Clinical Trials Register

Summary
EudraCT Number:	2016-004746-28
Sponsor's Protocol Code Number:	POR-TAP-16-007
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2019-03-14
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2016-004746-28

A.3

Full title of the trial

Ticagrelor And PrEconditioning in patients with stable coronaRy artery diSease:
a randomized pilot trial (TAPER-S trial)

Ticagrelor e precondizionamento in pazienti con malattia coronarica stabile: studio pilota randomizzato (Studio TAPER-S)

A.3.1

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

A.3.2

Name or abbreviated title of the trial where available

TAPER-S

A.4.1

Sponsor's protocol code number

POR-TAP-16-007

A.5.4

Other Identifiers

Name:

Number:

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	UNIVERSITÀ CATTOLICA DEL SACRO CUORE- POLICLINICO A. GEMELLI
B.1.3.4	Country	Italy
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
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	CLINICAL TRIAL CENTER
B.5.2	Functional name of contact point	CRO ACCADEMICA
B.5.3	Address:
B.5.3.1	Street Address	LARGO AGOSTINO GEMELLI, 8
B.5.3.2	Town/ city	ROMA
B.5.3.3	Post code	00168
B.5.3.4	Country	Italy
B.5.4	Telephone number	0688805566
B.5.5	Fax number	0688805567
B.5.6	E-mail	betty.polikar@policlinicogemelli.it

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 - COMPRESSE RIVESTITE CON FILM - USO ORALE - BLISTER(PVC/PVDC/ALU) 60 COMPRESSE
D.2.1.1.2	Name of the Marketing Authorisation holder	ASTRAZENECA AB
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP
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.3.9.2	Current sponsor code	ND
D.3.9.3	Other descriptive name	TICAGRELOR
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
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	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 - 75 28 COMPRESSE FILMRIVESTITE 75 MG IN BLISTER
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	Italy
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	ND
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
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CLOPIDOGREL
D.3.9.1	CAS number	120202-66-6
D.3.9.2	Current sponsor code	ND
D.3.9.3	Other descriptive name	CLOPIDOGREL
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
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	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

Patients with multivessel coronary artery disease requiring staged, ischemia-guided PCI

Pazienti con malattia coronarica multivasale che richiedono PCI guidata

E.1.1.1

Medical condition in easily understood language

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	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10074572
E.1.2	Term	Multiple vessel coronary artery disease
E.1.2	System Organ Class	100000004849

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Ticagrelor may trigger ischemic preconditioning as compared to clopidogrel in patients with stable coronary disease, showing multivessel coronary artery disease and undergoing staged PCI

Ticagrelor potrebbe attivare il precondizionamento ischemico comparato a clopidogrel in pazienti con malattia coronarica stabile, mostrando malattia coronarica arteriosa multivasale e sottoposti a PCI.

E.2.2

Secondary objectives of the trial

Ticagrelor may improve microvascular perfusion in the myocardium of patients with multivessel coronary artery disease undergoing staged PCI

Ticagrelor potrebbe migliorare la perfusione microvascolare nel miocardio dei pazienti con malattia coronarica multivasale sottoposti a PCI.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Signed and dated Informed Consent obtained prior to the inclusion in the trial
2. Age > 18 and < 75 years (both inclusive)
3. Weight > 60 Kg (inclusive)
4. Patients must have a clinical indication to undergo scheduled FFR-guided PCI. We will include two types of stable patients:
1) purely stable patients undergoing scheduled FFR-guided PCI of any vessel
2) patients presenting initially with acute coronary syndrome, with an intermediate coronary lesion (40%-80% in severity, where functional evaluation with FFR must be used on clinical grounds) in a non-culprit artery, and needing staged FFR-guided PCI (at least one month after the ACS)
5. Patients may be already on treatment with either Ticagrelor (mainly previous ACS patients) or Clopidogrel (purely stable patients)

1. Consenso Informato firmato e datato prima dell’inclusione nello studio
2. Età >18 e <75 anni (entrambi inclusi)
3. Peso >60 Kg (incluso)
4. I pazienti devono avere una indicazione clinica per essere sottoposti a PCI guidata da riserva di flusso. Saranno inclusi nello studio due tipologie di pazienti stabili:
1) pazienti perfettamente stabili che hanno bisogno della PCI guidata da riserva di flusso frazionale (almeno un mese dopo la sindrome coronarica acuta) sottoposti a schedulata PCI guidata da riserva di flusso frazionale per qualsiasi vaso
2) pazienti che si presentano inizialmente con una sindrome coronarica acuta, con una lesione coronarica intermedia (severità del 40-80%, dove la valutazione mediante la riserva di flusso frazionale deve essere usata per motivi clinici) nell’arteria non colpevole,
5. I pazienti possono essere già in trattamento sia con ticagrelor (principalmente pazienti con precedente sindrome coronarica acuta) o clopidogrel (pazienti perfettamente stabili)

