Clinical Trials Register

Summary
EudraCT Number:	2005-005763-28
Sponsor's Protocol Code Number:	PM-C-0225
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2006-07-07
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2005-005763-28

A.3

Full title of the trial

Estudio aleatorizado, doble ciego, en el que se comparan los efectos de un régimen de clopidogrel durante 3 meses en combinación con AAS durante el primer mes, frente a AAS en monoterapia, para el tratamiento agudo de pacientes con AIT o ictus menor.

Randomized, double-blind trial comparing the effects of a 3-month clopidogrel regimen, combined with ASA during the first month, versus ASA alone for the acute treatment of patients with TIA or minor stroke

A.3.2

Name or abbreviated title of the trial where available

CASTIA

A.4.1

Sponsor's protocol code number

PM-C-0225

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Sanofi-Aventis Groupe
B.1.3.4	Country	France
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Plavix
D.2.1.1.2	Name of the Marketing Authorisation holder	Sanofi Pharma Bristol-Myers Squibb SNC
D.2.1.2	Country which granted the Marketing Authorisation	Spain
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	clopidogrel
D.3.9.2	Current sponsor code	SR25990C
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	75
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Information not present in EudraCT
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Information not present in EudraCT
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Ácido acetilsalicílico
D.3.2	Product code	NA
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Ácido acetilsalicílico
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	75
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Information not present in EudraCT
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Information not present in EudraCT
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Information not present in EudraCT
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Ácido acetilsalicílico
D.3.2	Product code	NA
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Ácido acetilsalicílico
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	160 to 325
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Information not present in EudraCT
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Information not present in EudraCT
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

El tratamiento agudo de pacientes con AIT o ictus menor.

The acute treatment of patients with TIA or minor stroke

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	8.1
E.1.2	Level	HLT
E.1.2	Classification code	10008192

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Evaluar los efectos de un régimen de clopidogrel durante 3 meses, con dosis de carga de 300 mg seguida de 75 mg/día, en combinación con 75 mg/día de AAS durante el primer mes, frente a monoterapia con AAS 75 mg/día durante 3 meses, sobre la reducción de la aparición de nuevos episodios vasculares isquémicos (ictus isquémico clínico, nuevo infarto isquémico en RM cerebral, infarto de miocardio o muerte por causas vasculares) en pacientes con AIT agudo / ictus menor.

E.2.2

Secondary objectives of the trial

Evaluar por separado los efectos de dicha pauta de clopidogrel, en comparación con AAS en monoterapia, sobre la incidencia de:
-Nuevos episodios vasculares isquémicos clínicos (ictus isquémico / IM / muerte por causas vasculares) como variable combinada, e individualmente.
- Nuevo/s infarto/s cerebral/es detectados mediante RM.

Evaluar los cambios en la escala de Rankin modificada (continua) y el porcentaje de pacientes con una puntuación de 0-2 en la última visita de seguimiento.

Comparar la seguridad de ambas pautas terapéuticas expresada como:
-Hemorragia grave o moderada (definición GUSTO).
- Hemorragia cerebral.
- Mortalidad total.
- AA / AAG.

Comparar la eficacia y la seguridad según el episodio determinante (AIT vs. ictus).

Comparar la eficacia y la seguridad según el tiempo hasta la aleatorización,< 12 horas frente a ≥12 horas.

En un análisis posterior, evaluar el cambio en la puntuación de la NIHSS y la función cognitiva en los supervivientes.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

En los centros y pacientes que convengan en participar, se tomarán muestras de sangre en la visita basal para determinación de los siguientes parámetros:

hsCRP
IL6
Mieloperoxidasa (MPO)
LDL conjugadas con malondialdehido
LDL oxidada

E.3

Principal inclusion criteria

1) Hombres o mujeres ≥ 40 años.
2) AIT (≥ 10 minutos) o ictus isquémico agudo menor (NIHSS ≤ 3 en el momento de la aleatorización) que se pueda tratar con el medicamento en investigación antes de
transcurridas 24 horas del inicio de los síntomas.
3) Consentimiento informado firmado.
4) RM cerebral realizada antes de transcurridas 24 horas del inicio de los síntomas y previa a la aleatorización.

