Ignite Creation Date:
2024-05-06 @ 3:47 PM
Last Modification Date:
2024-10-26 @ 1:57 PM
Study NCT ID:
NCT04758936
Status:
UNKNOWN
Last Update Posted:
2021-02-17
First Post:
2021-02-10
Brief Title:
Clonidine vs Dexmedetomidine in Agitated Delirium in Intensive Care Patients
Sponsor:
Erasme University Hospital
Organization:
Erasme University Hospital
Study Overview
Official Title:
Effect of Clonidine vs Dexmedetomidine in Addition to Standard Treatment in Agitated Delirium in Intensive Care Patients Pilot Study
Status:
UNKNOWN
Status Verified Date:
2021-02
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
Clodex
Brief Summary:
Delirium is one of the most common manifestations of cerebral dysfunction in severely ill patients
The international guidelines for the prevention of delirium in intensive care recommend the daily application of environmental behavioral and pharmacological strategies In the case of the agitated form of delirium experts recommend the use of low-dose neuroleptics and α-2 agonists to control psychotic manifestations rather than traditional sedatives mainly benzodiazepines that can clearly aggravate delirium
Currently two pharmacological α-2 agonists clonidine Catapressan Boehringer Ingelheim and dexmedetomidine Dexdor Orion Corporation are marketed and commonly used in intensive care for their sedative anxiolytic and analgesic properties
To our knowledge no studies have compared the effects of clonidine and dexmedetomidine in agitated delirium in intensive care patients Therefore our goal is to compare the safety of clonidine and dexmedetomidine in terms of bradycardia and or hypotension in addition to standard treatment in the context of agitated delirium in intensive care patients
The international guidelines for the prevention of delirium in intensive care recommend the daily application of environmental behavioral and pharmacological strategies In the case of the agitated form of delirium experts recommend the use of low-dose neuroleptics and α-2 agonists to control psychotic manifestations rather than traditional sedatives mainly benzodiazepines that can clearly aggravate delirium
Currently two pharmacological α-2 agonists clonidine Catapressan Boehringer Ingelheim and dexmedetomidine Dexdor Orion Corporation are marketed and commonly used in intensive care for their sedative anxiolytic and analgesic properties
To our knowledge no studies have compared the effects of clonidine and dexmedetomidine in agitated delirium in intensive care patients Therefore our goal is to compare the safety of clonidine and dexmedetomidine in terms of bradycardia and or hypotension in addition to standard treatment in the context of agitated delirium in intensive care patients
Detailed Description:
Delirium is one of the most common manifestations of cerebral dysfunction in severely ill patients 60 to 80 of ventilated patients leading not only to short-term complications prolonged duration of ventilation prolonged hospital stay and increased mortality but also long-term repercussions in the form of impaired cognitive functions post-traumatic stress syndromes and decreased quality of life Different forms of delirium coexist some patients are very agitated while others are on the contrary in an apathetic state In intensive care patients the agitated form of delirium is particularly problematic because of the risk of self-extubation and removal of other critical medical devices
Pain stress anxiety and deregulation of wake sleep cycles are important risk factors for delirium occurrence and are unfortunately frequently encountered in varying degrees in intensive care
The international guidelines for the prevention of delirium in intensive care recommend the daily application of environmental behavioral and pharmacological strategies Thus the early mobilization of the patient the respect of the waking sleep cycles the adequate control of the pain represent effective measures of prevention These guidelines also emphasize the importance of minimal use of sedative treatments while ensuring the comfort and safety of patients
Finally in the case of the agitated form of delirium experts recommend the use of low-dose neuroleptics and α-2 agonists to control psychotic manifestations rather than traditional sedatives mainly benzodiazepines that can clearly aggravate delirium
