E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of delirium in critically ill adult patients in intensive care unit. |
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E.1.1.1 | Medical condition in easily understood language |
Treatment of psychosis related to critical illness in adult patients admitted to intensive care unit |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess benefits and harms of haloperidol in adult, critically ill patients with delirium in the ICU. The primary objective is to determine, if haloperidol treatment in ICU patients with delirium will increase the number of days alive out of the hospital within 90 days. This primary objective includes 90 days mortality and length of hospital stay within 90 days after randomisation. |
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E.2.2 | Secondary objectives of the trial |
To investigate if haloperidol as compared with placebo in ICU patients with delirium will change the: - Number of days alive without delirium or coma in the ICU - Number of patients with one or more adverse reactions and/or the total number of adverse reactions to haloperidol compared with placebo. - Number of patients needing one or more doses of escape medicine and or the dosages of escape medicine per patient in the haloperidol Group compared with the placebo group - Number of days alive without mechanical ventilation in the 90-day trial period - One-year mortality after inclusion - Measurement of cognitive function one year after inclusion on selected trial sites. - A health economic analysis will be performed. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Acute admission to the ICU AND - Age ≥ 18 years AND - Diagnosed delirium with a validated screening tool as either CAM-ICU or ICDSC.
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E.4 | Principal exclusion criteria |
- Contraindications to haloperidol - Habitual treatment with any antipsychotic medication - Permanently incompetent (e.g. dementia, mental retardation) - Delirium assessment non-applicable (coma or language barriers) - Withdrawal from active therapy or brain death - Fertile women (women < 50 years) with positive urine human chorionic gonadotropin (hCG) or plasma-hCG - Consent according to national regulations not obtainable - Patients under coercive measures by regulatory authorities - Patients with alcohol-induced delirium (delirium tremens)
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E.5 End points |
E.5.1 | Primary end point(s) |
Days alive out of the hospital within 90 days post-randomisation |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
90 days post-randomisation |
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E.5.2 | Secondary end point(s) |
1. Number of days alive without delirium and coma in the ICU 2. Number of patients with one or more serious adverse reactions to haloperidol and total number of serious adverse reactions to haloperidol 3. Number of patients needing one or more doses of escape medicines and number of days with escape medicines per patient 4. Number of days alive without mechanical ventilation in the 90-day period 5. 1-year mortality post-randomisation 6. EQ-5D-5L and EQ-VAS one year after randomisation. Patients who have died will be assigned the lowest possible EQ-5D-5L and EQ-VAS score. 7. Cognitive function 1-year after randomisation as assessed using RBANS score at selected sites. 8. A health economic analysis will be performed. The analytic details will be based on the result of the trial and specified (cost-effectiveness vs. cost-minimisation analyses). Outcomes will be one-year mortality and Quality adjusted Life Years (QALYs). The latter will be conducted on the basis of Eq-5D-5L. The inclusion of QALYs generates a cost-utility analysis.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Endpoint number 1-4: 90 days post-randomisation Endpoint number 5-8: 1 year post-randomisation |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 20 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Denmark |
Finland |
United Kingdom |
Spain |
Italy |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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1 year post-randomisation of the last included patient in the trial |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |