Clinical Trials Register

Summary
EudraCT Number:	2015-003621-33
Sponsor's Protocol Code Number:	ESR-15-10793
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2016-02-03
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

2015-003621-33

A.3

Full title of the trial

PRotective Effect on the coronary microcirculation of patients with DIabetes by Clopidogrel or Ticagrelor:A randomized multicenter clinical trial using intracoronary multimodal physiology

Efecto protector de la microcirculación coronaria de Clopidogrel o Ticagrelor en pacientes con diabetes: Ensayo clínico multicéntrico aleatorizado usando fisiología intracoronaria multimodal

A.3.1

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

Protective effect of antiplatelet drug "Ticagrelor" compared to antiplatelet drug "Clopidogrel" on small heart vessels in diabetic patient with angina

Efecto protector del fármaco antiplaquetario "Ticagrelor" en comparación con el fármaco antiplaquetario "Clopidogrel" en los pequeños vasos cardíacos en pacientes diabéticos con angina de pecho

A.3.2

Name or abbreviated title of the trial where available

PREDICT

A.4.1

Sponsor's protocol code number

ESR-15-10793

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	Fundación Interhospitalaria de Investigación Cardiovascular
B.1.3.4	Country	Spain
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	AstraZeneca Farmacéutica Spain, S.A.
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Hospital Clinico San Carlos
B.5.2	Functional name of contact point	Unidad de Hemodinámica
B.5.3	Address:
B.5.3.1	Street Address	Calle Profesor Martin 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	+34913303438
B.5.5	Fax number	+34915499793
B.5.6	E-mail	javier.escaned@salud.madrid.org

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
D.2.1.1.2	Name of the Marketing Authorisation holder	AstraZeneca Farmacéutica Spain, S.A.
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	Brilique
D.3.2	Product code	Brilique
D.3.4	Pharmaceutical form	Film-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	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	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	Plavix
D.3.2	Product code	Plavix
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	Clopidogrel
D.3.9.3	Other descriptive name	CLOPIDOGREL
D.3.9.4	EV Substance Code	SUB13395MIG
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)	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

Ischemic Heart Disease in Diabetic patients

Cardiopatía isquémica en pacientes diabéticos

E.1.1.1

Medical condition in easily understood language

Small Heart vessels disease in diabetic patients

Enfermedad en los vasos pequeños del corazón en pacientes diabéticos

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.1
E.1.2	Level	PT
E.1.2	Classification code	10072685
E.1.2	Term	Microvascular coronary artery disease
E.1.2	System Organ Class	10007541 - Cardiac disorders

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 investigate the protective effect of Ticagrelor on microcirculation during Percutaneous Coronary Intervention (PCI) in patients with Diabetes Mellitus (DM) or pre-DM

Investigar el efecto protector del Ticagrelor en la microcirculación durante la ICP en pacientes con DM o pre-DM

E.2.2

Secondary objectives of the trial

Not applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

? Subject with Diabetes Mellitus Type II or pre-Diabetes Mellitus Type II status.
? Subject must be older than 18 years.
? Written informed consent available.
?Subject with stable ischemic heart disease referred for coronary angiography.
? Subject is eligible for PCI.

+ Sujetos con Diabetes Mellitus tipo II o pre-Diabetes Mellitus tipo II.
+ Sujetos mayores de 18 años.
+ Consentimiento informado firmado.
+ Pacientes con cardiopatía isquémica estable enviados para la realización de coronariografía.
+ Pacientes aptos para ICP.

