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Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT06468436
Other study ID # 2024-239
Secondary ID
Status Not yet recruiting
Phase N/A
First received
Last updated
Start date July 2024
Est. completion date December 2030

Study information

Verified date June 2024
Source Peking University First Hospital
Contact Dong-Xin Wang, MD, PhD
Phone 8610 83572784
Email wangdongxin@hotmail.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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.


Description:

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.


Recruitment information / eligibility

Status Not yet recruiting
Enrollment 1508
Est. completion date December 2030
Est. primary completion date June 2030
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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.

Study Design


Intervention

Drug:
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.
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.

Locations

Country Name City State
China Peking University First Hospital Beijing Beijing
China Peking University International Hospital Beijing Beijing
China Tianjin Medical University General Hospital Tianjin Tianjin

Sponsors (3)

Lead Sponsor Collaborator
Peking University First Hospital Peking University International Hospital, Tianjin Medical University General Hospital

Country where clinical trial is conducted

China, 

References & Publications (70)

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Outcome

Type Measure Description Time frame Safety issue
Other Proportion of patients without delirium within 14 days Delirium is assessed twice daily with the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) or the 3-Minute Diagnostic Assessment for Delirium using the Confusion Assessment Method (3D-CAM) during the 14-day period after enrollment or until hospital discharge. Up to 14 days after enrollment
Other Proportion of patients without delirium or coma within 14 days Delirium is assessed twice daily with the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) or the 3-Minute Diagnostic Assessment for Delirium using the Confusion Assessment Method (3D-CAM). Coma is defined as Richmond Agitation Sedation Scale (score ranges from -5 [unarousable] to +4 [combative] and 0 indicates alert and calms) of -4 or -5. Up to 14 days after enrollment
Other Length of stay in hospital after enrollment Length of stay in hospital after enrollment. Up to 30 days after enrollment
Other Incidence of major complications within 30 days Major complications are defined as new-onset medical conditions other than delirium that are deemed harmful and require therapeutic intervention, that is grade II or higher on the Clavien-Dindo classification. Up to 30 days after enrollment
Other Cognitive function at 30 days Cognitive function is assessed with the Montreal Cognitive Assessment-telephone version (T-MoCA; score ranges from 0 to 22, with higher score indicating better cognitive function). At 30 days after enrollment
Other Quality of life at 30 days Quality of life is assessed with the World Health Organization Quality of Life brief version (WHOQOL-BREF), a 24-item questionnaire that assesses the quality of life in physical, psychological, and social relationship, and environmental domains. The score ranges from 0 to 100 for each domain, with higher score indicating better function. At 30 days after enrollment
Primary Incidence of delirium within 14 days Delirium is assessed twice daily with the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) or the 3-Minute Diagnostic Assessment for Delirium using the Confusion Assessment Method (3D-CAM) during the 14-day period after enrollment or until hospital discharge. Positive result of delirium assessments at any timepoint is defined as occurrence of delirium. Up to 14 days after enrollment
Secondary Days alive without delirium or come during the 14-day period Delirium is assessed twice daily with the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) or the 3-Minute Diagnostic Assessment for Delirium using the Confusion Assessment Method (3D-CAM). Coma is defined as Richmond Agitation Sedation Scale (score ranges from -5 [unarousable] to +4 [combative] and 0 indicates alert and calms) of -4 or -5. Positive results at any timepoint is defined as occurrence of delirium or coma. Up to 14 days after enrollment
Secondary Ventilator-free days within 30 days Mechanical ventilation includes both invasive and non-invasive ventilation, but do not include high-flow nasal oxygenation. Up to 30 days after enrollment
Secondary Length of stay in the ICU Length of stay in the ICU. Up to 30 days after enrollment
Secondary 30-day all-cause mortality 30-day all-cause mortality. Up to 30 days after enrollment
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