Dexmedetomidine-Esketamine Combination for Sedation and Analgesia in ICU Patients

NCT ID: NCT06468436

Last Updated: 2025-07-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

NA

Total Enrollment

1508 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-11-30

Study Completion Date

2030-12-01

Brief Summary

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Patients with mechanical ventilation in the intensive care unit (ICU) often develop anxiety and agitation, sleep distuebances, and delirium. Delirium occurrence is associated with worse early and long-term outcomes. Dexmedetomidine and ketamine are recommended for sedation and analgesia in ICU patients, but each may induce side effects. The sedative effects of dexmedetomidine can help mitigate the psychiatric side effects of esketamine. Recent studies showed that dexmedetomidine-esketamine combination improved analgesia and sleep quality without increasing psychiatric side effects. This trial is designed to test the hypothesis that dexmedetomidine-esketamine combination for sedation and analgesia in ICU patients with mechanical ventilation may reduce delirium and improve respiratory recovery.

Detailed Description

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Patients with respiratory failure or other severe conditions often require non-invasive or invasive mechanical ventilation in the Intensive Care Unit (ICU). The uncomfortable stimulation produced by mechanical ventilation may lead to anxiety and agitation of patients and adverse consequences such as ventilator asynchrony, increased oxygen consumption, stress responses, self-extubation, and potentially prolonged mechanical ventilation. The above factors, together with the ICU environment, underlying illnesses, treatment measures, and painful procedures, often result in sleep disturbances in ICU patients.

Mechanical ventilation, painful stimulation, and sleep disturbances are important risk factors of delirium in ICU patients. Delirium is an acutely occurred brain dysfunction symdrome characteristized with fluctuating disturbances in attention, cognition, and consciousness, and is reported to occur in up to 80% of ICU patients with mechanical ventilation. Delirium occurrence is associated with worse outcomes, including prolonged mechanical ventilation duration, extended ICU and hospital stays, increased healthcare burden and costs, and elevated mortality risk, as well as long-term sequelae including cognitive decline, reduced quality of life, and decreased survival.

Dexmedetomidine is a highly selective α2-adrenergic receptor agonist with sedative, analgesic, and anxiolytic effects. It exerts effects by activating the endogenous sleep-promoting pathways, inducing a state like non-rapid eye movement sleep. Ketamine is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist. Esketamine, the more potent enantiomer of ketamine, has a higher affinity for the NMDA receptor and is approximately twice as potent as ketamine, with a lower incidence of adverse effects. Both dexmedetomidine and ketamine are recommended for sedation and analgesia in ICU patients. However, sedative dose dexmedetomidine is associated with bradycardia and hypotension. Even low-dose esketamine can induce psychotropic side effects such as dissociation, hallucinations, and nightmares.

The sedative effects of dexmedetomidine can help mitigate the psychiatric side effects of esketamine. Recent studies showed that dexmedetomidine-esketamine combination improved analgesia and sleep quality without increasing psychiatric side effects. It is hypothesized that dexmedetomidine-esketamine combination for sedation and analgesia in ICU patients with mechanical ventilation may reduce delirium and improve respiratory recovery.

Conditions

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Aged Intensive Care Units Ventilators, Mechanical Dexmedetomidine Esketamine Delirium

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Dexmedetomidine-Esketamine Combination

Sedation-analgesia is provided with dexmedetomidine-esketamine combination for up to 14 days or until discharge from the ICU. The formulation consists of dexmedetomidine 200 μg/2 ml and esketamine 100 mg/4 ml, diluted with normal saline to a total volume of 50 ml, resulting in a dexmedetomidine concentration of 4 μg/ml and an esketamine concentration of 2 mg/ml.

Group Type EXPERIMENTAL

Dexmedetomidine-Esketamine Combination

Intervention Type DRUG

For patients with invasive ventilation, nighttime sedation (20:00-06:00) is provided with an initial infusion rate of \[0.05×kg\] ml/h which is increased by \[0.025×kg\] ml/h every 10 min, until the Richmond Agitation-Sedation Scale (RASS) reaches -2 to -1, maximal infusion rate reaches \[0.175×kg\] ml/h, or adverse reactions occur. Daytime sedation (06:00-20:00) is provided as above when considered necessary by the ICU physicians, with a target RASS score of -2 to +1.

For patients with non-invasive ventilation (including high-flow nasal oxygenation) or without assisted ventilation, nighttime sedation (20:00-06:00) is provided with an initial infusion rate of \[0.0125×kg\] ml/h which is increased by \[0.0125×kg\] ml/h every 10 min, until the RASS reaches -1, maximal infusion rate reaches \[0.05×kg\] ml/h, or adverse reactions occur. Daytime sedation (06:00-20:00) is typically not required but is provided when considered necessary by the ICU physicians, with a target RASS score of -1 to +1.

Dexmedetomidine

Sedation-analgesia is provided with dexmedetomidine for up to 14 days or until discharge from the ICU. The formulation consists of dexmedetomidine 200 μg/2 ml, diluted with normal saline to a total volume of 50 ml, resulting in a dexmedetomidine concentration of 4 μg/ml.

Group Type ACTIVE_COMPARATOR

Dexmedetomidine

Intervention Type DRUG

For patients with invasive ventilation, nighttime sedation (20:00-06:00) is provided with an initial infusion rate of \[0.05×kg\] ml/h which is increased by \[0.025×kg\] ml/h every 10 min, until the Richmond Agitation-Sedation Scale (RASS) reaches -2 to -1, maximal infusion rate reaches \[0.175×kg\] ml/h, or adverse reactions occur. Daytime sedation (06:00-20:00) is provided as above when considered necessary by the ICU physicians, with a target RASS score of -2 to +1.

