Clinical Trials Register

Summary
EudraCT Number:	2014-005569-58
Sponsor's Protocol Code Number:	BAY59-7939/17454
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:	2021-06-08
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

2014-005569-58

A.3

Full title of the trial

An international, multicenter, randomized, double-blind, placebo-controlled phase 3 trial investigating the efficacy and safety of rivaroxaban to reduce the
risk of major thrombotic vascular events in patients with symptomatic peripheral artery disease undergoing lower extremity revascularization
procedures.

Sperimentazione di fase 3 internazionale, multicentrica, randomizzata, in doppio cieco, controllata verso placebo volta a studiare l¿efficacia e la sicurezza di rivaroxaban per ridurre il rischio di eventi vascolari trombotici maggiori in pazienti affetti da arteriopatia periferica sintomatica sottoposti a procedure di rivascolarizzazione delle estremit¿ inferiori.

A.3.1

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

Vascular Outcomes studY of ASA alonG with rivaroxaban in Endovascular or surgical limb Revascularization for peripheral artery disease (PAD).

Studio degli esiti vascolari di ASA insieme a rivaroxaban nella rivascolarizzazione endovascolare o chirurgica degli arti per arteriopatia periferica (PAD).

A.3.2

Name or abbreviated title of the trial where available

VOYAGER PAD

A.4.1

Sponsor's protocol code number

BAY59-7939/17454

A.5.4

Other Identifiers

Name:

BAY 59-7939/17454

Number:

BAY 59-7939/17454

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	BAYER AG
B.1.3.4	Country	Italy
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Bayer HealthCare AG
B.4.2	Country	Germany
B.4.1	Name of organisation providing support	Janssen Research & Development, LLC
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Bayer HealthCare AG
B.5.2	Functional name of contact point	Bayer Clinical Trials Contact
B.5.3	Address:
B.5.3.1	Street Address	CTP Team/Ref:"EU CTR"/ Bayer Pharma AG
B.5.3.2	Town/ city	Berlin
B.5.3.3	Post code	13342
B.5.3.4	Country	Germany
B.5.4	Telephone number	214301
B.5.5	Fax number	214301
B.5.6	E-mail	clinical-trials-contact@bayerhealthcare.com

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	Xarelto 2.5 mg film-coated tablets
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 2.5mg
D.3.2	Product code	BAY 59-7939
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	RIVAROXABAN
D.3.9.1	CAS number	366789-02-8
D.3.9.2	Current sponsor code	BAY 59-7939
D.3.9.3	Other descriptive name	RIVAROXABAN
D.3.9.4	EV Substance Code	SUB29263
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	2
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Peripheral artery disease

arteriopatia periferica

E.1.1.1

Medical condition in easily understood language

Peripheral artery disease

arteriopatia periferica

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	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10053375
E.1.2	Term	Peripheral revascularization
E.1.2	System Organ Class	100000004865

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 whether rivaroxaban added to acetylsalicylic acid (ASA) is
superior to ASA alone in reducing the risk of major thrombotic vascular
events (defined as myocardial infarction (MI), ischemic stroke,
cardiovascular (CV) death, acute limb ischemia (ALI), and
major amputation of a vascular etiology) in symptomatic PAD patients
undergoing lower extremity revascularization procedure. To evaluate the overall safety and tolerability of rivaroxaban added to
ASA compared to ASA alone.

valutare se rivaroxaban aggiunto all¿acido acetilsalicilico (ASA) ¿ superiore
ad ASA in monoterapia nella riduzione del rischio di eventi vascolari
trombotici maggiori (definiti come infarto miocardico (IM), ictus ischemico,
morte cardiovascolare (CV), ischemia acuta degli arti (ALI) e amputazione
maggiore di eziologia vascolare) in pazienti affetti da arteriopatia periferica
(PAD) sintomatica sottoposti a procedura di rivascolarizzazione delle
estremit¿ inferiori.

