Cardiac Surgical ProceduresPhase 4LOWDEXDELNCT03388541
Low Dose Dexmedetomidine and Delirium After Cardiac Surgery
A Phase 4 study testing Dexmedetomidine in people with Cardiac Surgical Procedures, run by Cliniques universitaires Saint-Luc- Université Catholique de Louvain at 1 site in Belgium.
Trial summary
Delirium after cardiac surgery can occur in up to 50% of the patients and has been shown to be significantly associated with increased morbidity and mortality. Advanced age is a significant risk factor of delirium. Read more about this study
- Who is it for?
- Ages 60 to 90 years
- Conditions the study is for
- Cardiac Surgical Procedures
- What is being tested?
- Dexmedetomidine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 420 participants
- Where
- 1 siteBelgium
- Study dates
- 17 Jan 2018to 12 Aug 2019
- Phase
- Phase 4
- 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 60 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients undergoing cardiac surgery with cardiopulmonary bypass
Who cannot join
- Hepatic dysfunction (hepatic function tests 3 times the normal value)
- Preoperative renal replacement therapy
- Preoperative delirium
- Emergency surgery not allowing neurologic evaluation by MMSE
- Mini invasive cardiac surgery
- Patients not speaking French
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Does LOW Dose DEXmedetomidine After Cardiopulmonary Bypass Separation Decrease the Incidence of DELirium: A Double-blind Randomized Placebo-controlled Study (LOWDEXDEL Study)
Delirium after cardiac surgery can occur in up to 50% of the patients and has been shown to be significantly associated with increased morbidity and mortality. Advanced age is a significant risk factor of delirium.
Numerous studies have shown that sedation with high doses of Dexmedetomidine in the ICU reduces the incidence of postoperative delirium. On the other hand animal studies have shown neuroprotective effects of Dexmedetomidine by means of stimulating alpha2A-adrenoceptors.
It is not clear whether the administration of a low dose Dexmedetomidine in cardiac surgery would have any neuroprotective effects by stimulating the alpha 2A-receptors and as such would decrease the incidence of postoperative delirium.
Read the detailed description
Postoperative delirium (PD) is a common problem in cardiac surgical patients. Its incidence varies among studies and can reach up to 50% of the patients. PD is associated with increased morbidity and mortality. Its occurrence is the resultant between the predisposing factors and the precipitating factors. Age seems to be a significant predisposing factor. In this regard the pathophysiology of PD is not yet fully understood. There are several hypothetical mechanisms for the development of PD. The first hypothesis is cerebral ischemia and BBB breakdown. The second hypothesis is neuro-inflammation. Peripheral pro-inflammatory mediators especially released during surgery would interact with the brain. Otherwise there is the problem of sleep deprivation/fragmentation in patients admitted to the hospital.
Dexmedetomidine is a potent and more selective alpha2-adrenergic receptor than clonidine. Studies have demonstrated that it has neuroprotective and anti-inflammatory actions.
Numerous studies including trials in cardiac surgery have shown a decreased incidence of delirium when Dexmedetomidine was used as sedative in the ICU compared with other sedatives acting on the GABA receptors. However, in these studies high doses of Dexmedetomidine were used for periods up to 24h. Dexmedetomidine was started in the ICU and was not compared in a double-blind fashion with placebo. In a recent randomized double-blind placebo-controlled trial a very low dose of Dexmedetomidine decreased the occurrence of PD when compared to placebo. However this study was performed in non-cardiac patients. Moreover the patients were included after their arrival in the ICU, which means that those patients who were intubated at their arrival in the ICU were not included. And again the study medication was only started after arrival in the ICU.
The aim of this study is to elucidate whether the administration of Dexmedetomidine at a low dose would decrease the incidence of PD in elderly patients undergoing cardiac surgery. The hypothesis is that Dexmedetomidine at low doses, by only stimulating the alpha2A adrenoceptors,would have neuroprotective affects ans as such decrease the incidence of PD. Dexmedetomidine would also have anti-inflammatory effects and effects on the quality of sleep. Both mechanisms would play a role in the pathophysiology of PD.
- Conditions
- Cardiac Surgical Procedures
- Being tested
- Dexmedetomidine, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexmedetomidineDrug
Dexmedetomidine will be started at 5mL/h while the patient is still in the operating room. The patient will be transferred to the intensive care unit with a sedative regimen based on propofol.
