Please select the eligibility criteria that correspond to the clinical trial below.
Title: Efficacy of Haloperidol to Decrease the Burden of Delirium in Adult Critically Ill Patients (EuRIDICE): a Prospective Randomised Multi-center Double-blind Placebo-controlled Clinical Trial
Brief Summary: The EuRIDICE trial will study whether haloperidol as a first line treatment for ICU delirium reduces delirium duration (and severity). Adverse outcomes typically associated with delirium will also be studied and include long term cognition, functional outcome and quality of life. Further, patient and family experiences and cost-effectiveness will be assessed. Finally, safety concerns associated with the use of haloperidol in this vulnerable population will be studied.


Options:
A: 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:

Eligibility

Inclusion criteria for eligibility

1. Age ≥ 18 years
2. Admitted to ICU.

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 or other psychotic disorder
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, or is expected to leave the ICU 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
B: Inclusion Criteria:

* Participated in the ALTA, EDEN, OMEGA, or SAILS study
* Survived until hospital discharge

Exclusion Criteria:

* Does not understand or speak English
* Has no fixed address
* Pre-existing cognitive impairment that prevents completion of the study assessments
C: Inclusion Criteria:

Patients will be eligible for the study if, in the opinion of the treating clinician, they continue to require mechanical ventilation only because their degree of agitation requires such a high dose of sedative medication (midazolam or propofol, the only commonly used specific sedatives in our unit) that extubation is not possible, AND in the opinion of their treating intensivist their agitation is so severe as to make lessening their sedation unsafe.

These criteria will be objectively quantified as follows:

* they have required either mechanical restraint and/or anti-delirium or sedative medication in the 4 hours prior to seeking consent AND
* their Confusion Assessment Method for the ICU (CAM-ICU) test is positive for delirium in the 4 hours prior to seeking consent AND
* their Motor Activity Assessment Scale (MAAS) score is 5 or more in the 4 hours prior to seeking consent, confirming psychomotor agitation AND
* their SOFA score is less than or equal to 5 in the 4 hours prior to seeking consent, predicting a mortality or around 5%.

Exclusion Criteria:

* Age less than 18 years old
* Pregnancy or breastfeeding
* Advanced dementia (in the premorbid state requiring professional nursing care)
* Open or closed head injury
* Death is deemed imminent and inevitable
* The patient has previously been enrolled in the DahLIA study
* Patients who could not be extubated, or who would be intubated within the following 48 hours, even if delirium or agitation were corrected. This will include:

  * Patients receiving high dose opioid for analgesia (not sedation) ( \> 40 mg/morphine/day)
  * Patients shortly to return to the operating theatre
  * Patients undergoing repeated invasive procedures, in whom it is desirable to maintain deep sedation
  * Patients likely to require ongoing airway protection or control, or ventilatory support (for example, spinal patients with an inadequate vital capacity)
* Known allergy to haloperidol or alpha 2 agonists
D: Inclusion Criteria:

* Male or female adult patients admitted to the medical and surgical ICU for critical illnesses requiring mechanical ventilation with expectation of being mechanically ventilated for greater than 24 hours

Exclusion Criteria:

* Subjects who are less than 18 years of age
* Subjects who are pregnant (a pregnancy test will be performed on all women of child bearing age)
* Inability to obtain informed consent from the patient or his/her surrogate
* Subjects in the ICU due to a lack of beds elsewhere in the hospital, triage issues, or withdrawal of care decisions rather than severity of illness
* Subjects admitted with alcohol or drug overdoses, suicide attempts, or alcohol/delirium tremens
* Subjects who are physiologically benzodiazepine dependent, and at risk for withdrawal syndromes
* Subjects with chronic pain syndromes on maintenance narcotics
* Subjects treated within the last 30 days with a drug or device that has not received regulatory approval as of study entry
* Subjects with a psychiatric history for which they are on neuroleptic treatment
* Subjects with documented moderate to severe dementia
* Subjects with anoxic brain injuries, strokes, neurotrauma, or neuromuscular disorders such as myasthenia gravis or Guillain Barre syndrome
* Medical team following patient unwilling to use the sedation regimens
* Subjects whose family and/or physician have not committed to aggressive support for 72 hours or who are likely to withdraw within 72 hours
* Subjects who are moribund and not expected to survive 24 hours
* Subjects not expected to survive hospital discharge due to preexisting uncorrectable medical condition
* Documented allergy to study medications
* Subjects who have either Child-Pugh Class B or C cirrhosis
* Subjects with active coronary artery disease at time of screening as defined by any recent evidence of ischemia, documented myocardial infarction, or coronary intervention within the past 6 months.
* Subjects with advanced heart block at time of screening

Answer: A