Clinical Trials Register

Summary
EudraCT Number:	2014-005363-33
Sponsor's Protocol Code Number:	ESR-14-10048
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2016-02-24
Trial 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

2014-005363-33

A.3

Full title of the trial

Reducing Micro Vascular dysfunction In revascularized STEMI patients by off-target properties of ticagrelor

Reducción de disfunción microvascular en pacientes con STEMI revascularizado por propiedades off-target de ticagrelor

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Discovering beneficial properties of ticagrelor in acute myocardial
infarction

Descubriendo las propiedades beneficiosas de ticagrelor en el infarto agudo de miocardio

A.3.2

Name or abbreviated title of the trial where available

REDUCE-MVI

A.4.1

Sponsor's protocol code number

ESR-14-10048

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	VU university medical center
B.1.3.4	Country	Netherlands
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	VU university medical center
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Hospital Clínico San Carlos
B.5.2	Functional name of contact point	Unidad de Ensayos Clínicos
B.5.3	Address:
B.5.3.1	Street Address	C/Profesor Martín Lagos, s/n
B.5.3.2	Town/ city	Madrid
B.5.3.3	Post code	28040
B.5.3.4	Country	Spain
B.5.4	Telephone number	+34913303793
B.5.5	Fax number	+31204443984
B.5.6	E-mail	m.vanleeuwen@vumc.nl

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	Brilique 90 mg film coated tablets
D.2.1.1.2	Name of the Marketing Authorisation holder	AstraZeneca AB
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Ticagrelor / brilique
D.3.4	Pharmaceutical form	Coated tablet
D.3.4.1	Specific paediatric formulation	No
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	Ticagrelor
D.3.9.1	CAS number	274693-27-5
D.3.9.3	Other descriptive name	TICAGRELOR
D.3.9.4	EV Substance Code	SUB30898
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	90
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)	No
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	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
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	No
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	Yes
D.2.1.1.1	Trade name	Prasugrel / efient
D.2.1.1.2	Name of the Marketing Authorisation holder	Eli Lilly Nederland BV
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	efient
D.3.2	Product code	EU/1/08/503/015
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
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	PRASUGREL
D.3.9.1	CAS number	150322-43-3
D.3.9.4	EV Substance Code	SUB30236
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	10
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)	No
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	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
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	No
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

ST elevation myocardial infarction (STEMI)

Infarto de miocardio con elevación del ST

E.1.1.1

Medical condition in easily understood language

heart attack

ataque al corazón

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To determine if ticagrelor at treatment steady state (30 days
maintenance therapy) will be associated to an improved microvascular
function as compared to prasugrel in revascularized STEMI patients.

Determinar si ticagrelor en fase estable de tratamiento (terapia de mantenimiento de 30 días) se asociará a una función microvascular mejorada en comparación con prasugrel en pacientes con STEMI revascularizado

E.2.2

Secondary objectives of the trial

Not applicable

No aplicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Provision of informed consent
2. Patients presenting with STEMI <12 hours
3. Successful PCI of the infarct-related vessel with a modern DES
4. Intermediate stenosis in non-infarct-related vessel (50-90%)

1. Provisión de consentimiento informado.
2. Pacientes que se presentan con un STEMI < 12 horas
3. ICP del vaso relacionado con el infarto con éxito con un stent liberador de fármaco (DES) moderno.
4. Estenosis intermedia en un vaso no relacionado con el infarto (50-90%).

E.4

Principal exclusion criteria

1. history of myocardial infarction
2. Participation in another clinical study with an investigational product
during the preceding 30 days
3. history of cerebrovascular accident (CVA) or 'transient ischaemic
attack' (TIA)
4. History of intracranial haemorrhage
5. indication or use of oral anticoagulant therapy (i.e. acenocoumarol)
6. severe liver dysfunction (Child-Pughscore 10?15)
7. congestive heart failure
8. cardiogenic shock
9. left ventricular ejection fraction < 35%
10. bleeding diathesis
11. age ? 75 or < 18
12. body weight < 60 kg
13. gout
14. coagulation disorders
15. severe pulmonary disease
16. pregnancy and breast feeding
17. limited life expectancy
18. platelet count < 100 000/mm3
19. history of drug addiction or alcohol abuse in the past 2 years
20. need for chronic nonsteroidal anti-inflammatory drug
21. creatinine clearance <30 mL/min or dialysis
22. chronic total occlusion (CTO)
23. Left main disease
24. allergy or contra-indication for ticagrelor or prasugrel
25. Contra-indication for adenosine
26. Patients unable to be followed on-site
27. Unable to undergo or contra-indications for MRI
28. Contra-indication for DES
29. Inability to obtain informed consent

