E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute ischaemic stroke |
Ictus Isquémico agudo |
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E.1.1.1 | Medical condition in easily understood language |
Acute ischaemic stroke |
Ictus Isquémico agudo |
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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 investigate if: - Compared with standard dose i.v. rtPA, low-dose rtPA is at least as effective (not inferior) on the major clinical outcome of death or disability at 3 months (i.e. corresponding null hypothesis is that low-dose is inferior to standard dose rtPA); - Compared with standard guideline-based BP management, early intensive BP lowering is superior in reducing the risk of the major clinical outcome of death or disability at 3 months (i.e. corresponding null hypothesis is that there is no difference in treatments on this outcome). |
Investigar si: - En comparación con la dosis estándar de la administración i.v. rtPA, una dosis baja de rtPA es al menos tan eficaz (no inferior) en el resultado clínico importante de muerte o discapacidad a los 3 meses - En comparación con la administración estándar de la PA según las guías, la disminución temprana intensiva de la PA es superior en la reducción del riesgo de muerte o discapacidad a los 3 meses. |
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E.2.2 | Secondary objectives of the trial |
To investigate if: - Compared with standard dose i.v. rtPA, low-dose rtPA reduces the risk of sICH - Compared with standard guideline-based BP management, early intensive BP lowering after thrombolysis with rtPA reduces the risk of any ICH (i.e. corresponding null hypothesis is that there is no difference in the rate of any ICH between groups of differing intensities of BP lowering). |
Investigar si: - En comparación con la dosis estándar de la administración i.v. rtPA, una dosis baja de rtPA reduce el riesgo de ICH - En comparación con la administración estándar de la PA según las guías, temprana intensiva disminución de la PA después de la trombolisis con rtPA reduce el riesgo de cualquier ICH. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- General criteria for use of thrombolytic treatment with rtPA. (a) Adult (age >18 years) (b) A clinical diagnosis of acute ischaemic stroke confirmed by brain imaging (c) Able to receive treatment within 4.5 hours after the definite time of onset of symptoms (d) Have a systolic BP ?185 mmHg (i.e. the guideline recommended level of eligibility for rtPA; patients with higher BP levels at presentation can still be included provided the BP is reduced to the entry level prior to commencement of the randomised treatment) (e) Provide informed consent (or via an appropriate proxy, according to local requirements) |
- Criterios generales para el uso del tratamiento trombolítico con rtPA. (a) adulto (edad> 18 años) (b) Un diagnóstico clínico de accidente cerebrovascular isquémico agudo confirmado por imágenes del cerebro (c) Capaz de recibir tratamiento dentro de 4,5 horas después del tiempo definido de inicio de los síntomas (d) Tener una presión arterial sistólica de 185 mmHg (e) Proporcionar el consentimiento informado |
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E.4 | Principal exclusion criteria |
(a) Unlikely to potentially benefit from the therapy (e.g. advanced dementia), or a very high likelihood of death within 24 hours of stroke onset. (b) Other medical illness that interferes with outcome assessments and follow-up [known significant pre-stroke disability (mRS scores 2-5)]. (c) Specific contraindications to rtPA (Actilyse) or any of the blood pressure agents to be used. (d) Participation in another clinical trial involving evaluation of pharmacological agents (e) Need for following concomitant medication, including phosphodiesterase inhibitors and monoamine oxidase inhibitors. |
(a) Improbabilidad de beneficiarse de la terapia (por ejemplo, demencia avanzada), o una muy alta probabilidad de muerte dentro de las 24 horas de inicio del accidente cerebrovascular. (b) Otra enfermedad médica que interfiera con la evaluación de los resultados y del seguimiento [MRS puntajes 2-5]. (c) las contraindicaciones específicas a rtPA (Actilyse) o cualquiera de los agentes de presión arterial que se utilizarán. (d) Participación en otro ensayo clínico que incluya la evaluación de agentes farmacológicos (e) Necesidad de medicación concomitante, incluidos los inhibidores de la fosfodiesterasa e inhibidores de la monoamino oxidasa. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary outcome is the combined endpoint of death and disability as defined by the dichotomised 0-1 versus 2-6 cut-point on the modified Rankin Scale [mRS] at 3 months. |
El variable principal es la combinación de muerte y discapacidad según la definición de punto de corte de 0-1 versus 2-6 en la escala de Rankin modificada [MRS] a los 3 meses. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary outcomes are: (a) symptomatic ICH based on NINDS criteria of brain imaging (or necropsy) confirmed ICH with 1 points deterioration in NIHSS score or death within 36 hours from baseline; (b) symptomatic ICH, defined by SITS-MOST criteria, as large (type II) parenchymal ICH with 4 points decline in NIHSS score or death within 36 hours from baseline; and (c) ICH of any type in brain imaging 7 days of treatment; (d) death or disability by the alternative, but less widely used, shift analysis of scores on the mRS, (e) death, (f) disability, (g) neurological deterioration 4 points decline in NIHSS score over 72 hours, (h) HRQoL by the EuroQoL, (i) admission to residential care, and (j) health service use for calculation of resources and costs. |
Las variables secundarias son: (a) ICH sintomática sobre la base de criterios NINDS de imagen cerebral (o la necropsia) con 1 punto de deterioro en la puntuación NIHSS o muerte dentro de las 36 horas a partir del estado basal; (b) ICH sintomática, definida por los criterios SITS-MOST, como ICH del parénquima grande (tipo II) con 4 puntos de descenso en la puntuación NIHSS o muerte dentro de las 36 horas a partir del estado basal; y (c) ICH de cualquier tipo en imagen cerebral de 7 días de tratamiento; (d) muerte o discapacidad por análisis de la puntuación mRS (e) muerte, (f) discapacidad, (g) deterioro neurológico de 4 puntos en la puntuación NIHSS durante 72 horas, (h) CVRS por el EuroQoL, (i) admisión a la atención residencial, y (j) uso de servicios de salud para el cálculo de los recursos y los costes. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Especified in each end point |
Especificado en cada variable |
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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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Prospectivo aleatorizado abierto, variable ciega |
Prospective randomized open, blinded end-point (PROBE) |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
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 |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
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 | 5 |