PlaceboDrug
A continuous infusion of NaCL 0.9% will be started at 5mL/h while the patient is still in the operating room. The patient will be transferred to the intensive care unit with a sedative regimen based on propofol.
| Study group | Role | What they receive |
|---|---|---|
| Dexmedetomidine | Active comparator | Dexmedetomidine will be administered at 0.4ug/kg/h (5mL/h) starting at the closure of the chest and continued during 10h. Receives: Drug: Dexmedetomidine |
| Placebo | Placebo comparator | NaCl 0.9% will be administered at 5mL/h starting at the closure of the chest and continued during 10h. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The incidence of delirium
The incidence of delirium detected by means of CAM-ICU and CAM
Measured: Through study completion, an average of 30 days
Secondary outcomes (8)
Number of days spent in delirium
Total number of days in a delirious state
Measured: Through study completion, an average of 30 days
ICU stay
The duration of days admitted in the ICU and in the hospital
Measured: Through study completion, an average of 30 days
Total dose of analgesics
Total dose of analgesics used in the ICU
Measured: Through study completion, an average of 30 days
Total dose of vasopressors
Total dose of vasopressors used in the ICU
Measured: Through study completion, an average of 30 days
Pace maker necessitation
Number of patients needing external pacing
Measured: Through study completion, an average of 30 days
Hospital stay
The duration of days admitted in the hospital
Measured: Through study completion, an average of 30 days
Total dose sedatives
Total dose of sedatives used in the ICU
Measured: Through study completion, an average of 30 days
Total dose of inotropic agents
Total dose of inotropic agents used in the ICU
Measured: Through study completion, an average of 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jan 2018
- Study start17 Jan 2018
- Primary completion12 Aug 2019
- Study completion12 Aug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Cardiac Surgical ProceduresStudies of the same condition, open and under way.
- More trials run by Cliniques universitaires Saint-Luc- Université Catholique de LouvainThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 420 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mona Momeni, MD, PhD, Cliniques universitaires Saint-Luc- Université Catholique de Louvain
- Investigators
- Mona Momeni, MD,PhD, Principal investigator, Cliniques universitaires Saint-Luc- Université Catholique de Louvain
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03388541
- Sponsor's protocol ID
- 2017/24JUL/374
- Acronym
- LOWDEXDEL
- Status last verified
- Sep 2020
- First submitted
- 1 Aug 2017
- Last updated
- 30 Sep 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Paris A, Mantz J, Tonner PH, Hein L, Brede M, Gressens P. The effects of dexmedetomidine on perinatal excitotoxic brain injury are mediated by the alpha2A-adrenoceptor subtype. Anesth Analg. 2006 Feb;102(2):456-61. doi: 10.1213/01.ane.0000194301.79118.e9.
PubMed 16428542Maier C, Steinberg GK, Sun GH, Zhi GT, Maze M. Neuroprotection by the alpha 2-adrenoreceptor agonist dexmedetomidine in a focal model of cerebral ischemia. Anesthesiology. 1993 Aug;79(2):306-12. doi: 10.1097/00000542-199308000-00016.
PubMed 8102042Jiang L, Hu M, Lu Y, Cao Y, Chang Y, Dai Z. The protective effects of dexmedetomidine on ischemic brain injury: A meta-analysis. J Clin Anesth. 2017 Aug;40:25-32. doi: 10.1016/j.jclinane.2017.04.003. Epub 2017 Apr 17.
PubMed 28625441Tasdogan M, Memis D, Sut N, Yuksel M. Results of a pilot study on the effects of propofol and dexmedetomidine on inflammatory responses and intraabdominal pressure in severe sepsis. J Clin Anesth. 2009 Sep;21(6):394-400. doi: 10.1016/j.jclinane.2008.10.010.
PubMed 19833271Su X, Meng ZT, Wu XH, Cui F, Li HL, Wang DX, Zhu X, Zhu SN, Maze M, Ma D. Dexmedetomidine for prevention of delirium in elderly patients after non-cardiac surgery: a randomised, double-blind, placebo-controlled trial. Lancet. 2016 Oct 15;388(10054):1893-1902. doi: 10.1016/S0140-6736(16)30580-3. Epub 2016 Aug 16.
PubMed 27542303Shehabi Y, Grant P, Wolfenden H, Hammond N, Bass F, Campbell M, Chen J. Prevalence of delirium with dexmedetomidine compared with morphine based therapy after cardiac surgery: a randomized controlled trial (DEXmedetomidine COmpared to Morphine-DEXCOM Study). Anesthesiology. 2009 Nov;111(5):1075-84. doi: 10.1097/ALN.0b013e3181b6a783.
PubMed 19786862Djaiani G, Silverton N, Fedorko L, Carroll J, Styra R, Rao V, Katznelson R. Dexmedetomidine versus Propofol Sedation Reduces Delirium after Cardiac Surgery: A Randomized Controlled Trial. Anesthesiology. 2016 Feb;124(2):362-8. doi: 10.1097/ALN.0000000000000951.
