Clinical Trials Register

Summary
EudraCT Number:	2010-024485-21
Sponsor's Protocol Code Number:	daisy
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:	2013-01-15
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

2010-024485-21

A.3

Full title of the trial

Dipyridamole versus Adenosine infusion in the physiologic assessment of Intermediate coronary Stenoses in the cardiac catheterization laboratorY

Infusione di dipiridamolo contro adenosina nella valutazione della rilevanza fisiologica di stenosi coronariche intermedie nel laboratorio di emodinamica

A.3.1

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

Comparison between Dipyridamole and Adenosine infusion in the evaluation of intermediate coronary restrictions (stenoses) in the cardiac catheterization laboratorY.

Confronto tra infusione di dipiridamolo e adenosina nella valutazione dei restringimenti (stenosi) intermedi a livello delle arterie coronarie nel laboratorio di emodinamica.

A.3.2

Name or abbreviated title of the trial where available

DAISY

A.4.1

Sponsor's protocol code number

daisy

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	FONDAZIONE TOSCANA GABRIELE MONASTERIO
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	FONDAZIONE TOSCANA GABRIELE MONASTERIO
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	FONDAZIONE TOSCANA GABRIELE MONASTERIO
B.5.2	Functional name of contact point	U.O. EMODINAMICA
B.5.3	Address:
B.5.3.1	Street Address	via Aurelia Sud
B.5.3.2	Town/ city	Massa
B.5.3.3	Post code	54100
B.5.3.4	Country	Italy
B.5.4	Telephone number	0585-493507
B.5.5	Fax number	0585-493508
B.5.6	E-mail	marco.vaghetti@ftgm.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	PERSANTIN*IV 10F 10MG/2ML
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.3.4	Pharmaceutical form	Solution for 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	DIPYRIDAMOLE
D.3.9.1	CAS number	58-32-2
D.3.9.4	EV Substance Code	SUB07229MIG
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: 2
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	ADENOSCAN*INF 6F 30MG 10ML
D.2.1.1.2	Name of the Marketing Authorisation holder	SANOFI-AVENTIS SpA
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.3.4	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	ADENOSINE
D.3.9.1	CAS number	58-61-7
D.3.9.4	EV Substance Code	SUB00297MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	30
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

Patients with a single ≥ 50% e <75% coronary stenosis (visually extimated) at angiography, in one ore more coronary vessels).

Pazienti con una singola stenosi evidenziata alla coronarografia ≥ 50% e <75% ad una stima visiva, in uno o più vasi coronarici.

E.1.1.1

Medical condition in easily understood language

Patients with a single restriction (stenosis) ≥ 50% e <75% of coronary arteries, visually extimated during angiography, in one ore more coronary vessels.

Pazienti con un singolo restringimento (stenosi) delle arterie coronarie ≥ 50% e <75% del diametro del vaso in uno o più vasi coronarici, valutato visivamente durante la coronarografia.

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

MedDRA Classification

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 main objective of the study is to assess the feasibility of dipyridamole as hyperaemia inducing agent in the Fractional Flow Reserve (FFR) assessment.

L'obiettivo principale dello studio è di dimostrare la possibilità di utilizzo del dipiridamolo come farmaco inducente iperemia massimale nella misurazione della riserva di flusso frazionale (FFR).

E.2.2

Secondary objectives of the trial

To evaluate the tolerability of dypiridamole as hyperaemia inducing agent in the measurement of FFR.

Testare la tollerabilità dell’infusione endovenosa periferica di dipiridamolo come agente inducente iperemia massimale nella misurazione della FFR.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patients of any race, male or female gender, with a single ≥ 50% e <75% coronary stenosis (visually extimated) at angiography, in one ore more coronary vessels. Age ≥ 18 years. Patients should sign an informed consent prior to the enrollment in the study.

Pazienti di qualsiasi razza, sesso maschile o femminile che presentino una o più stenosi ≥ 50% e <75% ad una stima visiva in uno o più vasi coronarici. Età superiore a 18 anni. I pazienti dovranno aver firmato consenso informato scritto di partecipazione allo studio.