For patients with non-invasive ventilation (including high-flow nasal oxygenation) or without assisted ventilation, nighttime sedation (20:00-06:00) is provided with an initial infusion rate of \[0.0125×kg\] ml/h which is increased by \[0.0125×kg\] ml/h every 10 min, until the RASS reaches -1, maximal infusion rate reaches \[0.05×kg\] ml/h, or adverse reactions occur. Daytime sedation (06:00-20:00) is typically not required but is provided when considered necessary by the ICU physicians, with a target RASS score of -1 to +1.

Interventions

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Dexmedetomidine-Esketamine Combination

For patients with invasive ventilation, nighttime sedation (20:00-06:00) is provided with an initial infusion rate of \[0.05×kg\] ml/h which is increased by \[0.025×kg\] ml/h every 10 min, until the Richmond Agitation-Sedation Scale (RASS) reaches -2 to -1, maximal infusion rate reaches \[0.175×kg\] ml/h, or adverse reactions occur. Daytime sedation (06:00-20:00) is provided as above when considered necessary by the ICU physicians, with a target RASS score of -2 to +1.

For patients with non-invasive ventilation (including high-flow nasal oxygenation) or without assisted ventilation, nighttime sedation (20:00-06:00) is provided with an initial infusion rate of \[0.0125×kg\] ml/h which is increased by \[0.0125×kg\] ml/h every 10 min, until the RASS reaches -1, maximal infusion rate reaches \[0.05×kg\] ml/h, or adverse reactions occur. Daytime sedation (06:00-20:00) is typically not required but is provided when considered necessary by the ICU physicians, with a target RASS score of -1 to +1.

Intervention Type DRUG

Dexmedetomidine

For patients with invasive ventilation, nighttime sedation (20:00-06:00) is provided with an initial infusion rate of \[0.05×kg\] ml/h which is increased by \[0.025×kg\] ml/h every 10 min, until the Richmond Agitation-Sedation Scale (RASS) reaches -2 to -1, maximal infusion rate reaches \[0.175×kg\] ml/h, or adverse reactions occur. Daytime sedation (06:00-20:00) is provided as above when considered necessary by the ICU physicians, with a target RASS score of -2 to +1.

For patients with non-invasive ventilation (including high-flow nasal oxygenation) or without assisted ventilation, nighttime sedation (20:00-06:00) is provided with an initial infusion rate of \[0.0125×kg\] ml/h which is increased by \[0.0125×kg\] ml/h every 10 min, until the RASS reaches -1, maximal infusion rate reaches \[0.05×kg\] ml/h, or adverse reactions occur. Daytime sedation (06:00-20:00) is typically not required but is provided when considered necessary by the ICU physicians, with a target RASS score of -1 to +1.

Intervention Type DRUG

Other Intervention Names

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Dexmedetomidine hydrochloride Esketamine hydrochloride Dexmedetomidine hydrochloride

Eligibility Criteria

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Inclusion Criteria

1. Aged ≥18 years;
2. Receiving invasive or non-invasive mechanical ventilation in the ICU, with an expected duration ≥24 hours;
3. Require sedation as judged by ICU physicians.

Exclusion Criteria

1. Pregnant or lactating women;
2. History of schizophrenia, epilepsy, Parkinson's disease, or myasthenia gravis;
3. Unable to communicate due to coma, severe dementia, or language barrier prior to invasive/non-invasive mechanical ventilation;
4. After stroke, hypoxic encephalopathy, traumatic brain injury, or neurosurgery;
5. Comorbid with hyperthyroidism or pheochromocytoma;
6. Left ventricular ejection fraction \<30%, sick sinus syndrome, severe sinus bradycardia (heart rate \<50 bpm), second-degree or higher atrioventricular block without a pacemaker, or systolic blood pressure \<90 mmHg despite use of vasopressors;
7. Severe liver dysfunction (Child-Pugh Class C), severe renal dysfunction (requiring dialysis), or expected survival ≤24 hours;
8. Allergy to dexmedetomidine and/or esketamine, or any other conditions that are considered unsuitable for study participation.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Peking University International Hospital

OTHER

Sponsor Role collaborator

Tianjin Medical University General Hospital

OTHER

Sponsor Role collaborator

Peking University First Hospital

OTHER

Sponsor Role lead

Responsible Party

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Dong-Xin Wang

Professor and Chairman, Department of Anesthesiology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Dong-Xin Wang, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Peking University First Hospital

Locations

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Peking University First Hospital

Beijing, Beijing Municipality, China

Site Status

Peking University International Hospital

Beijing, Beijing Municipality, China

Site Status

Tianjin Medical University General Hospital

Tianjin, Tianjin Municipality, China

Site Status

Countries

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China

Central Contacts

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Dong-Xin Wang, MD, PhD

Role: CONTACT

8610 83572784

Xian Su, MD, PhD

Role: CONTACT

8610 83575138

Facility Contacts

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Dong-Xin Wang, MD, PhD

Role: primary

8610 83572784

Xian Su, MD, PhD

Role: backup

8610 83575138

Gang Li, MD

Role: primary

+86 13521809822

Hong-Xun Yuan, MD

Role: backup

+86 13601199951

Ke-Liang Xie, MD

Role: primary

+86 15332112099

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Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2024-239

Identifier Type: -

Identifier Source: org_study_id

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