E.4

Principal exclusion criteria

? Prior myocardial infarction in the territory of the target vessel.
? Akinesia or dyskinesia in subtended myocardial segments.
? Severe impairment of left ventricular function (LVEF <35%).
? PCI target is a Chronic Total Occlusion.
? Target lesion has been treated previously (restenotic lesions).
? Target vessel is a saphenous vein graft or a surgical graft has been anastomosed to target vessel.
? TIMI flow ? 1 prior to guide wire crossing.
? Subject is not eligible for treatment with DES.
? Bleeding disorders or chronic anticoagulant treatment.
? Left main stenosis > 50%.
? Coronary surgery deemed more beneficial for the patient than PCI.
? Intolerance or contraindications to anti-platelet drugs.
? Contraindications for adenosine administration.
? Platelet count <75000 or >700000/mm3.
? Immunosuppressive therapy.
? Pregnant or breast feeding patient.
? History of intracranial haemorrhage.
? Severe hepatic impairment.

+ Infarto de miocardio previo en el territorio del vaso objetivo.
+ Akinesia o diskinesia en los segmentos miocárdicos subyacentes.
+ Lesión severa de la función ventricular izquierda (FEVI < 35%).
+ La lesión objetivo es una oclusión total crónica.
+ Lesión objetivo tratada previamente.
+ El vaso objetivo es un injerto de una vena safena o un injerto quirúrgico se ha anastomosado al vaso objetivo.
+ Flujo TIMI < 1 antes de cruzar la guía de presión.
+ El sujeto no es apto para ser tratado con DES.
+ Desordenes de sangrado o tratamiento anticoagulante crónico.
+ Estenosis de Tronco Comun mayor del 50%
+ Cirugía coronaria más beneficiosa para el paciente que la ICP.
+ Intolerancia o contraindicaciones al tratamiento antiplaquetario.
+ Contraindicaciones a la administración de adenosina.
+ Número de plaquetas < 75000 o > 700000/mm3.
+ Terapia inmunodepresiva.
+ Embarazo o lactancia.
+ Historia de hemorragia intracraneal.
+ Disfunción hepática severa.

E.5 End points

E.5.1

Primary end point(s)

1. Difference in microcirculatory resistance associated to PCI in DM or pre-DM patients treated with Ticagrelor or Clopidogrel (delta IMR-Post-PCI).
2. Difference in microcirculatory resistance associated to the initiation of Ticagrelor treatment in DM or pre-DM (delta IMR-Pre-PCI).

1. La diferencia en la resistencia de la microcirculación asociada a la ICP en pacientes con DM o pre-DM tratados con Ticagrelor o Clopidogrel (delta IMR-post-ICP).
2. La diferencia en la resistencia de la microcirculación asociada al inicio del tratamiento con Ticagrelor en pacientes con DM o pre-DM (delta IMR-pre-ICP).

E.5.1.1

Timepoint(s) of evaluation of this end point

1. Post PCI (just after stenting)
2. Pre PCI (just before stenting)

1. Después de la ICP (justo después de implantar el stetn)
2. Antes de la ICP (justo antes de implantar el stent)

E.5.2

Secondary end point(s)

1. Myocardial necrosis associated to PCI damage, as assessed by cardiac markers in DM or pre-DM patients treated with Ticagrelor or Clopidogrel.
2. Absolute IMR value after PCI in DM or pre-DM patients treated with Ticagrelor or Clopidogrel.
3. Incidence (%) of severe microcirculatory impairment (IMR > 29) afer PCI in DM or pre-DM patients treated with Ticagrelor or Clopidogrel.

1. Necrosis miocárdica asociada al daño por ICP, evaluada por medio de marcadores cardiacos en pacientes con DM o pre-DM tratados con Ticagrelor o Clopidogrel.
2. Valor absoluto del valor de IMR después de la ICP en pacientes con DM o pre-DM tratados con Ticagrelor o Clopidogrel.
3. Incidencia (%) de lesión severa microcirculatoria (IMR > 29) después de la ICP en pacientes con DM o pre-DM tratados con Ticagrelor o Clopidogrel.

E.5.2.1

Timepoint(s) of evaluation of this end point

1. At discharge
2. Post PCI
3. Post PCI

1. Al alta
2. Después de la ICP
3. Después de la ICP

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

Yes

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

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

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

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

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)

None

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

2016-02-25

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-12-17

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2019-04-24

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