Clinical Trials Register

Summary
EudraCT Number:	2011-001094-58
Sponsor's Protocol Code Number:	BAY 59-7939 / 15572
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-05-23
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

Belgium - FPS Health-DGM

A.2

EudraCT number

2011-001094-58

A.3

Full title of the trial

Prospective, multi-center, randomized, heparin-controlled dose-finding trial to evaluate the efficacy and safety of rivaroxaban, a direct factor Xa inhibitor, on the background of standard dual antiplatelet therapy to support elective percutaneous coronary intervention (X-Plorer).

A.3.1

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

Exploring the efficacy and safety of rivaroxaban to support elective percutaneous coronary intervention.

A.3.2

Name or abbreviated title of the trial where available

X-plorer

A.4.1

Sponsor's protocol code number

BAY 59-7939 / 15572

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 HealthCare AG
B.1.3.4	Country	Germany
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.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	CTP Team /Ref:"EU CTR"/
B.5.3	Address:
B.5.3.1	Street Address	Bayer Schering Pharma AG, S102, Level 2, Room 156
B.5.3.2	Town/ city	Berlin
B.5.3.3	Post code	13342
B.5.3.4	Country	Germany
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	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	UnFractionated Heparin (UFH)
D.2.1.1.2	Name of the Marketing Authorisation holder	Any approved commercial source
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	Unfractionated heparin (UFH
D.3.2	Product code	Unfractionated heparin
D.3.4	Pharmaceutical form	Injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Heparin
D.3.9.1	CAS number	9005-49-6
D.3.9.3	Other descriptive name	HEPARIN
D.3.9.4	EV Substance Code	SUB02475MIG
D.3.10	Strength
D.3.10.1	Concentration unit	IU/kg international unit(s)/kilogram
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	50 to 100
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	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	No
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	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.3.9.4	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	10
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: 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	No
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	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.3.9.4	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	20
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

Symptomatic CAD patients due to undergo an elective (non emergent) Percutaneous Coronary Intervention (PCI) on one or two lesions in the native coronary vessel(s).

E.1.1.1

Medical condition in easily understood language

Narrowed coronary vessel requiring a Percutaneous Coronary Intervention.

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	13.1
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

The aim of this study is to assess whether rivaroxaban, as compared to unfractionated heparin, on the background of standard dual antiplatelet therapy (DAPT), can effectively suppress thrombosis, and related adverse ischemic events, upon balloon inflation and stent expansion, during elective PCI, without increasing bleeding.

E.2.2

Secondary objectives of the trial

To investigate the safety of rivaroxaban plus DAPT in the setting of elective PCI. Secondary objectives are safety criteria with respect to bleeding (TIMI major, TIMI monor and BARC type 2, 3 and 5) and the composite of clinical ischemic events (all death, non-fatal myocardial infarction [MI], non-fatal stroke and Target Lesion Revascularization [TLR]) be determined up to 30 days.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1) Male or female subject aged 18 years or more with no upper age limit and willing to comply with the protocol.
2) Symptomatic coronary artery disease due to undergo an elective (non- emergent) PCI on one or two lesions in the native coronary vessel(s). Cardiac standard troponin at baseline is within the normal limits.
3) Subject is able to read and give written informed consent and has signed an informed consent form approved by the Investigator's IRB/IEC after receiving detailed written and oral information prior to any study specific procedures.
4) Ability to understand and follow study-related instructions.

E.4

Principal exclusion criteria

1) Conditions that may increase the risk of the PCI procedure
o Lesion-specific conditions:
- Left main coronary artery disease
- Chronic Total Occlusions
- Bifurcation lesions involving a contiguous side branch with a
diameter bigger or equal to 2.5mm by visual estimate
- Three vessel disease requiring treatment of more than 2
lesions (no staging is allowed)

