DeliriumPhase 34DNCT03317067
Effects of Dexmedetomidine on Delirium Duration of Non-intubated ICU Patients (4D Trial)
A Phase 3 study testing Dexmedetomidine in people with Delirium and Agitation, run by University Hospital, Clermont-Ferrand at 1 site in France.
Trial summary
The primary purpose of the study is to evaluate whether dexmedetomidine is effective in treating agitated delirium of non-intubated ICI patients Read more about this study
- Who is it for?
- Ages 18 years and older
- 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
- 168 participants
- Where
- 1 siteFrance
- Study dates
- 21 Dec 2017to 23 Feb 2023
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- • 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
Show all 9Show fewer
- CAM-ICU positive AND a RASS > +1
- Non-intubated or extubated (> 24h)
- No contraindication of dexmedetomidine or haloperidol uses
Who cannot join
- • 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
Trial locations and contacts
1 site in 1 country.
About this study
The primary purpose of the study is to evaluate whether dexmedetomidine is effective in treating agitated delirium of non-intubated ICI patients
Read the detailed 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.
- Being tested
- Dexmedetomidine, Placebo
- Keywords
- Dexmdetomidine, Haloperidol, Delirium, Productive Delirium, Agitation, Intubation, Ventilatory free days, Sedation, ICU patients, Mechanical Ventilation
- Medical subject headings
- Delirium, Psychomotor Agitation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexmedetomidineDrug
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
PlaceboOther
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
| Study group | Role | What they receive |
|---|---|---|
| dexmedetomidine | Experimental | Patients in the Dexmedetomidine (interventional) group will be treated with a continuous infusion of dexmedetomidine in case of agitated delirium. Receives: 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. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Duration of Agitation (in Hours), Defined by a RASS ≥ +1
Measured: at day 1
Duration of Delirium (in Days), Defined by a Positive CAM-ICU
Measured: Day 30
Requirement of Intubation
requirement of intubation to control delirium with deep sedation and mechanical ventilation
Measured: at day 1
Secondary outcomes (6)
Length of ICU Stay (in Days)
Measured: day 30
Number of Ventilator Free Days
Measured: at day 30
Adverse Effects Such as the Occurence of Pneumonia (Following the ATS Definitions) and/or Septicemia
Measured: at day 30
Occurrence of Hypotension Requiring Any Vasopressor Administration and / or Tachycardia
Measured: at day 30
All-cause Mortality
Measured: at day 30
All-cause Mortality
Measured: at day 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2017
- Study start21 Dec 2017
- Primary completion21 May 2021
- Study completion23 Feb 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for DeliriumStudies of the same condition, open and under way.
- More trials run by University Hospital, Clermont-FerrandThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 168 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Clermont-Ferrand
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Thomas GODET, Principal investigator, University Hospital, Clermont-Ferrand
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03317067
- Sponsor's protocol ID
- CHU- 356
- Other IDs
- 2017-000731-14, 2017
- Acronym
- 4D
- Status last verified
- Feb 2023
- First submitted
- 9 Oct 2017
- Last updated
- 13 May 2026
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 41160116Louis 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.
PubMed 29866205
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Dexmedetomidine on Delirium Duration of Non-intubated ICU Patients (4D Trial)
- ClinicalTrials.gov ID
- NCT03317067
- Acronym / sponsor ID
- 4D / CHU- 356
- Keywords
- Dexmdetomidine, Haloperidol, Delirium, Productive Delirium, Agitation, Intubation, Ventilatory free days, Sedation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 168 participants (actual)
- Lead sponsor
- University Hospital, Clermont-FerrandUniversity, hospital or other
- Study start
- 21 Dec 2017 (actual)
- Primary completion
- 21 May 2021 (actual)
- Study completion
- 23 Feb 2023 (actual)
- First posted
- 23 Oct 2017 (actual)
- Results
- Posted 13 May 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary purpose of the study is to evaluate whether dexmedetomidine is effective in treating agitated delirium of non-intubated ICI patients
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| dexmedetomidine | Experimental | Drug: DexmedetomidinePatients in the Dexmedetomidine (interventional) group will be treated with a continuous infusion of dexmedetomidine in case of agitated delirium. |
| Normal Saline (NaCl 0.9%) | Placebo comparator | Other: PlaceboPatients in the Normal Saline (control) group will be treated with a continuous infusion of normal saline in case of agitated delirium. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- • Age > 18 years
Key exclusion criteria (7 listed)
- • Age <18 years
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 |
|---|---|---|
| DexmedetomidineThe 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 | Drug | dexmedetomidine |
| PlaceboThe 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 | Normal Saline (NaCl 0.9%) |
Primary outcome
Duration of Agitation (in Hours), Defined by a RASS ≥ +1
Time frame: at day 1
Duration of Delirium (in Days), Defined by a Positive CAM-ICU
Time frame: Day 30
Requirement of Intubation
Time frame: at day 1
requirement of intubation to control delirium with deep sedation and mechanical ventilation
6 secondary outcomes
Length of ICU Stay (in Days)
Time frame: day 30
Number of Ventilator Free Days
Time frame: at day 30
Adverse Effects Such as the Occurence of Pneumonia (Following the ATS Definitions) and/or Septicemia
Time frame: at day 30
Occurrence of Hypotension Requiring Any Vasopressor Administration and / or Tachycardia
Time frame: at day 30
All-cause Mortality
Time frame: at day 30
All-cause Mortality
Time frame: at day 7
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 41160116Godet 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.
- Derived from this study: PubMed 29866205Louis 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.
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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.
Thomas GODET principal investigator
University Hospital, Clermont-Ferrand
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Dexmedetomidine in people with Delirium and Agitation, run by University Hospital, Clermont-Ferrand at 1 site in France.
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 9 inclusion and 7 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 13 May 2026. 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 France. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 May 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Duration of Agitation (in Hours), Defined by a RASS ≥ +1 (time frame: at day 1). The study lists 3 primary outcomes in all. 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 NCT03317067, which also lists 2 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 13 May 2026.