available upon reasonable request to researchers who provide a methodologically sound proposal and whose use of the data has been approved the study authors. Data will be made available immediately following publication, with no anticipated end date, to achieve the aims specified in the approved proposal. Proposals should be directed to ruanxc@mail.sysu.edu.cn.
• IPD Sharing Time Frame: Immediately
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No