Clinical Trials Register

Summary
EudraCT Number:	2009-015013-46
Sponsor's Protocol Code Number:	AnaesthesiaResearch024
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:	2012-09-21
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

2009-015013-46

A.3

Full title of the trial

Aspirin and Tranexamic Acid for Coronary Artery Surgery Trial

ATACAS (ASA e acido tranexamico nell'intervento di by-pass aorto coronarico CABG)

A.3.1

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

Aspirin and Tranexamic Acid for Coronary Artery Surgery Trial

ATACAS (ASA e acido tranexamico nell'intervento di by-pass aorto coronarico CABG)

A.3.2

Name or abbreviated title of the trial where available

ATACAS

A.4.1

Sponsor's protocol code number

AnaesthesiaResearch024

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	ALFRED HEALTH
B.1.3.4	Country	Australia
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	Alfred Health
B.4.2	Country	Australia
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Fondazione Centro San Raffaele del Monte Tabor
B.5.2	Functional name of contact point	Anestesia e Rianimazione
B.5.3	Address:
B.5.3.1	Street Address	Via Olgettina, 58
B.5.3.2	Town/ city	Milano
B.5.3.3	Post code	20132
B.5.3.4	Country	Italy
B.5.4	Telephone number	0390226436155
B.5.5	Fax number	0390226436152
B.5.6	E-mail	zuppelli.paola@hsr.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	Aspirin protect 100 mg
D.2.1.1.2	Name of the Marketing Authorisation holder	Bayer Vital GmBh
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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.3.4	Pharmaceutical form	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.3.9.3	Other descriptive name	aspirin
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	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	Yes
D.2.1.1.1	Trade name	Cyklokapron
D.2.1.1.2	Name of the Marketing Authorisation holder	Pharmacia limited
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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.3.4	Pharmaceutical form	Infusion
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	TRANEXAMIC ACID
D.3.9.1	CAS number	1197-18-8
D.3.9.4	EV Substance Code	SUB11214MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/kg milligram(s)/kilogram
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	50
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	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	Infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Coronary Artery Bypass Grafting

by-pass aortocoronarico

E.1.1.1

Medical condition in easily understood language

coronary revascularization

rivascolarizzazione chirurgica delle coronarie

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	15.0
E.1.2	Level	SOC
E.1.2	Classification code	10007541
E.1.2	Term	Cardiac disorders
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

This prospective, randomised, double-blind, factorial trial will test whether aspirin,
tranexamic acid, or both, can reduce mortality and/or major morbidity after elective coronary
artery surgery.
We propose a large randomised controlled trial to answer two clinically important questions:
i. Should low-dose aspirin be continued up until the day of CABG surgery?
ii. Should TxA be used for all at-risk CABG surgery?

Scopo dello studio è verificare se ASA e/o acido tranexamico, somministrati nel perioperatorio di pazienti sottoposti a CABG in elezione, siano in grado di ridurre la mortalità e/o le più gravi complicanze postoperatorie.
L’obiettivo principale è un endpoint composito di mortalità a 30 giorni e/o complicanze maggiori (IMA, ictus cerebri, tromboembolia polmonare, insufficienza renale ed infarto intestinale).

E.2.2

Secondary objectives of the trial

(i) 30-day mortality
(ii) Ischaemic complications
· Myocardial infarction
· Stroke
· Renal failure
· Pulmonary embolism
· Bowel infarction
(iii) Bleeding complications
· Major haemorrhage (re-operation for bleeding)
· Cardiac tamponade
· Number of transfused blood product units

(i) mortalità a 30 giorni
(ii) Complicanze ischemiche
· infarto del miocardio
· Ictus
· insufficienza renale
· embolia polmonare
· infarto intestinale
(iii) Complicanze emorragiche
· sanguinamenti maggiori (re-intervento per sangionamento)
· tamponamento cardiaco
· Numbero di trasfusioni

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Males and females, age 18 years and over
2. Written, informed consent
3. Elective coronary artery surgery (on-pump or off-pump)
4. Patient is at increased risk of major complications, defined by any of:
· Age ³70 years
· Left ventricular impairment (fractional area change <20%, ejection fraction
<40%, or at least moderate impairment on ventriculography)
· Concomitant valvular or aortic surgery
· Aneurysmectomy
· Repeat cardiac surgery (“re-do”)
· Chronic obstructive pulmonary disease
· Renal impairment (se. creatinine >150 mmol/l or creatinine clearance <45
ml/min)
· Obesity (body mass index >25 kg/m2)
· Pulmonary hypertension (mPAP >25 mmHg)
· Peripheral vascular disease.