The α-2 receptors constitute a family of receptors coupled to transmembrane G proteins with 3 pharmacological subtypes α-2A α-2B and α-2C The α-2A and α-2C subtypes are mainly found in the central nervous system Stimulation of these receptor subtypes may be responsible for sedation analgesia and sympatholytic effects Α-2B receptors are more common on vascular smooth muscle and have been shown to have vasopressor effects By their inhibitory action on adenylyl cyclase the 3 subtypes have several effects 1 they reduce the levels of cyclic adenosine monophosphate 2 they cause a hyperpolarization of noradrenergic neurons in the brain stem in particular in the locus ceruleus 3 they suppress the neural discharge This suppression inhibits the release of norepinephrine into the synapse resulting in a modulatory effect on the anxiety wakefulness and sleep of patients Activation of this negative feedback loop may also result in reduced heart rate and blood pressure by sympatholytic action
Currently two pharmacological α-2 agonists clonidine Catapressan Boehringer Ingelheim and dexmedetomidine Dexdor Orion Corporation are marketed and commonly used in intensive care for their sedative anxiolytic and analgesic properties Unlike traditional sedatives benzodiazepines and propofol that leave the patient unresponsive to stimuli or stupor sedation achieved by administering these α-2 agonists has several advantages The α-2 agonists lower the general level of alertness NREM indifference to the environment and pain but leave the waking ability intact Therefore under α-2 agonists patients are more easily awake until a return to full consciousness able to respond to simple orders participate in their sessions of physiotherapy and communicate within the limits of the presence of an intubation probe or non-invasive ventilation mask In addition these agents do not cause respiratory depression
Clonidine is an α-2 agonist that has an affinity of 2001 for α-2 receptors versus α-1 receptors Initially marketed for its antihypertensive properties clonidine is used in intensive care for its sedative and analgesic effects especially in the treatment of delirium or alcohol withdrawal syndromes alcohol opioids or benzodiazepines The pharmacodynamics of this α-2 agonist is characterized by hepatic metabolism and renal elimination The half-life elimination time is about 24 hours The doses administered ranged from 001 μg kg min to 003 μg kg min and the main reported side effects were bradycardia low blood pressure and dry mouth Pharmacodynamically clonidine has the advantage to be very affordable about 90 euros per patient for a week of treatment
Dexmedetomidine is the newest of the α-2 agonists Its affinity and specificity for α-2 receptors is much greater than that of clonidine 16001 α-2 α-1 receptors25 The pharmacodynamics of this α-2 agonist is characterized by hepatic metabolism and elimination almost completely renal The half-life elimination time is about 2 hours The recommended doses vary between 04 μg kg h and can be titrated up to 14 μg kg h The main reported side effects are bradycardia and low blood pressure Its cost on the other hand is much higher 800 euros per patient for a one week treatment The efficacy of dexmedetomidine has been demonstrated in terms of reduced mechanical ventilation time and ICU length of hospitalization when compared to placebo traditional sedatives propofol or benzodiazepines neuroletics in the context of critical care delirium
To date only one study has compared the effects of clonidine and dexmedetomidine in a prospective randomized manner n 70 in order to achieve short-term deep sedation in post-operative mechanical ventilation patients Study confirms sedative efficacy of α-2 agonists and suggests greater hemodynamic stability under dexmedetomidine
To our knowledge no studies have compared the effects of clonidine and dexmedetomidine in agitated delirium in intensive care patients Therefore our goal is to compare the safety of clonidine and dexmedetomidine in terms of bradycardia and or hypotension in addition to standard treatment in the context of agitated delirium in intensive care patients Bradycardia is defined by a heart rate 60 min or a decrease of 20 of the initial heart rate and arterial hypotension by one of the following criteria
systolic blood pressure less than 90mmHg or a decrease of 20 of the initial systolic arterial pressure
initiation of a vasopressor treatment
10 increase in the dose of vasopressor treatment if already started
Pain stress anxiety and deregulation of wake sleep cycles are important risk factors for delirium occurrence and are unfortunately frequently encountered in varying degrees in intensive care
The international guidelines for the prevention of delirium in intensive care recommend the daily application of environmental behavioral and pharmacological strategies Thus the early mobilization of the patient the respect of the waking sleep cycles the adequate control of the pain represent effective measures of prevention These guidelines also emphasize the importance of minimal use of sedative treatments while ensuring the comfort and safety of patients
