Clinical Trials Register

Summary
EudraCT Number:	2016-004510-99
Sponsor's Protocol Code Number:	012017POEM
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2018-09-14
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2016-004510-99

A.3

Full title of the trial

PERFORMANCE OF BIORESORBABLE POLYMER-COATED EVEROLIMUS-ELUTING SYNERGY® STENT IN PATIENTS AT HIGH BLEEDING RISK UNDERGOING PERCUTANEOUS CORONARY REVASCULARIZATION FOLLOWED BY 1-MONTH DUAL ANTIPLATELET THERAPY

A.3.1

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

Risultati della rivascolarizzazione percutanea con impianto di stent con rivestimento polimerico biodegradabile a rilascio di everolimus (Synergy®) in pazienti ad alto rischio di sanguinamento trattati con 1 mese di doppia terapia antiaggregante

A.3.2

Name or abbreviated title of the trial where available

POEM

A.4.1

Sponsor's protocol code number

012017POEM

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	IRCCS ISTITUTO CLINICO HUMANITAS
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	Boston Scientific S.p.A.
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	CD Pharma Group S.r.l.
B.5.2	Functional name of contact point	CRO
B.5.3	Address:
B.5.3.1	Street Address	Piazza Ernesto De Angeli, 7
B.5.3.2	Town/ city	Milano
B.5.3.3	Post code	20146
B.5.3.4	Country	Italy
B.5.4	Telephone number	+39 0289051076
B.5.5	Fax number	+39 0289051088
B.5.6	E-mail	simona.manzi@cdpharma.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) 56 COMPRESSE (CONF. CALENDARIZZATA)
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	Ticagrelor
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.3.9.2	Current sponsor code	Ticagrelor
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	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 - 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	Clopidogrel
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	CLOPIDOGREL
D.3.9.1	CAS number	113665-84-2
D.3.9.2	Current sponsor code	Clopidogrel
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

Coronary artery disease with high-bleeding risk (HBR)

Malattia coronarica associata ad alto rischio di sanguinamento

E.1.1.1

Medical condition in easily understood language

Coronary artery disease with high-bleeding risk (HBR)

Malattia coronarica associata ad alto rischio di sanguinamento

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	PT
E.1.2	Classification code	10011078
E.1.2	Term	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 evaluate the safety of bioresorbable polymer-coated everolimus-eluting Synergy® stent followed by 1-month dual antiplatelet therapy in patients at high-bleeding risk

Valutare la sicurezza della rivascolarizzazione con impianto di stent con rivestimento polimerico biodegradabile a rilascio di everolimus (Synergy®) seguita da 1 mese di doppia terapia antiaggregante in pazienti ad alto rischio di sanguinamento

E.2.2

Secondary objectives of the trial

To evaluate the safety of bioresorbable polymer-coated everolimus-eluting Synergy® stent followed by 1-month dual antiplatelet therapy in patients at high-bleeding risk

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

a) Written, signed informed consent;
b) Age ≥18 years;
c) Patients at high bleeding risk (HBR) with symptomatic coronary artery disease, including patients with chronic stable angina, silent ischemia, or acute coronary syndromes (including NSTE-ACS and STE-ACS);
d) Presence of one or more coronary artery stenoses >50% in a native coronary artery or a saphenous bypass graft that treated with one or multiple Synergy® stents;
e) PCI with the implantation of at least one Synergy® Stent System within 12 hours prior to inclusion
Moreover, in order to be included patients will need to meet at least 1 of the following HBR criteria:
1. Age ≥75 years
2. Oral anticoagulation planned to continue after PCI
3. Hemoglobin <11 g/l,
4. Transfusion within 4 week before inclusion
5. Platelet count <100’000/ml
6. Hospital admission for bleeding in previous 12 months
7. Stroke in previous 12 months
8. History of intracerebral hemorrhage
9. Severe chronic liver disease
10. Creatinine clearance <40 ml/min
11. Cancer in previous 3 years
12. Planned major surgery in next 12 months
13. Glucocorticoids or NSAID planned for >30 days after PCI
14. Expected non-adherence to >30 days of dual antiplatelet therapy

a) Firma del consenso informato scritto
b) Età ≥18 anni
c) Pazienti ad alto rischio di sanguinamento con malattia coronarica (con angina stabile, ischemia silente e sindromi coronariche acute con o senza sopraslivellamento del tratto ST)
d) Presenza di una o più stenosi dell’arteria coronarica > 50% in un’arteria coronarica nativa o un innesto di bypass della vena safena con impianto di 1 o più stent Synergy®
e) PCI con impianto di almeno uno stent Synergy® eseguito nelle 12 ore precedenti l’inclusione del paziente in Studio