PubMed 26575144Momeni M, Khalifa C, Lemaire G, Watremez C, Tircoveanu R, Van Dyck M, Kahn D, Rosal Martins M, Mastrobuoni S, De Kerchove L, Zango SH, Jacquet LM. Propofol plus low-dose dexmedetomidine infusion and postoperative delirium in older patients undergoing cardiac surgery. Br J Anaesth. 2021 Mar;126(3):665-673. doi: 10.1016/j.bja.2020.10.041. Epub 2020 Dec 24.
PubMed 33358336
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Does LOW Dose DEXmedetomidine After Cardiopulmonary Bypass Separation Decrease the Incidence of DELirium: A Double-blind Randomized Placebo-controlled Study (LOWDEXDEL Study)
- ClinicalTrials.gov ID
- NCT03388541
- Acronym / sponsor ID
- LOWDEXDEL / 2017/24JUL/374
- Conditions
- Cardiac Surgical Procedures
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 420 participants (actual)
- Lead sponsor
- Cliniques universitaires Saint-Luc- Université Catholique de LouvainUniversity, hospital or other
- Study start
- 17 Jan 2018 (actual)
- Primary completion
- 12 Aug 2019 (actual)
- Study completion
- 12 Aug 2019 (actual)
- First posted
- 3 Jan 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.
Delirium after cardiac surgery can occur in up to 50% of the patients and has been shown to be significantly associated with increased morbidity and mortality. Advanced age is a significant risk factor of delirium.
Numerous studies have shown that sedation with high doses of Dexmedetomidine in the ICU reduces the incidence of postoperative delirium. On the other hand animal studies have shown neuroprotective effects of Dexmedetomidine by means of stimulating alpha2A-adrenoceptors.
It is not clear whether the administration of a low dose Dexmedetomidine in cardiac surgery would have any neuroprotective effects by stimulating the alpha 2A-receptors and as such would decrease the incidence of postoperative delirium.
Detailed description
Postoperative delirium (PD) is a common problem in cardiac surgical patients. Its incidence varies among studies and can reach up to 50% of the patients. PD is associated with increased morbidity and mortality. Its occurrence is the resultant between the predisposing factors and the precipitating factors. Age seems to be a significant predisposing factor. In this regard the pathophysiology of PD is not yet fully understood. There are several hypothetical mechanisms for the development of PD. The first hypothesis is cerebral ischemia and BBB breakdown. The second hypothesis is neuro-inflammation. Peripheral pro-inflammatory mediators especially released during surgery would interact with the brain. Otherwise there is the problem of sleep deprivation/fragmentation in patients admitted to the hospital.
Dexmedetomidine is a potent and more selective alpha2-adrenergic receptor than clonidine. Studies have demonstrated that it has neuroprotective and anti-inflammatory actions.
Numerous studies including trials in cardiac surgery have shown a decreased incidence of delirium when Dexmedetomidine was used as sedative in the ICU compared with other sedatives acting on the GABA receptors. However, in these studies high doses of Dexmedetomidine were used for periods up to 24h. Dexmedetomidine was started in the ICU and was not compared in a double-blind fashion with placebo. In a recent randomized double-blind placebo-controlled trial a very low dose of Dexmedetomidine decreased the occurrence of PD when compared to placebo. However this study was performed in non-cardiac patients. Moreover the patients were included after their arrival in the ICU, which means that those patients who were intubated at their arrival in the ICU were not included. And again the study medication was only started after arrival in the ICU.
The aim of this study is to elucidate whether the administration of Dexmedetomidine at a low dose would decrease the incidence of PD in elderly patients undergoing cardiac surgery. The hypothesis is that Dexmedetomidine at low doses, by only stimulating the alpha2A adrenoceptors,would have neuroprotective affects ans as such decrease the incidence of PD. Dexmedetomidine would also have anti-inflammatory effects and effects on the quality of sleep. Both mechanisms would play a role in the pathophysiology of PD.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dexmedetomidine | Active comparator | Drug: DexmedetomidineDexmedetomidine will be administered at 0.4ug/kg/h (5mL/h) starting at the closure of the chest and continued during 10h. |
| Placebo | Placebo comparator | Drug: PlaceboNaCl 0.9% will be administered at 5mL/h starting at the closure of the chest and continued during 10h. |
Who may qualify
- Ages
- 60 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Patients undergoing cardiac surgery with cardiopulmonary bypass
Key exclusion criteria (6 listed)
- Hepatic dysfunction (hepatic function tests 3 times the normal value)
- Preoperative renal replacement therapy
- Preoperative delirium
- Emergency surgery not allowing neurologic evaluation by MMSE
- Mini invasive cardiac surgery
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 |
|---|---|---|
| DexmedetomidineDexmedetomidine will be started at 5mL/h while the patient is still in the operating room. The patient will be transferred to the intensive care unit with a sedative regimen based on propofol. | Drug | Dexmedetomidine |
| PlaceboA continuous infusion of NaCL 0.9% will be started at 5mL/h while the patient is still in the operating room. The patient will be transferred to the intensive care unit with a sedative regimen based on propofol. | Drug | Placebo |
Primary outcome
The incidence of delirium
Time frame: Through study completion, an average of 30 days
The incidence of delirium detected by means of CAM-ICU and CAM
8 secondary outcomes
Number of days spent in delirium
Time frame: Through study completion, an average of 30 days
ICU stay
Time frame: Through study completion, an average of 30 days
Total dose of analgesics
Time frame: Through study completion, an average of 30 days
Total dose of vasopressors
Time frame: Through study completion, an average of 30 days
Pace maker necessitation
Time frame: Through study completion, an average of 30 days
Hospital stay
Time frame: Through study completion, an average of 30 days
Total dose sedatives
Time frame: Through study completion, an average of 30 days
Total dose of inotropic agents
Time frame: Through study completion, an average of 30 days
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 30 Sep 2020.
