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. |
Tratamiento del Delirium para pacientes críticos de la Unidad de Cuidados Intensivos |
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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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Tratamiento de la psicosis relacionada con enfermedades críticas en pacientes adultos ingresados en la unidad de cuidados intensivos |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000702 |
E.1.2 | Term | Acute delirium |
E.1.2 | System Organ Class | 100000004873 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10013758 |
E.1.2 | Term | Drug-induced delirium |
E.1.2 | System Organ Class | 100000004873 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10042275 |
E.1.2 | Term | Subacute delirium |
E.1.2 | System Organ Class | 100000004873 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012220 |
E.1.2 | Term | Delirium due to a general medical condition |
E.1.2 | System Organ Class | 100000004873 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012226 |
E.1.2 | Term | Delirium, cause unknown |
E.1.2 | System Organ Class | 100000004873 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10050233 |
E.1.2 | Term | Delirium on emergence |
E.1.2 | System Organ Class | 100000004863 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10071313 |
E.1.2 | Term | Hypoactive delirium |
E.1.2 | System Organ Class | 100000004873 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10071314 |
E.1.2 | Term | Hyperactive delirium |
E.1.2 | System Organ Class | 100000004873 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10071315 |
E.1.2 | Term | Mixed delirium |
E.1.2 | System Organ Class | 100000004873 |
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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. |
Evaluar los beneficios y los daños del haloperidol en pacientes adultos con enfermedades graves con delirio en la UCI. El objetivo principal es determinar si el tratamiento con haloperidol en pacientes de la UCI con delirio aumentará el número de días vivos fuera del hospital dentro de los 90 días. Este objetivo primario incluye 90 días de mortalidad y la duración de la estancia hospitalaria dentro de los 90 días posteriores a la asignación al azar. |
|
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. |
Para investigar si el haloperidol en comparación con el placebo en pacientes de UCI con delirio cambiará:
- Número de días de vida sin delirio o coma en la UCI
- Número de pacientes con una o más reacciones adversas y / o el número total de reacciones adversas al haloperidol en comparación con placebo.
- Número de pacientes que necesitan una o más dosis de medicamento de escape y / o las dosis de medicamento de escape por paciente en el grupo de haloperidol en comparación con el grupo de placebo
- Número de días de vida sin ventilación mecánica en el período de prueba de 90 días.
- Mortalidad a un año después de la inclusión.
- Medición de la función cognitiva un año después de la inclusión en sitios de prueba seleccionados.
- Se realizará un análisis económico de salud. |
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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. |
- Ingresados Agudos en la UCI (Unidad de Cuidados Intensivos)
- Edad ≥ 18 años
- Delirium diagnosticado con una escala validada como CAM-ICU o 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) |
- Contraindicaciones de Haloperidol
- Tratamiento habitual con cualquier mediación antipsicótica
- Incompetencia permanente (demencia, retraso mental)
- Evaluación del delirio no aplicable (coma o barreras del idioma)
- Retirada por terapia activa o muerte cerebral
- Mujeres fértiles (mujeres <50 años) con gonadotropina coriónica humana (hCG) o plasma-hCG en orina positivas.
- No obtención del Consentimiento de acuerdo con la normativa nacional
- Pacientes bajo medidas coercitivas por autoridades reguladoras
- Pacientes con delirio inducido por alcohol (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 |
Días vivos fuera del hospital dentro de los 90 días posteriores a la aleatorización |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
90 days post-randomisation |
90 días después de randomización |
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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. Usage of escape medicine and dosage of escape medicine 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. |
1. Número de días de vida sin delirio y coma en la UCI
2. Número de pacientes con una o más reacciones adversas graves al haloperidol y número total de reacciones adversas graves al haloperidol
3. Uso de medicamento de escape y dosis de medicamento de escape por paciente
4. Número de días vivos sin ventilación mecánica en el período de 90 días.
5. Mortalidad al año después de la aleatorización
6. EQ-5D-5L y EQ-VAS un año después de la asignación al azar. A los pacientes que hayan fallecido se les asignará el puntaje EQ-5D-5L y EQ-VAS más bajo posible.
7. Función cognitiva 1 año después de la asignación al azar, evaluada mediante la puntuación RBANS en los sitios seleccionados.
8. Se realizará un análisis económico de salud. Los detalles analíticos se basarán en el resultado del ensayo y se especificarán (análisis de costo-efectividad versus análisis de minimización de costos). Los resultados serán la mortalidad a un año y los años de vida ajustados por calidad (AVAC). Este último se llevará a cabo sobre la base de Eq-5D-5L. La inclusión de AVAC genera un análisis de costo-utilidad. |
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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 |
Punto final número 1-4: 90 días después de la aleatorización
Punto final número 5-8: 1 año después de la asignación al azar |
|
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 |
France |
Italy |
Norway |
Spain |
Sweden |
United Kingdom |
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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 |
|
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 |