ICU DeliriumPhase 3EXACTUMNCT03477344
Dexmedetomidine After Cardiac Surgery for Prevention of Delirium
A Phase 3 study testing Dexmedetomidine and Sodium chloride 0.9% in people with ICU Delirium, run by University Hospital, Brest at 9 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- ICU Delirium
- What is being tested?
- Dexmedetomidine and Sodium chloride 0.9%
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 348 participants
- Where
- 9 sitesFrance
- Study dates
- 4 Jan 2019to 29 Jun 2021
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- patients aged 65 or more who undergo cardiac surgery on and off-pump: coronary artery bypass graft, cardiac valve replacement or both.
- Consent signed
- length of stay in ICU less than 24 hours
- alpha 2 agonists allergy
- surgery performed in an immediate emergency situation
- uncontrolled hypotension
Show all 12Show fewer
- 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
Who cannot join
- history of mental illness, dementia
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
France9 sites
Angers university hospital
Angers
CHRU de Brest
Brest, 29609
Clermont Ferrand university hospital
Clermont-Ferrand
CHU de Grenoble
Grenoble, 38000
Hôpital Privé Jacques Cartier
Massy
CHU de Nantes
Nantes, 5600
CHU la Pitié Salpétrière
Paris, 75000
CHU Poitiers
Poitiers, 86000
CHU de Rennes
Rennes, 22000
About this study
Official title: Dexmedetomidine After Cardiac Surgery for Prevention of Delirium: The Exactum Study a Randomised Double Blind Controlled Trial
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.
Read the 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.
- Conditions
- ICU Delirium
- Being tested
- Dexmedetomidine, Sodium chloride 0.9%
- Keywords
- Cardiac Surgery, Delirium, Sleep deprivation
- Medical subject headings
- Delirium, Sleep Deprivation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexmedetomidineDrug
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.
Sodium chloride 0.9%Drug
Intravenous infusion with electric syringe of normal saline. Rate modifications follow the same rules as in experimental group.
| Study group | Role | What they receive |
|---|---|---|
| Dexmédétomidine | Active comparator | 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. Receives: Drug: Dexmedetomidine |
| Sodium Chloride 0,9% | Placebo comparator | Intravenous infusion with electric syringe of normal saline. Rate modifications follow the same rules as in experimental group. Receives: Drug: Sodium chloride 0.9% |
What is being measured
The primary outcome is the main question the study is designed to answer.
Delirium
Occurrence of delirium diagnosed by the Confusion Assessment Method (CAM ICU) at any time in the first seven days after surgery
Measured: 7 days
Secondary outcomes (15)
agitation with be assessed using the Richmond agitation and sedation score
Score Term Description
- 4 Combative Overtly combative or violent; immediate danger to staff
- 3 Very agitated Pulls on or removes tube(s) or catheter(s) or has aggressive behavior toward staff
- 2 Agitated Frequent nonpurposeful movement or patient-ventilator dyssynchrony
- 1 Restless Anxious or apprehensive but movements not aggressive or vigorous 0 Alert and calm Spontaneously pays attention to caregiver
- 1 Drowsy Not fully alert, but has sustained (more than 10 seconds) awakening, with eye contact, to voice
- 2 Light sedation Briefly (less than 10 seconds) awakens with eye contact to voice
- 3 Moderate sedation Any movement (but no eye contact) to voice
- 4 Deep sedation No response to voice, but any movement to physical stimulation
- 5 Unarousable No response to voice or physical stimulation
Measured: 7 days
length of ICU stay
Lenght of patient's ICU stay
Measured: 28 days
length of hospital stay
Length of Patient's hospital stay
Measured: 28 days
quality of life 3 months after surgery with the The Short Form (36) Health Survey score
The Short Form (36) Health Survey is a 36-item, patient-reported survey of patient health. The SF-36 is a measure of health status and an abbreviated variant of it, the SF-6D, is commonly used in health economics as a variable in the quality-adjusted life year calculation to determine the cost-effectiveness of a health treatment. The original SF-36 came out from the Medical Outcome Study, MOS, done by the RAND Corporation. Since then a group of researchers from the original study released a commercial version of SF-36 while the original SF-36 is available in public domain license free from RAND.
Measured: 90 days
cognitive capacity 3 months after surgery evaluated with the Cognitive Failures Questionnnaire (CFQ)
The Cognitive Failures Questionnaire is a self-report scale that taps failures in everyday actions, perception and attention, and memory over the last month. It consists of 25 items that are scored on a 5-point scale (0=never; 4=very often). Illustrative items are 'Do you fail to notice signposts on the road?' and 'Do you forget where you put something like a newspaper or a book?' Scores are summed to obtain a total CFQ score varying from 0 to 100, with higher scores indicating more self-reported cognitive failures.
Measured: 90 days
agitation related adverse events onset and number
-self-extubation
Measured: 7 days
agitation related adverse events onset and number
-catheter or medical devices removal (drains, urinary catheter, arterial and central venous catheters, externenal pacemaker)
Measured: 7 days
agitation related adverse events onset and number
-fall of bed
Measured: 7 days
agitation related adverse events onset and number
-getaway
Measured: 7 days
agitation related adverse events onset and number
-contention removal
Measured: 7 days
agitation related adverse events onset and number
-aggressive acts
Measured: 7 days
Self-assessment of sleep quality
Assessment by a numerical scale from 0 to 10 and the Leeds Sleep questionnaire
Measured: 7 days
Intra hospital mortality and Mortality at 3 months of surgery
Measured: 3 months
Cognitive capacity
Cognitive capacity assessed by Cognitive Failures Questionnaire (CFQ) at 3 months of surgery
Measured: 3 months
Post-traumatic stress disorder
Post-traumatic stress disorder assessed by the PCL-5 questionnaire at 3 months of surgery
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Mar 2018
- Study start4 Jan 2019
- Primary completion29 Jun 2021
- Study completion29 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for ICU DeliriumStudies of the same condition, open and under way.