E.2.2

Secondary objectives of the trial

- To evaluate whether rivaroxaban added to ASA is superior to ASA alone
in reducing the risk of index limb revascularization;
- To evaluate whether rivaroxaban added to ASA is superior to ASA alone
in reducing the risk of MI, ischemic stroke, coronary heart disease
mortality, ALI, and major amputation of a vascular etiology;
- To evaluate whether rivaroxaban added to ASA is superior to ASA alone
in reducing the risk of MI, ischemic stroke, all-cause mortality, ALI, and
major amputation of a vascular etiology;
- To evaluate whether rivaroxaban added to ASA is superior to ASA alone
in reducing the risk of vascular hospitalizations for a coronary or
peripheral event (either limb) of a thrombotic nature;
- To evaluate whether rivaroxaban added to ASA is superior to ASA alone
in reducing the risk of MI, all-cause stroke, CV death, ALI, and major
amputation of a vascular etiology;
- To evaluate the efficacy of rivaroxaban in reducing the risk of venous
thromboembolic (VTE) events;

valutare se rivaroxaban aggiunto ad ASA ¿ superiore ad ASA in
monoterapia nella riduzione del rischio di rivascolarizzazione dell¿arto
indice;
¿ valutare se rivaroxaban aggiunto ad ASA ¿ superiore ad ASA in
monoterapia nella riduzione del rischio di IM, ictus ischemico, mortalit¿
dovuta a coronaropatia, ALI e amputazione maggiore di eziologia vascolare;
¿ valutare se rivaroxaban aggiunto ad ASA ¿ superiore ad ASA in
monoterapia nella riduzione del rischio di IM, ictus ischemico, mortalit¿ per
tutte le cause, ALI e amputazione maggiore di eziologia vascolare;
¿ valutare se rivaroxaban aggiunto ad ASA ¿ superiore ad ASA in
monoterapia nella riduzione del rischio di ospedalizzazione per disturbi
vascolari per un evento coronarico o periferico (su uno qualsiasi degli arti)
di natura trombotica;
¿ valutare se rivaroxaban aggiunto ad ASA ¿ superiore ad ASA in
monoterapia nella riduzione del rischio di IM, ictus per tutte le cause, morte
CV, ALI e amputazione maggiore di eziologia vascolare;

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Age =50, Documented moderate to severe symptomatic lower extremity peripheral artery occlusive disease, Technically successful peripheral infra-inguinal revascularization within the last 7 days prior to randomization

età =50, arteriopatia obliterante periferica sintomatica delle estremità inferiori da moderata a grave, rivascolarizzazione intra-inguinale avvenuta tecnicamente con successo negli ultimi 7 giorni prima della randomizzazione.

E.4

Principal exclusion criteria

Patients undergoing revascularization for asymptomatic peripherial
artery disease, mild
claudication without functional limitation or major tissue loss (including
severe ischemic ulcers or gangrene) of the index leg
- Patients undergoing revascularization of the index leg to treat an
asymptomatic or minimally symptomatic restenosis of a bypass graft or
target lesion restenosis
- Prior revascularization on the index leg within 8 weeks of the
qualifying revascularization
- Planned dual antiplatelet therapy use for the qualifying
revascularization procedure of clopidogrel in addition to Aspirin for >30
days after the qualifying revascularization procedure
- Planned dual antiplatelet therapy use for any other indication(s) with
any P2Y12 antagonists in addition to Aspirin after the qualifying
revascularization procedure

• pazienti sottoposti a rivascolarizzazione per PAD asintomatica, lieve
claudicazione senza limitazione funzionale o importante perdita di tessuti
(incluse gangrena o ulcere ischemiche gravi) della gamba indice;
• pazienti sottoposti a rivascolarizzazione della gamba indice per trattare una
restenosi asintomatica o minimamente sintomatica di un intervento di bypass
o restenosi della lesione target;
• precedente rivascolarizzazione sulla gamba indice entro 8 settimane dalla
rivascolarizzazione qualificante;
• uso di doppia terapia antipiastrinica (DAPT) pianificata per la procedura di rivascolarizzazione qualificante di clopidogrel in aggiunta ad ASA per > 30
giorni dopo la procedura di rivascolarizzazione qualificante;
• uso di DAPT pianificata per qualsiasi altra indicazione con qualsiasi
antagonista di P2Y12 in aggiunta ad ASA dopo la procedura di
rivascolarizzazione qualificante.

