Clinical Trials Register

Summary
EudraCT Number:	2019-001336-62
Sponsor's Protocol Code Number:	2019-ASPIREAF
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2022-01-27
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

2019-001336-62

A.3

Full title of the trial

Anticoagulation for Stroke Prevention In patients with Recent Episodes of perioperative Atrial Fibrillation after noncardiac surgery - The ASPIRE-AF trial

USO DI NUOVI ANTICOAGULANTI ORALI (NOAC) PER LA PREVENZIONE DELL'ICTUS IN PAZIENTI CON RECENTI EPISODI DI FIBRILLAZIONE ATRIALE PERIOPERATORIA DOPO CHIRURGIA NON CARDIACA.

A.3.1

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

Anticoagulation for Stroke Prevention In patients with Recent Episodes of perioperative Atrial Fibrillation after noncardiac surgery - The ASPIRE-AF trial

USO DI NUOVI ANTICOAGULANTI ORALI (NOAC) PER LA PREVENZIONE DELL'ICTUS IN PAZIENTI CON RECENTI EPISODI DI FIBRILLAZIONE ATRIALE PERIOPERATORIA DOPO CHIRURGIA NON CARDIACA.

A.3.2

Name or abbreviated title of the trial where available

ASPIRE-AF Trial

ASPIRE-AF

A.4.1

Sponsor's protocol code number

2019-ASPIREAF

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	Population Health Research Institute
B.1.3.4	Country	Canada
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	Population Health Reserarch Institute.
B.4.2	Country	Canada
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Istituto di Ricerche Farmacologiche Mario Negri
B.5.2	Functional name of contact point	Dipartimento Medicina Cardiovascola
B.5.3	Address:
B.5.3.1	Street Address	Via Mario Negri, 2
B.5.3.2	Town/ city	Milano
B.5.3.3	Post code	20156
B.5.3.4	Country	Italy
B.5.4	Telephone number	0239014508
B.5.5	Fax number	0233200049
B.5.6	E-mail	lidia.staszewsky@marionegri.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	ELIQUIS - 5 MG - COMPRESSA RIVESTITA CON FILM - USO ORALE - BLISTER (PVC/PVDC/ALU) - 20 COMPRESSE
D.2.1.1.2	Name of the Marketing Authorisation holder	BRISTOL-MYERS SQUIBB / PFIZER EEIG
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	ELIQUIS
D.3.2	Product code	[B01AF02]
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	APIXABAN
D.3.9.1	CAS number	503612-47-3
D.3.9.2	Current sponsor code	APIXABAN
D.3.9.3	Other descriptive name	APIXABAN
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	5
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	Pradaxa
D.2.1.1.2	Name of the Marketing Authorisation holder	Boehringer Ingelheim International GmbH
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	PRADAXA
D.3.2	Product code	[B01AE07]
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	DABIGATRAN ETEXILATO
D.3.9.1	CAS number	211915-06-9
D.3.9.2	Current sponsor code	DABIGATRAN
D.3.9.3	Other descriptive name	DABIGATRAN
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	110
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
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: 3
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	XARELTO - 20 MG - COMPRESSA RIVESTITA CON FILM - USO ORALE - BLISTER (PP/ALU) 28 COMPRESSE
D.2.1.1.2	Name of the Marketing Authorisation holder	BAYER PHARMA AG
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	RIVAROXABAN
D.3.2	Product code	[B01AF01]
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	RIVAROXABAN
D.3.9.1	CAS number	366789-02-8
D.3.9.2	Current sponsor code	RIVAROXABAN
D.3.9.3	Other descriptive name	RIVAROXABAN
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	20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
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: 4
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	LIXIANA - 60 MG - COMPRESSA RIVESTITA CON FILM - USO ORALE - BLISTER (PVC/ALLUMINIO) - 28 COMPRESSE
D.2.1.1.2	Name of the Marketing Authorisation holder	DAIICHI SANKYO EUROPE GMBH
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	EDOXABAN TOSILATO
D.3.2	Product code	[edoxaban]
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	EDOXABAN TOSILATO
D.3.9.1	CAS number	480449-70-5
D.3.9.2	Current sponsor code	EDOXABAN TOSILATO
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	60
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
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

Atrial Fibrillation perioperative after noncardiac surgery

Fibrillazione atriale perioperatoria post chirurgia non cardiaca

E.1.1.1

Medical condition in easily understood language

Atrial Fibrillation perioperative after noncardiac surgery

Fibrillazione atriale perioperatoria post chirurgia non cardiaca

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	10016566
E.1.2	Term	Fibrillation atrial
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

To assess the effects of non-vitamin K oral anticoagulants (NOACs) versus no anticoagulation on the co-primary composite outcomes of 1. non-hemorrhagic stroke and systemic embolism, and 2. vascular mortality, and non-fatal non-hemorrhagic stroke, myocardial infarction, peripheral arterial thrombosis, amputation, and symptomatic venous thromboembolism 24 months after randomization.

