Low-Dose Dexmedetomidine for Delirium Prevention in Mechanically Ventilated Septic Patients

Sponsor

Peking University First Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT04876937

Collaborator

China-Japan Friendship Hospital (Other), Beijing Hospital (Other), Beijing Friendship Hospital (Other), Beijing Shijitan Hospital, Capital Medical University (Other), Beijing Tongren Hospital (Other)

116

Enrollment

Location

Arms

34.1

Anticipated Duration (Months)

3.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Delirium is common in septic patients, especially those receiving mechanical ventilation in the intensive care unit (ICU). Dexmedetomidine is a highly selective α2 adrenoreceptor agonist with anxiolytic, sedative, analgesic, and anti-inflammatory effects. Use of dexmedetomidine in mechanically ventilated ICU patients is associated with less delirium and improved outcomes. However, dexmedetomidine infusion produces dose-dependent bradycardia and hypotension; these limited the use of dexmedetomidine in ICU patients. This study is designed to test the hypothesis that low-dose dexmedetomidine infusion can also reduce delirium in mechanically ventilated ICU patients with sepsis.

Condition or Disease	Intervention/Treatment	Phase
Adult Intensive Care Unit Sepsis Mechanical Ventilation Delirium Dexmedetomidine	Drug: Dexmedetomidine Drug: Placebo (normal saline)	N/A

Detailed Description

Delirium is an acutely occurred and fluctuating disorder of consciousness, attention, and cognition. The occurrence of delirium is associated with worse outcomes including prolonged mechanical ventilation, prolonged length of stay in ICU and hospital, increased complications, higher in-hospital mortality, and evaluated medical expenses. It is also associated with worse long-term outcomes including cognitive decline, worse quality of life, and shortened long-term survival.

Dexmedetomidine is a highly selective α2 adrenoreceptor agonist with anxiolytic, sedative, analgesic, and anti-inflammatory effects. Studies showed that use of dexmedetomidine is associated with less delirium in ICU patients. Potential mechanisms may include better sleep quality, less consumption of opioids and benzodiazepines, and suppressed inflammatory response.

The incidence of sepsis in ICU patients is as high as 47.2%; 93% of septic patients relying on mechanical ventilation. Delirium is common in septic patients; the reported incidences varies from 20% to 50%. The incidence of delirium in critically ill patients with mechanical ventilation is up to 60-84%. However, the majority of mechanically ventilated ICU patients are sedated with propofol; only 10% of them are given dexmedetomidine. A main reason is that dexmedetomidine infusion is associated with dose-related bradycardia and hypotension.

In a previous study, might-time low-dose dexmedetomidine infusion (0.1 μg/kg/h) improved subjective sleep quality and reduced delirium in elderly patients admitted to ICU after surgery. In another study of ICU patients receiving mechanical ventilation, low-dose dexmedetomidine infusion (0-0.5 μg/kg/h) based on protocol sedation also reduced delirium and shortened mechanical ventilation without increasing adverse events. We hypothesized that, in ICU septic patients with mechanical ventilation, low-dose dexmedetomidine infusion (0.1-0.2 μg/kg/h) might also reduce delirium.

The purpose of this study is to investigate the effect of low-dose dexmedetomidine infusion on incidence of delirium in ICU septic patients with mechanical ventilation.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

116 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

Low-Dose Dexmedetomidine for Delirium Prevention in Mechanically Ventilated Septic Patients in Intensive Care Unit: a Multi-Center, Randomized, Double-Blind, Placebo-Controlled Trial

Actual Study Start Date :

May 28, 2021

Anticipated Primary Completion Date :

Mar 1, 2023

Anticipated Study Completion Date :

Apr 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dexmedetomidine group Dexmedetomidine is infused at a rate of 0.1-0.2 ug/kg/h during mechanical ventilation, for a maximum of 7 days.	Drug: Dexmedetomidine Dexmedetomidine is infused at a rate of 0.1-0.2 μg/kg/h (0.025-0.05 ml/kg/h) from study recruitment in the ICU during mechanical ventilation, for no more than 7 days. Other Names: Dexmedetomidine hydrochloride
Placebo Comparator: Placebo group Placebo (normal saline) is infused at a same rate as in the dexmedetomidine group during mechanical ventilation, for a maximum of 7 days.	Drug: Placebo (normal saline) Placebo (normal saline) is infused at a rate of 0.025-0.05 ml/kg/h from study recruitment in the ICU during mechanical ventilation, for no more than 7 days. Other Names: Normal saline

Arm

Intervention/Treatment

Experimental: Dexmedetomidine group

Dexmedetomidine is infused at a rate of 0.1-0.2 ug/kg/h during mechanical ventilation, for a maximum of 7 days.