E.4

Principal exclusion criteria

Known intolerance of adenosine and/or dypiridamol and/or teophylline or of the eccipients. Patients who have taken caffein or food or beverages containig caffein and/or similar substances 24 hours before the procedure. Left main or aorto-ostial lesions. Lesions in severely tortuous or calcific vessels. Severely impaired left ventricular function (EF<35%). Chronic obstructive bronchopneumopathy or bronchial asthma Atrio-ventricular block >I°. Stenosis >70% of supra-aortic vessels. Concomitant treatment with teophylline-derivatives. Concomitant therapy with phosphodiesterase inhibitors derivatives. Hypotension (PASys <100 mmHg). Atrial fibrillation. Pregnant or lactating women. Pazients with a lesion in a culprit coronary vessel in patients with prior or recent myocardial infarction. Pazients with ST-elevation myocardial infarction ≤5 days (lesion in non-culprit vessel).

Intolleranza nota ad adenosina e/o dipiridamolo e/o teofillina o agli eccipienti. Pazienti che abbiano assunto caffeina e analoghe sostanze o alimenti e/o bevande contenenti caffeina e/o analoghi ≤24 ore prima della procedura. Lesioni del tronco comune della coronaria sinistra o lesioni aorto-ostiali. Lesioni in segmenti estremamente tortuosi e/o calcifici. Compromissione grave della funzione ventricolare sinistra (EF<35%). Broncopneumopatia cronica ostruttiva o asma bronchiale. Blocco atrio-ventricolare di grado >I° Stenosi significativa (>70%) dei tronchi sovra-aortici. Trattamento con farmaci a base di teofillina. Terapia con farmaci inibitori delle fosfodiesterasi. Ipotensione (PAS <100 mmHg). Fibrillazione atriale. Donne in stato di gravidanza o allattamento. Pazienti con lesione in arteria/e responsabile/i di recente o pregresso infarto miocardico. Pazienti con infarto miocardico con sopraslivellamento ST ≤5 giorni (se lesione su vaso non responsabile di infarto).

E.5 End points

E.5.1

Primary end point(s)

To show non inferior diagnostic accuracy of a FFR assessment with dipyridamole, infused in a peripheral vein, as pharmacological agent inducing maximal hyperaemia , compared to a continuous adenosine infusion in a central vein, considered as the “gold standard”. The diagnostic accuracy will be measured with ROC curves analysis.

Dimostrare una non inferiore accuratezza diagnostica di una misurazione della FFR utilizzando come farmaco inducente iperemia massimale il dipiridamolo, infuso in via endovenosa periferica, rispetto alla adenosina infusa in via venosa centrale, considerata come “gold standard”. La accuratezza diagnostica verrà misurata mediante analisi delle curve ROC.

E.5.1.1

Timepoint(s) of evaluation of this end point

12 months

12 mesi

E.5.2

Secondary end point(s)

To evaluate a better tolerability and a reduction of side effects with dipyridamole, compared to adenosine infusion, with a tolerability test for each drug.

Dimostrare la migliore tollerabilità dell’infusione endovenosa periferica di dipiridamolo, rispetto all’infusione endovenosa sistemica di adenosina mediante un questionario di tollerabilità per entrambi i farmaci.

E.5.2.1

Timepoint(s) of evaluation of this end point

12 months

12 mesi

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

Yes

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

Yes

E.6.13.1

Other scope of the trial description

Tolerability

Tollerabilità

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

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

Yes

E.8.1.7.1

Other trial design description

tutti i pazienti sottoposti ad entrambi i trattamenti

all patient will receive both treatments

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

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

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

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

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:

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

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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

F.4.2.2

In the whole clinical trial

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)

At the end of the study, all the patients enrolled will be treated as other patients non included in the present study.

Al termine dello studio i pazienti arruolati saranno trattati in maniera del tutto confrontabile con i pazienti che non parteciperanno allo studio.

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

2013-04-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-01-17

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

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