Valutare gli effetti degli anticoagulanti orali non antagonisti della vitamina K (NOAC) sugli outcome compositi co-primari di 1. ictus non emorragico ed embolia sistemica e 2. mortalità cardiovascolare, ictus non emorragico non fatale, infarto miocardico acuto, trombosi arteriosa periferica, amputazione, e tromboembolia venosa sintomatica a 24 mesi dalla randomizzazione.

E.2.2

Secondary objectives of the trial

To assess the effects of NOACs on the incidence of the following outcomes 24 months after randomization: 1. individual components of the co-primary outcomes; 2. all-cause stroke; and 3. all-cause mortality

Valutare gli effetti dei NOAC sull’incidenza dei seguenti outcome a 24 mesi dalla randomizzazione: 1. componenti individuali degli outcome co-primari; 2. ictus per tutte le cause; e 3. mortalità per tutte le cause.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patients are eligible if they: 1. underwent noncardiac surgery with at least an overnight hospital admission after surgery in the last 35 days;
2. have had =1 episode of clinically important perioperative atrial fibrillation or flutter (AF);
3. are in sinus rhythm at the time of randomization;
4. have any of the following high-risk criteria: a. age 55-74 years plus either established cardiovascular disease, recent major vascular surgery, or a CHA2DS2VASc score =3; or b. age =75 years;
5.provide written informed consent

Un paziente è eleggibile se:
1. È stato sottoposto a chirurgia non cardiaca e ha trascorso almeno una notte in ospedale dopo l’operazione negli ultimi 35 giorni;
2. Ha avuto =1 episodio di fibrillazione atriale perioperatoria o flutter atriale (FA);
3. Presenta ritmo sinusale al momento della randomizzazione;
4. Presenta uno dei seguenti criteri di alto rischio:
a. Età 55-74 con cardiopatia accertata, recente chirurgia vascolare importante o CHA2DS2VASc score =3;
b. Età=75;
5. Fornisce un consenso informato scritto.

E.4

Principal exclusion criteria

Patients are excluded if they fulfill any of the following criteria: 1. have a history of documented AF before noncardiac surgery; 2. need long-term therapeutic anticoagulation (e.g., mechanical valve); 3. ongoing need for long-term dualantiplatelet treatment; 4. have a contraindication to anticoagulation; 5. have severe renal insufficiency (i.e., eGFR <30 ml/min); 6. have had an acute stroke in the preceding 3 months; 7. underwent cardiac surgery in the preceding 3 months; 8.have a history of intracranial, intraocular, or spinal bleeding; 9. have hemorrhagic disorder or bleeding diathesis; 10. are expected to be non-compliant with follow-up;11. have a known life expectancy of <1 year due to concomitant disease; 12. women who are pregnant, breastfeeding, or of childbearing potential and not taking effective contraception; or 13. were previously enrolled in the trial

Un paziente è escluso se soddisfa uno dei seguenti criteri:
1. Storia di FA documentata prima dell’operazione chirurgica non cardiaca;
2. Necessità di terapia anticoagulante a lungo termine (es. valvola meccanica);
3. Necessità di doppia terapia antiaggregante a lungo termine;
4. Controindicazione agli anticoagulanti;
5. Insufficienza renale grave (i.e., eGFR<30ml/min);
6. Ha avuto un ictus acuto nei tre mesi precedenti;
7. È stato sottoposto a una chirurgia cardiaca nei tre mesi precedenti;
8. Storia di emorragia intracranica, intraoculare o spinale;
9. Disturbi emorragici o diatesi emorragica;
10. Si presume non rispetti i follow-up;
11. Aspettativa di vita < 1 anno a causa di patologie concomitanti;
12. Gravidanza, allattamento, età fertile e mancato uso di contraccettivi efficaci;
13. Partecipazione a un altro studio clinico.

E.5 End points

E.5.1

Primary end point(s)

E.5.1.1

Timepoint(s) of evaluation of this end point

24 months

24 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

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

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)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

TERAPIA STANDARD DELLA FIBRILLAZIONE ATRIALE

standard care

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

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

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

Australia

Canada

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

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.1.1.1

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

Yes

F.3.3.1

Women of childbearing potential not using contraception

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

500

F.4.2.2

In the whole clinical trial

2800

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)

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

2022-05-24

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-12-22

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

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