Drug: Dexmedetomidine

Dexmedetomidine is infused at a rate of 0.1-0.2 μg/kg/h (0.025-0.05 ml/kg/h) from study recruitment in the ICU during mechanical ventilation, for no more than 7 days.

Other Names:

Dexmedetomidine hydrochloride

Placebo Comparator: Placebo group

Placebo (normal saline) is infused at a same rate as in the dexmedetomidine group during mechanical ventilation, for a maximum of 7 days.

Drug: Placebo (normal saline)

Placebo (normal saline) is infused at a rate of 0.025-0.05 ml/kg/h from study recruitment in the ICU during mechanical ventilation, for no more than 7 days.

Other Names:

Normal saline

Outcome Measures

Primary Outcome Measures

Incidence of delirium within the first 7 days after enrollment [Up to 7 days after enrollment]
Delirium is assessed twice daily (from 06:00 to 10:00 and from 18:00 to 20:00) with the Confusion Assessment Method for the intensive care unit (CAM-ICU).

Secondary Outcome Measures

Duration of mechanical ventilation. [Up to 30 days after enrollment]
Duration of mechanical ventilation after study enrollment.
Length of stay in the ICU. [Up to 30 days after enrollment]
Length of stay in the ICU after study enrollment.
Length of stay in the hospital. [Up to 30 days after enrollment]
Length of stay in the hospital after study enrollment.
Incidence of non-delirium complications. [Up to 30 days after enrollment]
Non-delirium complications are defined as newly occurred medical conditions other than delirium that required therapeutic intervention, i.e., grade 2 or higher on Clavien-Dindo classification.
All-cause 30-day mortality [Up to 30 days after enrollment]
All-cause 30-day mortality after study enrollment.
30-day cognitive function [On the 30th day after enrollment.]
Cognitive function is assessed with the Modified Telephone Interview for Cognitive Status (TICS-m) which is a 12-item questionnaire that verbally assesses global cognitive function via telephone. The score ranges from 0 to 50, with higher score indicating better function.
30-day quality of life [On the 30th day after enrollment.]
Quality-of-life is assessed with the World Health Organization Quality of Life brief version (WHOQOL-BREF) which is 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.

Other Outcome Measures

Pain intensity. [Up to 7 days after enrollment.]
Assessed twice daily (from 06:00 to 10:00 and from 18:00 to 20:00) with the Numeric Rating Scale (NRS, an 11-point scale where 0 indicated no pain and 10 indicated the worst possible pain).
Subjective sleep quality. [Up to 7 days after enrollment.]
Assessment once daily (from 06:00 to 10:00) with the Numeric Rating Scale (NRS, an 11-point scale where 0 indicated the best possible sleep and 10 indicated the worst possible sleep).
Score of Acute Physiology and Chronic Health Evaluation II (APACHE II). [Within 24 hours after enrollment.]
Score of Acute Physiology and Chronic Health Evaluation II (APACHE II).
6-month cognitive function. [At the end of 6 months after enrollment.]
Cognitive function is assessed with the Modified Telephone Interview for Cognitive Status (TICS-m) which is a 12-item questionnaire that verbally assesses global cognitive function via telephone. The score ranges from 0 to 50, with higher score indicating better function.
6-month quality of life. [At the end of 6 months after enrollment.]
Quality-of-life is assessed with the World Health Organization Quality of Life brief version (WHOQOL-BREF) which is 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.
Overall survival [Up to 1 year after enrollment.]
Overall survival
1-year cognitive function. [At the end of 1 year after enrollment.]
Cognitive function is assessed with the Modified Telephone Interview for Cognitive Status (TICS-m) which is a 12-item questionnaire that verbally assesses global cognitive function via telephone. The score ranges from 0 to 50, with higher score indicating better function.
1-year quality of life. [At the end of 1 year after enrollment.]
Quality-of-life is assessed with the World Health Organization Quality of Life brief version (WHOQOL-BREF) which is 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Aged 18 years or older;
Admitted to the ICU;
With expected mechanical ventilation duration ≥12 hours;
Meet the diagnostic criteria of sepsis (sepsis 3.0; patient with infection and a sequential organ failure assessment score ≥2).

Exclusion Criteria:

Refuse to participate in;
Pregnancy;
History of schizophrenia, epilepsy, parkinsonism, or myasthenia gravis;
Inability to communicate (coma, profound dementia, or language barrier);
Brain injury or neurosurgery;
Left ventricular ejection fraction (LVEF) less than 30%, sick sinus syndrome, severe sinus bradycardia (<50 beats per min [bpm]), or second degree or greater atrioventricular block without pacemaker;
Serious hepatic dysfunction (Child-Pugh class C);
Serious renal dysfunction (undergoing dialysis);
With expected survival for no more than 24 hours;
Allergic to dexmedetomidine;
Other conditions that were considered unsuitable for study participation.