Clinical trial NCT04876937: Low-Dose Dexmedetomidine for Delirium Prevention in Mechanically Ventilated Septic Patients
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Adult
Intensive Care Unit
Sepsis
Mechanical Ventilation
Delirium
Dexmedetomidine
Keywords: Adult
Intensive care unit
Sepsis
Mechanical ventilation
Delirium
Dexmedetomidine
Lead sponsor: Peking University First Hospital
Sponsor class: OTHER
Collaborators: name: China-Japan Friendship Hospital
name: Beijing Hospital
name: Beijing Friendship Hospital
name: Beijing Shijitan Hospital, Capital Medical University
name: Beijing Tongren Hospital
First posted: 2021-05-07
Enrollment: 116
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

1. Refuse to participate in;
2. Pregnancy;
3. History of schizophrenia, epilepsy, parkinsonism, or myasthenia gravis;
4. Inability to communicate (coma, profound dementia, or language barrier);
5. Brain injury or neurosurgery;
6. 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;
7. Serious hepatic dysfunction (Child-Pugh class C);
8. Serious renal dysfunction (undergoing dialysis);
9. With expected survival for no more than 24 hours;
10. Allergic to dexmedetomidine;
11. Other conditions that were considered unsuitable for study participation.

Primary outcomes:
measure: Incidence of delirium within the first 7 days after enrollment
timeFrame: Up to 7 days after enrollment
Secondary outcomes:
measure: Duration of mechanical ventilation.
timeFrame: Up to 30 days after enrollment
measure: Length of stay in the ICU.
timeFrame: Up to 30 days after enrollment
measure: Length of stay in the hospital.
timeFrame: Up to 30 days after enrollment
measure: Incidence of non-delirium complications.
timeFrame: Up to 30 days after enrollment
measure: All-cause 30-day mortality
timeFrame: Up to 30 days after enrollment
measure: 30-day cognitive function
timeFrame: On the 30th day after enrollment.
measure: 30-day quality of life
timeFrame: On the 30th day after enrollment.
Other outcomes:
measure: Pain intensity.
timeFrame: Up to 7 days after enrollment.
measure: Subjective sleep quality.
timeFrame: Up to 7 days after enrollment.
measure: Score of Acute Physiology and Chronic Health Evaluation II (APACHE II).
timeFrame: Within 24 hours after enrollment.
measure: 6-month cognitive function.
timeFrame: At the end of 6 months after enrollment.
measure: 6-month quality of life.
timeFrame: At the end of 6 months after enrollment.
measure: Overall survival
timeFrame: Up to 1 year after enrollment.
measure: 1-year cognitive function.
timeFrame: At the end of 1 year after enrollment.
measure: 1-year quality of life.
timeFrame: At the end of 1 year after enrollment.
Locations:
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
Study officials:
affiliation: Peking University First Hospital
name: Dong-Xin Wang, MD,PhD
role: PRINCIPAL_INVESTIGATOR
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