- Background: PubMed 16428542Paris A, Mantz J, Tonner PH, Hein L, Brede M, Gressens P. The effects of dexmedetomidine on perinatal excitotoxic brain injury are mediated by the alpha2A-adrenoceptor subtype. Anesth Analg. 2006 Feb;102(2):456-61. doi: 10.1213/01.ane.0000194301.79118.e9.
- Background: PubMed 8102042Maier C, Steinberg GK, Sun GH, Zhi GT, Maze M. Neuroprotection by the alpha 2-adrenoreceptor agonist dexmedetomidine in a focal model of cerebral ischemia. Anesthesiology. 1993 Aug;79(2):306-12. doi: 10.1097/00000542-199308000-00016.
- Background: PubMed 28625441Jiang L, Hu M, Lu Y, Cao Y, Chang Y, Dai Z. The protective effects of dexmedetomidine on ischemic brain injury: A meta-analysis. J Clin Anesth. 2017 Aug;40:25-32. doi: 10.1016/j.jclinane.2017.04.003. Epub 2017 Apr 17.
- Background: PubMed 19833271Tasdogan M, Memis D, Sut N, Yuksel M. Results of a pilot study on the effects of propofol and dexmedetomidine on inflammatory responses and intraabdominal pressure in severe sepsis. J Clin Anesth. 2009 Sep;21(6):394-400. doi: 10.1016/j.jclinane.2008.10.010.
- Background: PubMed 27542303Su X, Meng ZT, Wu XH, Cui F, Li HL, Wang DX, Zhu X, Zhu SN, Maze M, Ma D. Dexmedetomidine for prevention of delirium in elderly patients after non-cardiac surgery: a randomised, double-blind, placebo-controlled trial. Lancet. 2016 Oct 15;388(10054):1893-1902. doi: 10.1016/S0140-6736(16)30580-3. Epub 2016 Aug 16.
- Background: PubMed 19786862Shehabi Y, Grant P, Wolfenden H, Hammond N, Bass F, Campbell M, Chen J. Prevalence of delirium with dexmedetomidine compared with morphine based therapy after cardiac surgery: a randomized controlled trial (DEXmedetomidine COmpared to Morphine-DEXCOM Study). Anesthesiology. 2009 Nov;111(5):1075-84. doi: 10.1097/ALN.0b013e3181b6a783.
- Background: PubMed 26575144Djaiani G, Silverton N, Fedorko L, Carroll J, Styra R, Rao V, Katznelson R. Dexmedetomidine versus Propofol Sedation Reduces Delirium after Cardiac Surgery: A Randomized Controlled Trial. Anesthesiology. 2016 Feb;124(2):362-8. doi: 10.1097/ALN.0000000000000951.
- Derived from this study: PubMed 33358336Momeni M, Khalifa C, Lemaire G, Watremez C, Tircoveanu R, Van Dyck M, Kahn D, Rosal Martins M, Mastrobuoni S, De Kerchove L, Zango SH, Jacquet LM. Propofol plus low-dose dexmedetomidine infusion and postoperative delirium in older patients undergoing cardiac surgery. Br J Anaesth. 2021 Mar;126(3):665-673. doi: 10.1016/j.bja.2020.10.041. Epub 2020 Dec 24.
- Individual participant dataSharing planned: No
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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.
Mona Momeni, MD,PhD principal investigator
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Dexmedetomidine in people with Cardiac Surgical Procedures, run by Cliniques universitaires Saint-Luc- Université Catholique de Louvain at 1 site in Belgium.
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 1 inclusion and 6 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 30 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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?
The incidence of delirium (time frame: Through study completion, an average of 30 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 NCT03388541, which also lists 8 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 30 Sep 2020.