o Clinical condition at screening visit:
- ST-segment elevation myocardial infarction within 14 days
prior to randomization
- New York Heart Association class III or IV congestive heart
failure
- Hemodynamic instability
- Severe hypertension not adequately controlled by
antihypertensive therapy at the time of the study entry (BP
> 180/110mmHg)
2) Conditions that may increase the risk of bleeding, but are not limited to the following:
• Active internal bleeding
• Clinically significant gastrointestinal bleeding within 12
months before randomization
• History of intracranial, intraocular, spinal, or atraumatic
intraarticular bleeding
• History of hemorrhagic stroke
• Major surgery (including CABG), biopsy of a parenchymal
organ, ophthalmic surgery, or serious trauma (including
head trauma) within 30 days before randomization
• Known intracranial neoplasm, cerebral metastases,
arteriovenous malformation, or aneurysm at time of screening
• Known coagulopathy or bleeding diathesis (including
congenital bleeding disorders such as von Willebrand’s
disease or hemophilia; acquired bleeding disorders; and
unexplained clinically significant bleeding disorders)
• Platelet count <90.000/µl at screening visit
• Fibrinolytics within 10 days before randomization
• Any other condition known to increase the risk of bleeding
3. Concomitant conditions or diseases, such as:
• Significant valvular heart disease
• Calculated creatinine clearance ≤30 mL/min
• Known liver disease or high concentrations of ALT (> 3x the
upper limit of normal)
• Known allergy, hypersensitivity or contraindication to aspirin,
clopidogrel, heparin, rivaroxaban or contrast media
• Known HIV infection at time of screening
• Any other medical condition requiring systemic anticoagulation therapy
• Lactating/pregnant women
• Treatment with other investigational drugs or devices within 30 days before enrolment or planned use of investigational drugs or devices during the study
• Any condition that, in the opinion of the investigator, would compromise the well-being of the subject or the study or prevent the subject from meeting of performing study requirements
• Employees of the investigator or study center, with direct involvement in the proposed study or other studies under the direction of that investigator or study center, as well as family members of the employees or the investigator

4. Concomitant medication:
• Current use of anticoagulant drugs including VKA. factor IIa, of Factor Xa inhibitors.
• Systemic treatment with strong inhibitor or/and inducer of CYP3A4
• Chronic treatment with non-steroidal anti-inflammatory drugs (NSAIDs)
• Chronic treatment with aspirin > 100mg

E.5 End points

E.5.1

Primary end point(s)

The anticoagulant effect will be determined during the PCI procedure based on the number of subjects who:
- require bail-out anticoagulant therapy in the context of an ischemic coronary event and/or
- experience an angiographic flow limiting thrombotic event (i.e. abrupt vessel closure, visible thrombus, no-reflow) and/or
- experience thrombus formation on the PCI equipment (i.e. guiding catheter and guidewire thrombus) and/or
- experience an Myocardial Infarction (MI) due to the PCI procedure (i.e. procedural MI)

E.5.1.1

Timepoint(s) of evaluation of this end point

Day 1 (the day of the PCI procedure).

E.5.2

Secondary end point(s)

Efficacy variables:
- Separate components of the primary endpoint
- Clinical ischemic events up to 30 days after index PCI assessed by the compositeendpoint of:
o All death
o Non-fatal myocardial infarction (excluding those events due to
the procedure alone and reported as primary endpoint)
o Stroke
o Clinically indicated TLR
- The incidence of clinically indicated TLR up to 30 days after index PCI
- Definite and probable stent thrombosis up to 30 days after index PCI according to theAcademic Research Consortium (ARC) definition

Safety variables:
- Bleeding events up to 30 days post index PCI procedure:
o Incidence of clinically significant bleeding according to:
- TIMI major
- TIMI minor
- Requiring medical attention
o Incidence of bleeding according to BARC type 2, 3 and 5
- Any other SAEs up to 30 days post index PCI procedure.

E.5.2.1

Timepoint(s) of evaluation of this end point

till 30 days + 7 days.

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

Yes

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

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

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Semi-blind: 4 arms of which 2 non-blind (comparator and comparator+IMP) and 2 blind (IMP in 2 doses)

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

Yes

E.8.2.3.1

Comparator description

UnFractionated Heparin (UFH)

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

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

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

F.4.2

For a multinational trial

F.4.2.1

In the EEA

105

F.4.2.2

In the whole clinical trial

105

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)

standard care for PCI patients according hospital practice.

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

2011-06-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-09-13

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-03-04

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