Clinical trial NCT04399343: Dexmedetomidine for Prevention of Postoperative Delirium After Intracranial Operation for Brain Tumor
Official title: Dexmedetomidine for Prevention of Postoperative Delirium in Patients After Intracranial Operation for Brain Tumor: a Multicenter Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Central Nervous System Diseases
Keywords: dexmedetomidine
delirium
postoperative
intracranial operation
prevention
Lead sponsor: Capital Medical University
Sponsor class: OTHER
First posted: 2020-05-22
Enrollment: 700
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: Postoperative delirium is common after major surgery, and is associated with adverse outcomes. Systematic reviews and meta-analyses of randomized controlled trials have shown that perioperative administration of dexmedetomidine may decrease the incidence of postoperative delirium in patients after either cardiac or non-cardiac surgery. However, neurosurgical patients are often excluded in clinical trials of postoperative delirium.

In this prospective, multicenter, randomized, double-blinded, and placebo-controlled trial with two parallel arms, ICU admitted adult patients after intracranial operation for brain tumor will be enrolled. Low-dose dexmedetomidine will be applied during the early postoperative phase. The investigators aim to evaluate the efficacy and safety of low-dose dexmedetomidine for prevention of postoperative delirium in this patient population. The primary hypothesis is that, compared to the placebo group, the prophylactic use of low-dose dexmedetomidine can decrease the incidence of postoperative delirium without significant adverse events in patients after intracranial operation for brain tumor.

Detailed description: Postoperative delirium is common after major surgery, and is associated with adverse outcomes. However, patients with neurological illness are usually excluded from previous researches. Recently, limited studies have shown that the incidence of postoperative delirium in neurosurgical patients is approximately 20%, which is comparable to the results in other major surgery. Potential associations between postoperative delirium and adverse outcomes have also been found in neurosurgical patients. These results indicate that early prevention of postoperative delirium should be employed in this population.

As a highly selective α2-adrenergic receptor agonist, dexmedetomidine has been investigated as a preventive agent for postoperative delirium. Systematic reviews and meta-analyses of randomized controlled trials have shown that perioperative administration of dexmedetomidine may decrease the incidence of postoperative delirium in patients after either cardiac or non-cardiac surgery. However, neurosurgical patients are often excluded in clinical trials of postoperative delirium.

In this prospective, multicenter, randomized, double-blinded, and placebo-controlled trial with two parallel arms, ICU admitted adult patients after intracranial operation for brain tumor will be enrolled. Low-dose dexmedetomidine will be applied during the early postoperative phase. The investigators aim to evaluate the efficacy and safety of low-dose dexmedetomidine for prevention of postoperative delirium in this patient population. The primary hypothesis is that, compared to the placebo group, the prophylactic use of low-dose dexmedetomidine can decrease the incidence of postoperative delirium without significant adverse events in patients after intracranial operation for brain tumor.

Eligibility criteria: The inclusion criteria are adult patients after elective intracranial operation for brain tumor under general anesthesia and who are admitted to the ICU directly from the operating room or postoperative care unit.

The exclusion criteria include:

1. Admitted to the ICU after 22:00 PM;
2. Medical records documented preoperative history of mental or cognitive disorders including schizophrenia, epilepsy, Parkinsonism, or dementia;
3. Medical records documented inability to communicate in the preoperative period due to coma or language barrier;
4. History of drug abuse of psychoactive and anesthetic drugs;
5. Known preoperative severe sinus bradycardia (lower than 50 beats/min), sick sinus syndrome, second- or third-degree atrioventricular block, or left ventricular ejection fraction lower than 30%;
6. Serious hepatic dysfunction (Child-Pugh class C);
7. Severe renal dysfunction requiring renal replacement therapy before the surgery;
8. Allergies to ingredients or components of 5-\[(1S)-1-(2,3-dimethylphenyl)ethyl\]-1H-imidazole (dexmedetomidine hydrochloride);
9. American Society of Anesthesiologists (ASA) classification of IV to VI;
10. Moribund condition with low likelihood of survival for more than 24 hours;
11. Pregnancy or lactation women;
12. Current enrolment in another clinical trial;
13. Refuse to participate.

Primary outcomes:
measure: The incidence of postoperative delirium
timeFrame: From postoperative day 1 to day 5
Secondary outcomes:
measure: The incidence of adverse events
timeFrame: From the start of study agent infusion to postoperative day 1
measure: The incidence of non-delirium complications
timeFrame: From the start of study agent infusion to postoperative day 28
measure: Length of stay in the ICU
timeFrame: From the start of study agent infusion to postoperative day 28
measure: Length of stay in hospital
timeFrame: From the start of study agent infusion to postoperative day 28
measure: The incidence of all-caused deaths after the operation
timeFrame: From the start of study agent infusion to postoperative day 28
Other outcomes:
measure: The number of patients with the use of sedatives and analgesics
timeFrame: From the start of study agent infusion to postoperative day 1
measure: Pain intensity
timeFrame: From the start of study agent infusion to postoperative day 1
measure: Subjective sleep quality
timeFrame: From the start of study agent infusion to postoperative day 1
Locations:
city: Beijing
country: China
facility: Intensive Care Unit, Beijing Tiantan Hospital, Capital Medical University
state: Beijing
Study officials:
affiliation: Intensive Care Unit, Beijing Tiantan Hospital, Capital Medical University
name: Jian-Xin Zhou, MD
role: STUDY_CHAIR
References:
citation: He X, Cheng KM, Zhang L, Gu H, Qu X, Xu Y, Ma P, Zhou JX. Dexmedetomidine for the prevention of postoperative delirium in patients after intracranial operation for brain tumours (DEPOD study): a study protocol and statistical plan for a multicentre randomised controlled trial. BMJ Open. 2020 Nov 23;10(11):e040939. doi: 10.1136/bmjopen-2020-040939.