Effects of Dexmedetomidine on Delirium Duration of Non-intubated ICU Patients (4D Trial)

Delirium Clinical Trial

— 4D  

Official title:

Effects of Dexmedetomidine on Delirium Duration of Non-intubated ICU Patients (4D Trial)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03317067
• Other study ID #: CHU- 356
• Secondary ID: 2017-000731-14
• Status: Completed
• Phase: Phase 3
• Start date: December 21, 2017
• Est. completion date: February 23, 2023

Study information

• Verified date: February 2023
• Source: University Hospital, Clermont-Ferrand
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary purpose of the study is to evaluate whether dexmedetomidine is effective in treating agitated delirium of non-intubated ICI patients

Description:

Delirium during intensive care unit (ICU) stay is frequent and associated with significant morbidity, mortality and healthcare related costs. International guidelines suggest its prevention. However, curative treatment remains unclearly established. Despite a non-unequivocal literature, haloperidol is the first line recommended neuroleptic. Dexmedetomidine, an alpha2-adrenergic receptors agonist has shown its efficiency in the treatment of delirium in intubated patients but also in its prevention. Dexmedetomidine represents a widely used alternative to haloperidol. Only few studies have compared the efficacy of dexmedetomidine in non-intubated ICU patients as a first line curative treatment of delirium. Main objective of 4D trial is to demonstrate that dexmedetomidine decreases delirium duration compared to placebo.

The 4D trial is an investigator-initiated, prospective, multicenter, randomized, double-blinded, two-arm trial, randomizing 300 non-intubated ICU patients with diagnosis of agitated delirium to receive dexmedetomidine or placebo as a cure. The primary outcome measure is a composite of duration of agitation or delirium or the use of intubation with deep sedation and mechanical ventilation. Secondary outcomes include mortalities at 7 and 28 days, ICU length of stay and occurrence of adverse effects. The sample size will allow the detection of a 50% decrease of agitation duration (120 minutes), of an absolute reduction of delirium duration (1 day) and of a 50% relative decrease of intubation and mechanical ventilation, with a type 1 error rate of 1.8 % (error risk inflation due to components of composite) and power of 90 %, assuming a 15 % incidence of intubation and mechanical ventilation requirements, an agitation duration of 240 minutes and a delirium duration of 3 days. One hundred and 10 patients by group will be needed. A intermediate analysis is scheduled and requires the inclusion of 150 patients in each group.

The 4D trial may provide important data on the safety of commonly used sedative dexmedetomidine and could have a significant impact on future treatment of non-intubated ICU patients presenting with agitated delirium.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 151
• Est. completion date: February 23, 2023
• Est. primary completion date: May 21, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• • Age > 18 years

• Patient hospitalized in an ICU

• Presenting a productive delirium according to the following criteria:

• acute onset (<2h) and fluctuating course during the same day

• alteration of cognitive functions: disorganization of thought (delirium of persecution, inability to reason logically), abnormal perceptions (hallucinations), memory impairments, temporal disorientation, non- or misrecognitions, difficulties in naming objects or writing)

• in whom a simple cropping and non-medicated therapeutics are not sufficient to allow symptoms' resolution for few hours

• CAM-ICU positive AND a RASS > +1

• Non-intubated or extubated (> 24h)

• No contraindication of dexmedetomidine or haloperidol uses

Exclusion Criteria:

• • Age <18 years

• Administration of dexmedetomidine and/or clonidine during the 72 hours before inclusion

• Contraindication to the use of Dexmedetomidine, clonidine or haloperidol (history of allergy, Parkinson's disease, oro-pharyngeal dysfunction, arterial hypotension or bradycardia, QTc interval prolongation, and hepatic or renal dysfunction), as mentioned in the Summaries of Product Characteristics

• Neuropsychiatric pathology judged by the investigator as a potential source of bias (in particular: active drug addiction, psychosis...)

• Parturient or breast-feeding woman

• Protected major (guardianship)

• Patient's or relative's refusal to participate

Related Conditions & MeSH terms

• Agitation
• Delirium
• Psychomotor Agitation

Intervention

Drug:
• Dexmedetomidine
The 4D trial is an investigator-initiated, prospective, multicenter, randomized, double-blinded, two-arm trial, randomizing 300 non-intubated ICU patients with diagnosis of agitated delirium to receive dexmedetomidine or placebo as a cure

Other:
• Placebo
The 4D trial is an investigator-initiated, prospective, multicenter, randomized, double-blinded, two-arm trial, randomizing 300 non-intubated ICU patients with diagnosis of agitated delirium to receive dexmedetomidine or placebo as a cure

Locations

Country	Name	City	State
France	CHU Clermont-Ferrand	Clermont-Ferrand

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Clermont-Ferrand

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	duration of agitation (in hours), defined by a RASS = +1		at day 1
Primary	duration of delirium (in days), defined by a positive CAM-ICU		at day 1
Primary	delay (in hours) between inclusion and intubation requirement to control delirium with deep sedation and mechanical ventilation	requirement of intubation to control delirium with deep sedation and mechanical ventilation	at day 1
Secondary	Length of ICU stay (in days)		at day 1
Secondary	Number of ventilator free days		at day 30
Secondary	Adverse effects such as the occurence of pneumonia (following the ATS definitions) and/or septicemia		at day 30
Secondary	Duration of mechanical restraint prescribed and carried out		at day 30
Secondary	Occurrence of tachycardia		at day 30
Secondary	Occurrence of hypotension requiring any vasopressor administration		at day 30
Secondary	All-cause mortality		at day 30
Secondary	All-cause mortality		at day 7