Finally in the case of the agitated form of delirium experts recommend the use of low-dose neuroleptics and α-2 agonists to control psychotic manifestations rather than traditional sedatives mainly benzodiazepines that can clearly aggravate delirium
The α-2 receptors constitute a family of receptors coupled to transmembrane G proteins with 3 pharmacological subtypes α-2A α-2B and α-2C The α-2A and α-2C subtypes are mainly found in the central nervous system Stimulation of these receptor subtypes may be responsible for sedation analgesia and sympatholytic effects Α-2B receptors are more common on vascular smooth muscle and have been shown to have vasopressor effects By their inhibitory action on adenylyl cyclase the 3 subtypes have several effects 1 they reduce the levels of cyclic adenosine monophosphate 2 they cause a hyperpolarization of noradrenergic neurons in the brain stem in particular in the locus ceruleus 3 they suppress the neural discharge This suppression inhibits the release of norepinephrine into the synapse resulting in a modulatory effect on the anxiety wakefulness and sleep of patients Activation of this negative feedback loop may also result in reduced heart rate and blood pressure by sympatholytic action
Currently two pharmacological α-2 agonists clonidine Catapressan Boehringer Ingelheim and dexmedetomidine Dexdor Orion Corporation are marketed and commonly used in intensive care for their sedative anxiolytic and analgesic properties Unlike traditional sedatives benzodiazepines and propofol that leave the patient unresponsive to stimuli or stupor sedation achieved by administering these α-2 agonists has several advantages The α-2 agonists lower the general level of alertness NREM indifference to the environment and pain but leave the waking ability intact Therefore under α-2 agonists patients are more easily awake until a return to full consciousness able to respond to simple orders participate in their sessions of physiotherapy and communicate within the limits of the presence of an intubation probe or non-invasive ventilation mask In addition these agents do not cause respiratory depression
Clonidine is an α-2 agonist that has an affinity of 2001 for α-2 receptors versus α-1 receptors Initially marketed for its antihypertensive properties clonidine is used in intensive care for its sedative and analgesic effects especially in the treatment of delirium or alcohol withdrawal syndromes alcohol opioids or benzodiazepines The pharmacodynamics of this α-2 agonist is characterized by hepatic metabolism and renal elimination The half-life elimination time is about 24 hours The doses administered ranged from 001 μg kg min to 003 μg kg min and the main reported side effects were bradycardia low blood pressure and dry mouth Pharmacodynamically clonidine has the advantage to be very affordable about 90 euros per patient for a week of treatment
Dexmedetomidine is the newest of the α-2 agonists Its affinity and specificity for α-2 receptors is much greater than that of clonidine 16001 α-2 α-1 receptors25 The pharmacodynamics of this α-2 agonist is characterized by hepatic metabolism and elimination almost completely renal The half-life elimination time is about 2 hours The recommended doses vary between 04 μg kg h and can be titrated up to 14 μg kg h The main reported side effects are bradycardia and low blood pressure Its cost on the other hand is much higher 800 euros per patient for a one week treatment The efficacy of dexmedetomidine has been demonstrated in terms of reduced mechanical ventilation time and ICU length of hospitalization when compared to placebo traditional sedatives propofol or benzodiazepines neuroletics in the context of critical care delirium
To date only one study has compared the effects of clonidine and dexmedetomidine in a prospective randomized manner n 70 in order to achieve short-term deep sedation in post-operative mechanical ventilation patients Study confirms sedative efficacy of α-2 agonists and suggests greater hemodynamic stability under dexmedetomidine
To our knowledge no studies have compared the effects of clonidine and dexmedetomidine in agitated delirium in intensive care patients Therefore our goal is to compare the safety of clonidine and dexmedetomidine in terms of bradycardia and or hypotension in addition to standard treatment in the context of agitated delirium in intensive care patients Bradycardia is defined by a heart rate 60 min or a decrease of 20 of the initial heart rate and arterial hypotension by one of the following criteria
systolic blood pressure less than 90mmHg or a decrease of 20 of the initial systolic arterial pressure
initiation of a vasopressor treatment
10 increase in the dose of vasopressor treatment if already started
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None