E.4

Principal exclusion criteria

1. Known hypersensitivity to aspirin, clopidogrel, ticagrelor or any excipients
2. Concomitant oral anticoagulant therapy, or likely need for it (e.g. atrial fibrillation)
3. Need for concomitant cardiac procedure, such as valve repair or replacement
4. Any previous history of ischemic stroke, intracranial hemorrhage or disease (neoplasm, arteriovenous malformation, aneurysm)
5. Any active pathological bleeding or history of gastrointestinal bleeding, genitourinary bleeding or other site abnormal bleeding within the previous 3 months, other bleeding diathesis, or considered by investigator to be at high risk for bleeding
6. Concomitant oral or IV therapy with strong CYP3A inhibitors, CYP3A substrates with narrow therapeutic indices, or strong CYP3A inducers. Any of such concomitant treatment will be mapped and evaluated by the Investigator in order to comply with the exclusion criteria
7. Increased risk of bradycardia events
8. Known pregnancy and/or breast-feeding
9. Severe uncontrolled chronic obstructive pulmonary disease
10. Concomitant theophylline/aminophylline use
11. Baseline ECG with serious conduction abnormalities (i.e. LVH with repolarization abnormality, left bundle branch block, ST-segment
12. Evidence of prior myocardial infarction by cardiac imaging in the territory of the index vessel
13. Depressed left ventricular systolic function at randomization (ejection fraction < 40% within 48 hours before index PCI)
14. Clinical congestive heart failure
15. Presence of coronary collaterals on diagnostic coronary angiography
16. Diffuse obstructive disease (≥ 70% stenosis) in the distal segment of the target vessel
17. Left main and/or three-vessel coronary artery disease
18. End-stage renal disease
19. Known severe hepatic impairment

1. Conosciuta ipersensibilità all’aspirina, clopidogrel, ticagrelor o a uno qualsiasi degli eccipienti
2. Terapia anticoagulante concomitante, o probabilmente necessaria (fibrillazione atriale)
3. Necessità di procedure cardiache concomitanti, così come riparazione delle valvole o sostituzione
4. Una qualsiasi precedente storia di ictus ischemico, emorragia intracraniale o malattia (neoplasia, malformazione arteriovenosa, aneurisma)
5. Qualsiasi sanguinamento patologico attivo, o storia di sanguinamento gastrointestinale, genitourinario o un altro posto di sanguinamento anormale entro I precendenti 3 mesi, altre diatesi di spurgo, o considerate dal PI ad alto rischio di sanguinamento
6. Terapia orale concomitante con inibitori CYP3A, substrati CYP3A con indici terapeutici stretti, o forti induttori del CYP3A. Qualsiasi di questi trattamenti concomitanti verrà mappato e valutato dallo sperimentatore al fine di rispettare i criteri di esclusione
7. Incrementato rischio di eventi di bradicardia
8. Conosciuta gravidanza e/o allattamento
9. Severa, non controllata malattia cronica polmonare ostruttiva
10. Uso concomitante di
11. ECG alla visita basale con serie condizioni di anormalità
12. Evidence of prior myocardial infarction by cardiac imaging in the territory of the index vessel
13. depressa funzione sistolica ventricolare sinistra alla randomizzazione (frazione di eiezione < 40% entro 48 ore prima di indice PCI)
14. Insufficienza cardiaca congestizia
15. Presenza di collaterali coronarici su angiografia coronarica
16. Diffusa malattia ostruttiva (stenosi ≥ 70%) nel segmento distale del vaso bersaglio
17. Malattia dell'arteria coronaria principale e/o del tre-vaso a sinistra
18. Malattia renale di stadio finale
19. Grave insufficienza epatica

E.5 End points

E.5.1

Primary end point(s)

Delta (difference) ST-segment elevation by intracoronary ECG during two-step sequential coronary balloon inflation in the culprit vessel

Differenza di elevazione del tratto ST mediante ECG intracoronarico durante i due step di gonfiaggio del palloncino all’interno dell’arteria coronarica nel vaso colpevole.

E.5.1.1

Timepoint(s) of evaluation of this end point

20 months

20 mesi

E.5.2

Secondary end point(s)

Angina score during coronary balloon inflation

Score del dolore al petto durante il gonfiaggio del palloncino all’interno dell’arteria coronarica

E.5.2.1

Timepoint(s) of evaluation of this end point

20 months

20 mesi

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

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

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.8.5.1

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

Information not present in EudraCT

E.8.7

Trial has a data monitoring committee

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

CLINICAL STUDY REPORT COMPLETION

COMPLETAMENTO DEL CLINICAL STUDY REPORT

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

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1

Number of subjects for this age range:

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.1.2.1

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

Yes

F.3.3.1

Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2019-03-14.

Yes

F.3.3.2

Women of child-bearing potential using contraception

Yes

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

100

F.4.2

For a multinational trial

F.4.2.1

In the EEA

100

F.4.2.2

In the whole clinical trial

100

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)

NORMAL CLINICAL PRACTICE

NORMALE PRATICA CLINICA

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

2017-08-21

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-10-05

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2020-12-23

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