I pazienti dovranno inoltre soddisfare almeno 1 dei seguenti criteri che identificano i pazienti ad alto rischio di sanguinamento:
1) Età ≥75 anni
2) Necessità di terapia anticoagulante orale
3) Emoglobina <11 g/l
4) Emotrasfusione nelle 4 settimane precedenti
5) Piastrinopenia (<100'000/ml)
6) Ricovero per sanguinamento nei 12 mesi precedenti
7) Ictus nei 12 mesi precedenti
8) Storia di sanguinamento intracranico
9) Epatopatia severa
10) Clearance creatinina <40 ml/min
11) Storia di neoplasia nei 3 anni precedenti
12) Programma di chirurgia maggiore nei 12 mesi successivi
13) Terapia con glucocorticoidi o antiinfiammatori non steroidei per >30 giorni dopo l’angioplastica
14) Prevista non adesione a una doppia terapia antiaggregante per oltre 30 giorni

E.4

Principal exclusion criteria

a) Cardiogenic shock
b) Major active bleeding at the time of PCI
c) Expected non-adherence with 1 month DAPT
d) Known intolerance to ASA, clopidogrel or ticagrelor or any of the excipients
e) Currently participating in another trial
f) Pregnancy or lactation
Note: there will be no exclusion based on mode of clinical presentation (with the exception of cardiogenic shock), co-morbidities, left ventricular function, number of diseased vessels and lesions, or number and type of target lesions

a) Shock cardiogeno
b) Sanguinamento attivo al momento dell’angioplastica
c) Prevista non adesione a una doppia terapia antiaggregante di almeno 1 mese
d) Nota intolleranza ad ASA, clopidogrel o ticagrelor o ad uno qualsiasi degli eccipienti
e) Partecipazione in altra sperimentazione clinica
f) Gravidanza o allatamento
Nota: non ci sarà esclusione basata sulla presentazione clinica (fatta eccezione per lo shock cardiogeno), co-morbidità, funzione ventricolare sinistra, numero di vasi danneggiati e lesioni, o numero e tipo di lesioni target

E.5 End points

E.5.1

Primary end point(s)

Composite of cardiac death, myocardial infarction, or definite/probable stent thrombosis at 1-year follow-up

Composito di mortalità per cause cardiovascolari, infarto del miocardio e trombosi di stent (definita/probabile secondo la definizione ARC) a 1 anno di follow-up

E.5.1.1

Timepoint(s) of evaluation of this end point

1-year

1 anno

E.5.2

Secondary end point(s)

- All-cause death at 30 days and 1 year
- Cardiac death at 30 days and 1 year
- Myocardial infarction (according to the III Universal Definition) Definite/probable stent thrombosis (according to ARC criteria) at 30 days and 1 year
- Definite stent thrombosis (according to ARC criteria) at 30 days and 1 year
- Target-vessel revascularization (any and clinically-driven) at 30 days and 1 year
- Target-lesion revascularization (any and clinically-driven) at 30 days and 1 year
- Major bleeding (BARC 3 to 5) at 30 days and 1 year
- Cerebrovascular events at 30 days and 1 year
- Target-lesion failure (composite of cardiac death, target-vessel myocardial infarction, or clinically-driven target lesion revascularization) at 30 days and 1 year
- Patient oriented composite endpoint (composite of any death, any MI, any revascularization) at 30 days and 1 year

- Mortalità per tutte le cause a 30 giorni e 1 anno
- Mortalità per cause cardiovascolari a 30 giorni e 1 anno
- Infarto del miocardio (secondo la III definizione universale) a 30 giorni e 1 anno
- Trombosi di stent (definita/probabile secondo la definizione ARC) a 30 giorni e 1 anno
- Trombosi di stent (definita secondo la definizione ARC) a 30 giorni e 1 anno
- Rivascolarizzazione del vaso target a 30 giorni e 1 anno
- Rivascolarizzazione della lesione target a 30 giorni e 1 anno
- Sanguinamenti maggiori (tipo 3-5 secondo la definizione BARC) a 30 giorni e 1 anno
- Eventi cerebrovascolari a 30 giorni e 1 anno
- Fallimento della lesione target (composito di mortalità per cause cardiovascolari, infarto miocardico imputabile al vaso target e rivascolarizzazione della lesione target indicata clinicamente) a 30 giorni e 1 anno
- Endpoint composito orientato al paziente (composito di mortalità per ogni causa, qualisasi infarto miocardico e qualsiasi revascolarizzazione ripetuta) a 30 giorni e 1 anno

E.5.2.1

Timepoint(s) of evaluation of this end point

30 days and 1 year

30 giorni e 1 anno

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

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

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Information not present in EudraCT

E.8.1.6

Cross over

Information not present in EudraCT

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

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

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

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:

323

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

700

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 2018-09-14.

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

Yes

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

1023

F.4.2

For a multinational trial

F.4.2.1

In the EEA

1023

F.4.2.2

In the whole clinical trial

1023

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)

The subjects, at the end of the participation in the trial, will be followed according to the normal clinical practice

I pazienti al termine della sperimentazione saranno seguiti in accordo alla 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

2017-02-06

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-02-21

P. End of Trial
P.	End of Trial Status	Completed

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IMP with orphan designation in the indication
Orphan Designation Number:
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