E.4

Principal exclusion criteria

Relacionados con las contraindicaciones al uso del clopidogrel y/o AAS:

1) Antecedentes de alergia a los derivados tienopiridínicos o al AAS.
2) Hipertensión no controlada grave pese al tratamiento en el momento de la aleatorización.
3) Antecedentes de trombocitopenia clínicamente significativa o persistente.
4) Antecedentes de neutropenia clínicamente significativa o persistente.
5) Mujeres en edad fértil que no utilicen un método anticonceptivo eficaz.
6) Mujeres en periodo de lactancia.
7) Otras contraindicaciones al uso de AAS (como insuficiencia renal o hepática grave, insuficiencia cardiaca grave, asma)

Relacionados con medicamento/s / tratamiento/s concomitante/s o previsto/s:
8) Necesidad absoluta de administrar de forma abierta clopidogrel, ticlopidina, antagonistas de los receptores GpIIb/IIIa, trombolíticos, heparinas o anticoagulantes
orales.
9) Uso de trombólisis dentro de las 24 horas anteriores a la aleatorización.
10) Tratamiento en la actualidad (última dosis administrada dentro de los 10 días anteriores a la aleatorización) con antagonistas de los receptores GpIIb/IIIa, heparinas o anticoagulantes orales.
11) Necesidad absoluta de administrar una dosis más alta de AAS (> 75 mg/día) o AAS + dipiridamol.
12) Tratamiento diario, tanto en la actualidad como previsto, con AINEs.
13) Revascularización prevista o probable (angioplastia o cirugía vascular) dentro de los próximos 3 meses (si están clínicamente indicadas, las pruebas de diagnóstico por imagen deben realizarse, antes de la aleatorización, siempre que sea posible).

Relacionados con las características del AIT / ictus:
14) Diagnóstico de hemorragia, malformación vascular, tumor, absceso u otra enfermedad cerebral no isquémica grave (como, por ejemplo, esclerosis múltiple, anomalía congénita mayor) en la RM cerebral basal.
15)Síntomas sensitivos puros, vértigo o mareos puros, o pérdida de visión pura sin indicios de infarto agudo en RM.
16) Puntuación modificada de Rankin > 2 en la aleatorización.
17) Puntuación en la escala de ictus NIHSS > 3 en la aleatorización.
18) Presunta etiología cardiaca de la embolia (como, por ejemplo, fibrilación auricular, prótesis valvulares conocidas o posible endocarditis).

Relacionados con la presencia de otros problemas médicos que puedan repercutir negativamente en la participación en el estudio o imposibilitar su finalización:
19) Mayor riesgo de hemorragia como, por ejemplo, insuficiencia hepática grave, úlcera péptica actual, retinopatía diabética proliferativa, antecedentes de hemorragia sistémica grave (por ejemplo, hemorragia digestiva, hematuria macroscópica, hemorragia intraocular, ictus hemorrágico sintomático o hemorragia intracraneal), u otros antecedentes de diátesis hemorrágica o coagulopatía.
20) Infarto de miocardio o angina estable concomitantes (o acaecidos en el mes anterior).
21) Presencia de una comorbilidad grave por la que no se espera que el paciente sobreviva 1 año, o que pueda influir negativamente en la evaluación de los criterios de valoración.
22) Cirugía programada que obligue a discontinuar el tratamiento con los medicamentos en investigación.
23) Administración de cualquier tratamiento en fase de investigación clínica (fármaco o producto sanitario) en los 30 días previos.
24) Factores geográficos o sociales que dificulten la participación en el estudio.
25) Incapacidad por parte del paciente de comprender el significado del consentimiento informado en su totalidad.

E.5 End points

E.5.1

Primary end point(s)

Variable principal de eficacia:
- Porcentaje de pacientes con un nuevo episodio vascular isquémico, definido como cualquier episodio del siguiente grupo:
o Nuevo infarto cerebral en RM cerebral.
o Nuevo ictus isquémico clínico.
o IM.
o Muerte por causas vasculares.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

Yes

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

Information not present in EudraCT

E.7.1.2

Bioequivalence study

Information not present in EudraCT

E.7.1.3

Other

Information not present in EudraCT

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

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

E.8.5

The trial involves multiple Member States

Yes

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

Information not present in EudraCT

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

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

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

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 months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

Information not present in EudraCT

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

Information not present in EudraCT

F.1.1.3

Newborns (0-27 days)

Information not present in EudraCT

F.1.1.4

Infants and toddlers (28 days-23 months)

Information not present in EudraCT

F.1.1.5

Children (2-11years)

Information not present in EudraCT

F.1.1.6

Adolescents (12-17 years)

Information not present in EudraCT

F.1.2

Adults (18-64 years)

Yes

F.1.3

Elderly (>=65 years)

Yes

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

140

F.4.2

For a multinational trial

F.4.2.1

In the EEA

1535

F.4.2.2

In the whole clinical trial

2400

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

No hay recomendaciones específicas, después de la finalización del estudio según la experiencia del investigador

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2006-09-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2006-08-11

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-07-20

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