1. infarto previo.
2. participación en otro ensayo clínico con un producto de investigación en los 30 días precedentes.
3. accidente cerebrovascular (ACV) previo o ataque isquémico transitorio (AIT).
4. Historia de hemorragia intracraneal.
5. Indicación o uso de terapia anticoagulante (i.e. acenocoumarol).
6. Disfunción de hígado severa (Child-Pughscore 10?15).
7. Insuficiencia cardiaca congestiva.
8. Shock cardiogénico.
9. Fracción de eyección del ventrículo izquierdo < 35%
10. diátesis hemorrágica
11. Edad >= 75 o <18
12. Peso < 60 Kg
13. Gota
14. Desorden en la coagulación.
15. Enfermedad pulmonar severa.
16. Embarazo y lactancia.
17. Esperanza de vida limitada.
18. Conteo plaquetario < 100 000/mm3.
19. Historia de drogadicción o abuso del alcohol en los últimos 2 años.
20. Necesidad de medicamento anti-inflamatorio no-esteroidal crónico.
21. Aclaramiento de creatinina <30 mL/min o diálisis.
22. Oclusión total crónica.
23. Enfermedad de la arteria coronaria izquierda principal.
24. Alergia o contraindicación a ticagrelor o prasugrel.
25. Contraindicación a la adenosina.
26. Pacientes que no puedan acudir al seguimiento en el centro
27. Pacientes incapaces de hacerse o con contraindicación a resonancia magnética.
28. Contraindicación a DES (stents liberadores de fármaco).
29. Incapacidad de obtener el consentimiento informado.

E.5 End points

E.5.1

Primary end point(s)

Index of microcirculatory resistance (IMR) at treatment steady state (1
month after primary PCI) in the infarct-related vessel, assessed with a
pressure wire (Certus, St Jude Medical, St Paul,MN, USA).

Índice de resistencia microcirculatoria (IMR) en un momento estacionario del tratamiento (1 mes después de la ICP) en el vaso relacionado con el infarto, medido con una guía de presión (Certus, St Jude Medical, St Paul,MN, USA).

E.5.1.1

Timepoint(s) of evaluation of this end point

1 month after primary PCI

1 mes después de la ICP primaria

E.5.2

Secondary end point(s)

- The reactive hyperemia index (RHI) at treatment steady state (1 month
after primary PCI), assessed
with endopath system (Endopath; Itamar Medical Ltd., Cesarea, Israel).
- The delta IMR between baseline and follow-up in both the infarctrelated
vessel and non-infarct related vessel.
- The delta RHI between baseline and follow-up
- The level of endothelial function as measured by several parameters
(endothelin-1, NO synthase, e-NOS and dimethylarginine ) at follow-up

- Índice de hiperemia reactiva (RHI) en un momento estacionario del tratamiento (1 mes después de la ICP primaria), medido con el sistema endopath (Endopath; Itamar Medical Ltd., Cesarea, Israel).
- Diferencia entre IMR basal y en el seguimiento, tanto en el vaso relacionado con el infarto como en el no relacionado.
- Diferencia entre RHI basal y RHI al seguimiento.
- Nivel de función endotelial medida por varios parámetros (endothelin-1, NO synthase, e-NOS y dimethylarginine ) al seguimiento

E.5.2.1

Timepoint(s) of evaluation of this end point

- RHI: Baseline (1 day after primary PCI) and follow-up (1 month and 1
year)
- IMR: Baseline (directly after primary PCI) and follow-up ( 1 month)
- Endothelial function blood samples: Baseline (directly after primary
PCI) and follow-up (3 days, 1 month and 1 year)

- RHI: Basal (1 día después de la ICP primaria) y en el seguimiento (1 mes y 1 año).
- IMR: Basal (justo después de la ICP primaria) y al seguimiento (1 mes)
- Función endotelial de muestras de sangre: Basal (justo después de la ICP primaria) y al seguimiento (3 dias, 1 mes y 1 año).

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

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

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

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

E.8.1.4

Double blind

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.8.2.4

Number of treatment arms in the trial

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

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

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

LVLS

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 years

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

F.1.1.2

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

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

110

F.4.2

For a multinational trial

F.4.2.1

In the EEA

110

F.4.2.2

In the whole clinical trial

110

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)

After the subject has ended the participation in the trial, treatment and
care will be left to the treating physician

Después de que el sujeto haya finalizado con la participación en el ensayo, el tratamiento y los cuidados se dejarán a la elección de su médico

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

2016-03-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-12-18

P. End of Trial
P.	End of Trial Status	Ongoing

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