Dexmedetomidine After Cardiac Surgery for Prevention of Delirium (EXACTUM)

Regional University Hospital Center (CHRU)

Status and phase: Completed; Phase 3

Conditions: ICU Delirium

Treatments: Drug: Sodium chloride 0.9%; Drug: Dexmedetomidine

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03477344

29BRC18.0051 (EXACTUM)

Details and patient eligibility

About

We designed a prospective, double blind, randomized, controlled versus placebo study to evaluate the efficacy of nightly low dose of Dexmedetomidine infusion to promote sleep and lower delirium in a population of post cardiac surgery patients. This population is characterized by longer ICU stay, more physical restraints such as catheters and drains, pain and sleep deprivation. It is associated with higher prevalence of Delirium and agitation leading to exposure to severe agitation related adverse events.

Full description

Delirium occurs in about 25% of patients after cardiac surgery. It is an independent factor of poor outcome and recovery after ICU stay as it is associated with mortality and impaired mental function one year after its onset. It is associated with increased public health costs during the hospital stay and after.

The use of Dexmedetomidine as sedative medication is more and more described. It is well established that it can lower delirium onset comparatively to Midazolam or Propofol. It is also useful in agitated delirium as a complementary medication to reduce delirium duration. A study published by Su et al in 2016 assessed the efficacy of Dexmedetomidine in prevention of post-surgical delirium for patients older than 65 years after non cardiac surgery. Patients were mainly admitted in the ICU after abdominal surgery for malignant tumor. Dexmedetomidine was used at very low dose to promote sleep during ICU stay. In this study the onset of delirium was significantly lowered by one half for the first week after surgery. However, this study only focused on older patients and non-cardiac surgery population with short mechanical ventilation duration, short ICU stay and low incidence of complications.

We designed a prospective, double blind, randomized, controlled versus placebo study to evaluate the efficacy of nightly low dose of Dexmedetomidine infusion to promote sleep and lower delirium in a population of post cardiac surgery patients. This population is characterized by longer ICU stay, more physical restraints such as catheters and drains, pain and sleep deprivation. It is associated with higher prevalence of Delirium and agitation leading to exposure to severe agitation related adverse events. In the study by Su and al low dose Dexmedetomidine did not induce adverse events such as bradycardia or hypotension, conversely safety outcomes showed that Dexmedetomidine use was associated with fewer tachycardia and hypoxaemia. Moreover, data shows that Dexmedetomidine is likely to play a cardio protective role in the same way as Clonidine. Those findings are encouraging for its use after cardiac surgery.

Delirium will be assessed by the Confusion Assessment Method for the ICU (CAM ICU) and the primary endpoint of the study is the occurrence of delirium in the first 7 days following surgery.

Enrollment: 348 patients

Sex: All

Ages: 65+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• patients aged 65 or more who undergo cardiac surgery on and off-pump: coronary artery bypass graft, cardiac valve replacement or both.
• Consent signed

Exclusion criteria

• history of mental illness, dementia
• inclusion in another study evaluating sedation or pain
• length of stay in ICU less than 24 hours
• alpha 2 agonists allergy
• surgery performed in an immediate emergency situation
• uncontrolled hypotension
• second and third degree atrioventricular block without pacemaker
• severe hepatic insufficiency
• acute cerebrovascular diseases
• patient treated with clonidine
• patient with disturbed preoperative liver assessment (hepatocellular insufficiency)
• patient under guardianship or curatorship

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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348 participants in 2 patient groups, including a placebo group

Dexmédétomidine

Active Comparator group

Description:

Intravenous infusion with electric syringe of Dexmedetomidine 0,4ug/ml. Rate 0,1ug/kg/h to 1,4ug/kg/h. Nightly infusion from 20:00 to 08:00. The drug is titrated to achieve RASS between -1 and 1. Modification of infusion rate by 0,1ug/kg/h is recommended with stabilization phase of 1 hour before another rate adjustment.

Treatment:

Drug: Dexmedetomidine

Sodium Chloride 0,9%

Placebo Comparator group

Description:

Intravenous infusion with electric syringe of normal saline. Rate modifications follow the same rules as in experimental group.

Treatment:

Drug: Sodium chloride 0.9%