Clonidine vs. Dexmedetomidine in Agitated Delirium in Intensive Care Patients

NCT04758936 | Unknown Phase 4

• 1 other identifier: P2020/421
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 3

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.

Conditions

Delirium; Critical Illness

Keywords

Clonidine; Dexmedetomidine; Delirium; intensive care

Outcome Measures

Primary Outcomes (1)

• hemodynamic tolerance

  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 o(r 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

  Up to 7 days

Secondary Outcomes (11)

• number of living days without ventilation over 28 days

  Up to 28 days

• time to obtain a sedative sedation score (NICS -1 to 1)

  up to 7 days

• time to obtain a first CAM-ICU test indicating the absence of delirium

  Up to 7 days

• duration of delirium by evaluation CAM-ICU

  Up to 7 days

• use of other sedative and psychotropic medications (number and total doses)

  Up to 7 days

Study Arms (2)

Clonidine

EXPERIMENTAL

Given that agitated delirium requires rapid medical intervention, α-2 agonist therapy (clonidine) will be administered as soon as possible, The sedative and analgesic treatments will be administered and titrated according to the scales on the usual protocol of the service (evaluation of sedation (NICS) and analgesia (VAS, BPS, BPS-NI). In case of excessive sedation assessed by the scores and administration of combined treatments (α-2 agonist and other sedatives), the reduction of the doses of other sedatives will be preferred over the α-2 agonist treatment. In case of insufficient sedation despite maximal doses of α-2 agonist, other sedatives (choosen by the attending physician) will administered and titrated according to the scales for pain and sedation evaluation.

Drug: Clonidine

Dexmedetomidine

EXPERIMENTAL

Given that agitated delirium requires rapid medical intervention, α-2 agonist therapy (dexmedetomidine) will be administered as soon as possible. The α-2 agonist treatment that will be started will depend on the allocation of the previously randomized unit. The sedative and analgesic treatments will be administered and titrated according to the scales on the usual protocol of the service (evaluation of sedation (NICS) and analgesia (VAS, BPS, BPS-NI). In case of excessive sedation assessed by the scores and administration of combined treatments (α-2 agonist and other sedatives), the reduction of the doses of other sedatives will be preferred over the α-2 agonist treatment. In case of insufficient sedation despite maximal doses of α-2 agonist, other sedatives (choosen by the attending physician) will administered and titrated according to the scales for pain and sedation evaluation.

Drug: Dexmedetomidine

Interventions

Clonidine DRUG

The doses administered (clonidine 1500mg diluted in NaCl0.9% solution of 50 ml) ranged from 0.01μg/kg/min to 0.03μg/kg/min.

Also known as: Dexmedetomidine

Clonidine

Dexmedetomidine DRUG

The doses administered (dexmedetomidine 200mg diluted in NaCl0.9% 50ml) ranged from 0.4μg/kg/h and can be titrated up to 1.4μg/kg/h.

Dexmedetomidine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• present agitated delirium, confirmed by the CAM-ICU diagnostic scale
• require mechanical restraint or psychotropic / sedative

You may not qualify if:

• Acute neurological central or medullary problems (vascular, traumatic, infectious, tumoral causes)
• Severe hepatic insufficiency (Child C cirrhosis)
• Severe renal insufficiency (creatinine clearance \<30ml / min) or renal replacement therapy
• Bradycardia \<60 / min
• nd or 3rd degree atrioventricular block (unless placed pacemaker)
• Hemodynamic instability (MAP \<60mmHg despite adequate vascular filling and vasopressor treatment).
• Pregnant woman or breastfeeding
• Use of α-2 agonist or antagonist agents within 24 hours of randomization
• Allergy known to one of the α-2 agonists used in the study
• Moribund patient (survival prognosis at limited 24h or therapeutic de-escalation envisaged)

Sponsors & Collaborators

• Erasme University Hospital: lead

Study Sites (3)

CUB Erasme Hospital ULB

Brussels, 1070, Belgium

RECRUITING

Civil hospital Marie Curie

Charleroi, Belgium

RECRUITING

Clinique Saint-Pierre

Ottignies, Belgium

RECRUITING

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MeSH Terms

Conditions

Delirium; Critical Illness

Interventions

Clonidine; Dexmedetomidine

Condition Hierarchy (Ancestors)

Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders; Disease Attributes; Pathologic Processes

Intervention Hierarchy (Ancestors)

Imidazolines; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Creteur Jacques, MD PhD

  CUB Erasme Hospital ULB

  STUDY DIRECTOR

Central Study Contacts

Lheureux Olivier, MD

CONTACT

003225558330; olivier.lheureux@erasme.ulb.ac.be

Amédée Ego, MD

CONTACT

003225555705; amedee.ego@erasme.ulb.ac.be

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: February 10, 2021
• First Posted: February 17, 2021
• Study Start: February 1, 2021
• Primary Completion: February 28, 2022
• Study Completion: February 28, 2023
• Last Updated: February 17, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

BE (3)