E.5 End points

E.5.1

Primary end point(s)

1. Time from randomization to the first occurrence of any of the
following major thrombotic vascular events: MI (Myocardial infarction),
ischemic stroke, CV (Cardiovascular) death, ALI (Acute limb ischemia),
and major amputation
2. Time from randomization to first occurrence of major bleeding events
according to the Thrombolysis in Myocardial Infarction (TIMI)
classification

La variabile dell’esito primario di efficacia sarà un endpoint composito consistente nel
tempo dalla randomizzazione alla prima occorrenza di uno qualsiasi dei seguenti
eventi vascolari trombotici maggiori: IM, ictus ischemico, morte CV, ALI e
amputazione maggiore dovuta a eziologia vascolare.
La variabile dell’esito primario di sicurezza sarà un endpoint consistente dalla randomizzazione all'occorenza del primo evento emorragico maggiore secondo la
classificazione di Trombolisi nell’infarto miocardico (TIMI).

E.5.1.1

Timepoint(s) of evaluation of this end point

Approximately 2 years

circa 2 anni

E.5.2

Secondary end point(s)

1. Time from randomization to first occurrence of an index limb
revascularization
2. Time from randomization to first occurrence of myocardial infarction,
ischemic stroke, coronary heart disease mortality, acute limb ischemia,
and major amputation of a vascular etiology
3. Time from randomization to first occurrence of myocardial infarction,
ischemic stroke, all-cause mortality,acute limb
ischemia, and major amputation of a vascular etiology
4. Time from randomization to first occurrence of hospitalization for a
coronary or peripheral cause (either lower limb) of a thrombotic nature
5. Time from randomization to first occurrence of myocardial infarction,
all-cause stroke, cardiovascular death, acute limb ischemia, and major amputation of a vascular etiology
6. Time from randomization to first occurrence of venous
thromboembolic (VTE) events
7. Time from randomization to all-cause mortality

Le variabili di efficacia secondarie dello studio saranno:
¿ tempo dalla randomizzazione alla prima occorrenza di una rivascolarizzazione
dell¿arto indice;
¿ tempo dalla randomizzazione alla prima occorrenza di IM, ictus ischemico,
mortalit¿ dovuta a coronaropatia, ALI e amputazione maggiore di eziologia
vascolare;
¿ tempo dalla randomizzazione alla prima occorrenza di IM, ictus ischemico,
mortalit¿ per tutte le cause, ALI e amputazione maggiore di eziologia vascolare;
¿ tempo dalla randomizzazione alla prima occorrenza di ospedalizzazione per una
causa coronarica o periferica (uno degli arti inferiori) di natura trombotica;
¿ tempo dalla randomizzazione alla prima occorrenza di IM, ictus per tutte le
cause, morte CV, ALI e amputazione maggiore di eziologia vascolare;
¿ tempo dalla randomizzazione alla prima occorrenza di eventi tromboembolici
venosi (VTE);
¿ tempo dalla randomizzazione alla prima occorrenza di mortalit¿ per tutte le
cause.

E.5.2.1

Timepoint(s) of evaluation of this end point

Approximately 2 years

Circa 2 anni

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

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)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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

Yes

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

234

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

Brazil

Canada

China

Korea, Democratic People's Republic of

Taiwan

Thailand

United States

Austria

Belgium

Bulgaria

Denmark

France

Germany

Hungary

Italy

Netherlands

Poland

Portugal

Romania

Spain

Sweden

Switzerland

United Kingdom

Czechia

Argentina

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.1.1.1

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:

2210

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

4290

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

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

560

F.4.2

For a multinational trial

F.4.2.1

In the EEA

3000

F.4.2.2

In the whole clinical trial

6500

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

Nessuno

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

2015-10-08

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-10-05

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2020-01-09

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