Delirium MedDRA version: 21.0 Level: LLT Classification code 10012224 Term: Delirium toxic System Organ Class: 100000004873 MedDRA version: 21.1 Level: LLT Classification code 10000702 Term: Acute delirium System Organ Class: 100000004873 MedDRA version: 21.1 Level: LLT Classification code 10042275 Term: Subacute delirium System Organ Class: 100000004873 MedDRA version: 21.0 Level: LLT Classification code 10012220 Term: Delirium due to a general medical condition System Organ Class: 10000000
Conditions
Interventions
Trade Name: Haloperidol
Pharmaceutical Form: Solution for infusion
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use
Sponsors
Erasmus Medical Center Rotterdam
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria for eligibility: 1. Age = 18 years 2. Admitted to one of six participating ICUs of the EuRIDICE trial. Inclusion criteria for randomisation: 1. Delirium, as assessed with the Intensive Care Delirium Screening Checklist – ICDSC: =4 or Confusion Assessment Method for the ICU – CAM-ICU: positive). NB Delirium can occur in the course of ICU admission or be present at admission. 2. Written Informed Consent is obtained from patient or legal representative 3. Complies with inclusion criteria but NOT exclusion criteria for eligibility Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 349 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 393
Exclusion criteria
Exclusion criteria: Exclusion criteria for eligibility 1. Admitted to ICU with a neurological diagnosis (such as acute stroke, traumatic brain injury, intracranial malignancy, anoxic coma). Previous non-acute stroke or other previous neurological condition without cognitive deterioration is not an exclusion criterion. 2. Pregnancy (to be excluded by pregnancy test in women of child baring age) 3. History of ventricular arrhythmia including “torsade de pointes” (TdP) 4. Known allergy to haloperidol 5. History of dementia or an Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) score = 4 6. History of malignant neuroleptic syndrome or parkinsonism (either Parkinson’s disease or another hypokinetic rigid syndrome) 7. Schizophrenia 8. Inability to conduct valid delirium screening assessment (e.g. coma, deaf, blind) or inability to speak Dutch 9. The patient is expected to die within 24 hours, or is expected to leave the ICU within 24 hours after evaluation (may be reassessed daily) Exclusion criteria for randomisation: 1. Prolonged QT-interval (QTc > 500ms) 2. (recent) “torsade de pointes” (TdP) 3. (recent) malignant neuroleptic syndrome or parkinsonism 4. Evidence of acute alcohol (or substance) withdrawal requiring pharmacological intervention (e.g. benzodiazepines or alfa-2 agonist) to treat 5. IQCODE not assessed 6. The patient is expected to die within 24 hours. 7. No (previously) signed informed consent by patient or representative 8. Current participation in another intervention trial that is evaluating a medication, device or behavioural intervention
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of haloperidol to resolve delirium in adult critically ill patients and thereby render the patient awake and non-delirious.;Secondary Objective: To study the efficacy of haloperidol to reduce ICU-delirium associated short- and long-term burdens (up to one-year), consisting of: 1) mortality; 2) cognitive and functional impairment; 3) patient- and family experiences and psychological sequelae during and after ICU stay; 4) safety concerns associated with haloperidol use.;Primary end point(s): Delirium- and coma free days at ICU ;Timepoint(s) of evaluation of this end point: Up to 14 days after randomisation | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: During ICU admission, at discharge from hospital, after 28 days, 1 month, 3 months, 6 months and 12 months.;Secondary end point(s): • Time from randomisation to resolution of delirium into a wakeful, non-delirious state. • Cognitive outcomes in ICU survivors at 3 and 12 months after ICU admission (assessment by trained research nurses or MSc students neuropsychology is feasible) with a brief cognitive assessment battery of validated and repeatable measures of general cognition, memory, language, processing speed, attention and executive functioning and mood (Montreal Cognitive Assessment [MOCA], Rey Auditory Verbal Learning Test, Semantic fluency, Digit Span [WAIS-IV], Trailmaking tests A and B, Boston naming Test [short version], Hospital Anxiety and Depression Scale [HADS]). • Functional outcomes and quality of life in survivors at 3 and 12 months after admission (Short Form-36 [SF-36]). • Mortality rate at 28 days and one year after randomisation. • Time to “readiness for discharge from the ICU”, as is being recorded routinely by all participating hospitals by the treating physicians on a daily basis, as an alternative to length-of-ICU stay which may be determined by other factors (e.g. capacity at the ward) than clinical condition. • Adverse drug associated events (prolonged QTc by EKG, muscle rigidity and other associated movements disorders [Simpson Angus Scale] and ventricular arrhythmia’s including torsade de pointes). • Patient and family-member well-being and experiences associated with delirium during and after ICU stay, assessed after hospital discharge and at 3 months after randomisation. We have chosen the most appropriate tool after consultation of our patient perspective representatives and the Steering Committee associated with this trial. The tools for this category of secondary outcomes are added to Appendix 2 (including a Table with overview of timing of assessments), and include the ICU Memory Tool | — |
Countries
Netherlands
Contacts
Public ContactMathieu van der Jagt
Erasmus Medical Center Rotterdam
Outcome results
None listed