- More trials run by University Hospital, BrestThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 348 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Brest
- Sponsor type
- University, hospital or other
- Collaborators
- Direction Générale de l'Offre de Soins, Baxter Healthcare Corporation
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03477344
- Sponsor's protocol ID
- 29BRC18.0051 (EXACTUM)
- Acronym
- EXACTUM
- Status last verified
- Jun 2022
- First submitted
- 6 Mar 2018
- Last updated
- 22 Jun 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All collected data that underlie results in a publication
Publications
Huet O, Gargadennec T, Oilleau JF, Rozec B, Nesseler N, Bougle A, Kerforne T, Lasocki S, Eljezi V, Dessertaine G, Amour J, Chapalain X; EXACTUM and the Atlanrea Study Group. Prevention of post-operative delirium using an overnight infusion of dexmedetomidine in patients undergoing cardiac surgery: a pragmatic, randomized, double-blind, placebo-controlled trial. Crit Care. 2024 Feb 29;28(1):64. doi: 10.1186/s13054-024-04842-1.
PubMed 38419119Gargadennec 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.
PubMed 35396310
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dexmedetomidine After Cardiac Surgery for Prevention of Delirium: The Exactum Study a Randomised Double Blind Controlled Trial
- ClinicalTrials.gov ID
- NCT03477344
- Acronym / sponsor ID
- EXACTUM / 29BRC18.0051 (EXACTUM)
- Conditions
- ICU Delirium
- Keywords
- Cardiac Surgery, Delirium, Sleep deprivation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 348 participants (actual)
- Lead sponsor
- University Hospital, BrestUniversity, hospital or other
- Collaborators
- Direction Générale de l'Offre de Soins, Baxter Healthcare Corporation
- Study start
- 4 Jan 2019 (actual)
- Primary completion
- 29 Jun 2021 (actual)
- Study completion
- 29 Jun 2021 (actual)
- First posted
- 26 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dexmédétomidine | Active comparator | Drug: DexmedetomidineIntravenous 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. |
| Sodium Chloride 0,9% | Placebo comparator | Drug: Sodium chloride 0.9%Intravenous infusion with electric syringe of normal saline. Rate modifications follow the same rules as in experimental group. |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (12 listed)
- patients aged 65 or more who undergo cardiac surgery on and off-pump: coronary artery bypass graft, cardiac valve replacement or both.
- Consent signed
- length of stay in ICU less than 24 hours
- alpha 2 agonists allergy
- surgery performed in an immediate emergency situation
Key exclusion criteria (1 listed)
- history of mental illness, dementia
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DexmedetomidineIntravenous 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. | Drug | Dexmédétomidine |
| Sodium chloride 0.9%Intravenous infusion with electric syringe of normal saline. Rate modifications follow the same rules as in experimental group. | Drug | Sodium Chloride 0,9% |
Primary outcome
Delirium
Time frame: 7 days
Occurrence of delirium diagnosed by the Confusion Assessment Method (CAM ICU) at any time in the first seven days after surgery
15 secondary outcomes
agitation with be assessed using the Richmond agitation and sedation score
Time frame: 7 days
length of ICU stay
Time frame: 28 days
length of hospital stay
Time frame: 28 days
quality of life 3 months after surgery with the The Short Form (36) Health Survey score
Time frame: 90 days
cognitive capacity 3 months after surgery evaluated with the Cognitive Failures Questionnnaire (CFQ)
Time frame: 90 days
agitation related adverse events onset and number
Time frame: 7 days
agitation related adverse events onset and number
Time frame: 7 days
agitation related adverse events onset and number
Time frame: 7 days
agitation related adverse events onset and number
Time frame: 7 days
agitation related adverse events onset and number
Time frame: 7 days
agitation related adverse events onset and number
Time frame: 7 days
Self-assessment of sleep quality
Time frame: 7 days
Intra hospital mortality and Mortality at 3 months of surgery
Time frame: 3 months
Cognitive capacity
Time frame: 3 months
Post-traumatic stress disorder
Time frame: 3 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2022.
- Derived from this study: PubMed 38419119Huet O, Gargadennec T, Oilleau JF, Rozec B, Nesseler N, Bougle A, Kerforne T, Lasocki S, Eljezi V, Dessertaine G, Amour J, Chapalain X; EXACTUM and the Atlanrea Study Group. Prevention of post-operative delirium using an overnight infusion of dexmedetomidine in patients undergoing cardiac surgery: a pragmatic, randomized, double-blind, placebo-controlled trial. Crit Care. 2024 Feb 29;28(1):64. doi: 10.1186/s13054-024-04842-1.
- Derived from this study: PubMed 35396310Gargadennec 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.
- Individual participant dataSharing planned: Yes. All collected data that underlie results in a publication
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Delirium
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Dexmedetomidine and Sodium chloride 0.9% in people with ICU Delirium, run by University Hospital, Brest at 9 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Delirium (time frame: 7 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03477344, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2022.