I criteri di inclusione sono:
• età>18 anni;
• firma del consenso informato;
• pazienti ad alto rischio di complicanze, definite come almeno una delle seguenti:
• età>70 anni;
• disfunzione ventricolare sinistra (frazione d’eiezione<40%);
• concomitante chirurgia valvolare o aortica;
• aneurismectomia del ventricolo sinistro;
• pregresso intervento cardiochirurgico;
• bronco pneumopatia cronica ostruttiva;
• insufficienza renale cronica (creatinina clearance< 45 ml/min);
• obesità (BMI>25 kg/mq);
• ipertensione polmonare (mPAP> 25 mmHg);
• vasculopatia periferica.

E.4

Principal exclusion criteria

1. Poor (English) language comprehension
2. Clinician preference for antifibrinolytic therapy
3. Urgent surgery for unstable coronary syndromes where for clinical reasons
antiplatelet medication cannot be discontinued
4. Active peptic ulceration
5. Allergy or contraindication to aspirin or tranexamic acid
6. Aspirin therapy within 4 days of surgery
7. Warfarin or clopidogrel therapy within 7 days of surgery, or GIIb/IIIa antagonists
within 24 h of surgery
8. Thrombocytopaenia or any other known history of bleeding disorder
9. Severe renal impairment (serum creatinine >250 mmol/l, or estimated creatinine
clearance <25 ml/min)
10. Recent haematuria
11. Thromboembolic disease relating to: history of postoperative or spontaneous
pulmonary embolism, spontaneous arterial thrombosis or familial hypercoaguability
(eg. Lupus anticoagulant, protein C deficiency)
12. Pregnancy.

I criteri di esclusione sono:
• scarsa comprensione della lingua italiana;
• preferenza dei curanti per una terapia antifibrinolitica;
• CABG in urgenza per sindrome coronaria acuta, con impossibilità a sospendere prima dell’intervento la terapia antiaggregante;
• ulcera peptica attiva;
• allergia o controindicazioni alla terapia con acido acetilsalicilico (ASA) o acido tranexamico;
• terapia con ASA nei 4 giorni precedenti l’intervento;
• terapia con warfarin o clopidogrel nei 7 giorni precedenti l’intervento;
• terapia con antagonisti GIIb/IIIa nelle 24 ore precedenti l’intervento;
• trombocitopenia o qualsiasi altro disordine dell’emostasi;
• grave insufficienza renale (creatinina clearance<25 ml/min)
• recente ematuria;
• gravidanza;
• malattia tromboembolica (storia di tromboembolia polmonare spontanea o postoperatoria, trombosi arteriosa spontanea o disordini ereditari protrombotici)

E.5 End points

E.5.1

Primary end point(s)

A composite endpoint including 30-day mortality or major ischaemic morbidity (myocardial
infarction, stroke, pulmonary embolism, renal failure, bowel infarction)

Un endpoint composito di mortalità a 30 giorni e/o complicanze maggiori (IMA, ictus cerebri, tromboembolia polmonare, insufficienza renale ed infarto intestinale)

E.5.1.1

Timepoint(s) of evaluation of this end point

at 30 days following surgery

fino a 30 giorni dopo l'intervento

E.5.2

Secondary end point(s)

Secondary Endpoints
(i) 30-day mortality
(ii) Ischaemic complications
· Myocardial infarction
· Stroke
· Renal failure
· Pulmonary embolism
· Bowel infarction
(iii) Bleeding complications
· Major haemorrhage (re-operation for bleeding)
· Cardiac tamponade
· Number of transfused blood product units

E.5.2.1

Timepoint(s) of evaluation of this end point

at 30 days following surgery

a 30 giorni

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

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)

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

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

disegno fattoriale

2 X 2 FACTORIAL DESIGN

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

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

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

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

Hong Kong

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

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:

3600

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

1000

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

1000

F.4.2

For a multinational trial

F.4.2.1

In the EEA

1500

F.4.2.2

In the whole clinical trial

4600

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)

as per usual 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

2012-11-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-09-13

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

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