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

NCT03317067 | Completed Phase 3 Results

• 2 other identifiers: CHU- 3562017-000731-14
• Study Type: interventional
• Target: 168
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Delirium; Agitation

Keywords

Dexmdetomidine; Haloperidol; Delirium; Productive Delirium; Agitation; Intubation; Ventilatory free days; Sedation; ICU patients; Mechanical Ventilation

Outcome Measures

Primary Outcomes (3)

• Duration of Agitation (in Hours), Defined by a RASS ≥ +1

  at day 1

• Duration of Delirium (in Days), Defined by a Positive CAM-ICU

  Day 30

• Requirement of Intubation

  requirement of intubation to control delirium with deep sedation and mechanical ventilation

  at day 1

Secondary Outcomes (6)

• Length of ICU Stay (in Days)

  day 30

• Number of Ventilator Free Days

  at day 30

• Adverse Effects Such as the Occurence of Pneumonia (Following the ATS Definitions) and/or Septicemia

  at day 30

• Occurrence of Hypotension Requiring Any Vasopressor Administration and / or Tachycardia

  at day 30

• All-cause Mortality

  at day 30

Study Arms (2)

dexmedetomidine

EXPERIMENTAL

Patients in the Dexmedetomidine (interventional) group will be treated with a continuous infusion of dexmedetomidine in case of agitated delirium.

Drug: Dexmedetomidine

Normal Saline (NaCl 0.9%)

PLACEBO COMPARATOR

Patients in the Normal Saline (control) group will be treated with a continuous infusion of normal saline in case of agitated delirium.

Other: Placebo

Interventions

Dexmedetomidine DRUG

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

dexmedetomidine

Placebo OTHER

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

Normal Saline (NaCl 0.9%)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• Age \<18 years
• 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

Sponsors & Collaborators

• University Hospital, Clermont-Ferrand: lead

Study Sites (1)

CHU Clermont-Ferrand

Clermont-Ferrand, 63003, France

Location

Related Publications (2)

• Godet T, Louis C, Rieu B, De Jong A, Couhault P, Pradel G, Tete H, Bourguignon N, Borao L, Jabaudon M, Futier E, Jaber S, Pereira B, Chanques G, Constantin JM; 4D study group. Dexmedetomidine for treatment of hyperactive delirium in non-intubated ICU patients: the 4D randomized clinical trial. Intensive Care Med. 2025 Dec;51(12):2305-2317. doi: 10.1007/s00134-025-08135-1. Epub 2025 Oct 29.

  PMID: 41160116 RESULT

• Louis C, Godet T, Chanques G, Bourguignon N, Morand D, Pereira B, Constantin JM; AZUREA network. Effects of dexmedetomidine on delirium duration of non-intubated ICU patients (4D trial): study protocol for a randomized trial. Trials. 2018 Jun 4;19(1):307. doi: 10.1186/s13063-018-2656-x.

  PMID: 29866205 DERIVED

MeSH Terms

Conditions

Delirium; Psychomotor Agitation

Interventions

Dexmedetomidine

Condition Hierarchy (Ancestors)

Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders; Dyskinesias; Psychomotor Disorders; Aberrant Motor Behavior in Dementia; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Prof. Thomas GODET
• Organization: CHU de Clermont-Ferrand

tgodet@chu-clermontferrand.de

+33 473751590

Study Officials

• Thomas GODET

  University Hospital, Clermont-Ferrand

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: double blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 9, 2017
• First Posted: October 23, 2017
• Study Start: December 21, 2017
• Primary Completion: May 21, 2021
• Study Completion: February 23, 2023
• Last Updated: May 13, 2026
• Results First Posted: May 13, 2026

Record last verified: 2023-02

Locations

FR (1)