Clinical trial NCT03477344: Dexmedetomidine After Cardiac Surgery for Prevention of Delirium
Official title: Dexmedetomidine After Cardiac Surgery for Prevention of Delirium: The Exactum Study a Randomised Double Blind Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: ICU Delirium
Keywords: Cardiac Surgery
Delirium
Sleep deprivation
Lead sponsor: University Hospital, Brest
Sponsor class: OTHER
Collaborators: name: Direction Générale de l'Offre de Soins
name: Baxter Healthcare Corporation
First posted: 2018-03-26
Enrollment: 348
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Delirium
timeFrame: 7 days
Secondary outcomes:
measure: agitation with be assessed using the Richmond agitation and sedation score
timeFrame: 7 days
measure: length of ICU stay
timeFrame: 28 days
measure: length of hospital stay
timeFrame: 28 days
measure: quality of life 3 months after surgery with the The Short Form (36) Health Survey score
timeFrame: 90 days
measure: cognitive capacity 3 months after surgery evaluated with the Cognitive Failures Questionnnaire (CFQ)
timeFrame: 90 days
measure: agitation related adverse events onset and number
timeFrame: 7 days
measure: agitation related adverse events onset and number
timeFrame: 7 days
measure: agitation related adverse events onset and number
timeFrame: 7 days
measure: agitation related adverse events onset and number
timeFrame: 7 days
measure: agitation related adverse events onset and number
timeFrame: 7 days
measure: agitation related adverse events onset and number
timeFrame: 7 days
measure: Self-assessment of sleep quality
timeFrame: 7 days
measure: Intra hospital mortality and Mortality at 3 months of surgery
timeFrame: 3 months
measure: Cognitive capacity
timeFrame: 3 months
measure: Post-traumatic stress disorder
timeFrame: 3 months
Other outcomes:
Locations:
city: Angers
country: France
facility: Angers university hospital
city: Brest
country: France
facility: CHRU de Brest
city: Clermont-Ferrand
country: France
facility: Clermont Ferrand university hospital
city: Grenoble
country: France
facility: CHU de Grenoble
city: Massy
country: France
facility: Hôpital Privé Jacques Cartier
city: Nantes
country: France
facility: CHU de Nantes
city: Paris
country: France
facility: CHU la Pitié Salpétrière
city: Poitiers
country: France
facility: CHU Poitiers
city: Rennes
country: France
facility: CHU de Rennes
Study officials:
References:
citation: Gargadennec T, Oilleau JF, Rozec B, Nesseler N, Lasocki S, Futier E, Amour J, Durand M, Bougle A, Kerforne T, Consigny M, Eddi D, Huet O. Dexmedetomidine after Cardiac Surgery for Prevention of Delirium (EXACTUM) trial protocol: a multicentre randomised, double-blind, placebo-controlled trial. BMJ Open. 2022 Apr 8;12(4):e058968. doi: 10.1136/bmjopen-2021-058968.