Clinical Trials Register

Summary
EudraCT Number:	2012-001260-29
Sponsor's Protocol Code Number:	2012-CARDAF
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:	2012-03-29
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

2012-001260-29

A.3

Full title of the trial

Identification of predictive plasma Biomarkers and use of a high dosage statin during a procedure of Parrossistic Atrial Fibrillation pharmacological Cardioversion

Identificazione di biomarcatori umorali predittivi e utilizzo di una somministrazione di una statina ad alto dosaggio in corso di cardioversione farmacologica nella Fibrillazione atriale parossistica.

A.3.1

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

Identification of predictive plasma Biomarkers and use of a high dosage statin during a procedure of Parrossistic Atrial Fibrillation Cardioversion

A.3.2

Name or abbreviated title of the trial where available

2012-CARDAF

A.4.1

Sponsor's protocol code number

2012-CARDAF

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 ISTITUTO SAN RAFFAELE-G.GIGLIO
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 Istituto San Raffaele G. Giglio di Cefalu'
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 Istituto San Raffaele G. Giglio di Cefalu'
B.5.2	Functional name of contact point	Clinical Trial Office
B.5.3	Address:
B.5.3.1	Street Address	C.da Pietrapollastra
B.5.3.2	Town/ city	Cefalu'
B.5.3.3	Post code	90015
B.5.3.4	Country	Italy
B.5.4	Telephone number	0921920381
B.5.5	Fax number	0921920510
B.5.6	E-mail	alessandra.danna@hsrgiglio.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.2.1.2	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	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	ATORVASTATIN CALCIUM
D.3.9.1	CAS number	134523-03-8
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	NA
D.3.9.4	EV Substance Code	SUB12958MIG
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	80
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Parossistic Atrial Fibrillation according to the European Socierty of Cardiology (ESC)criteria

Fibrillazione atriale parossistica definita secondo i criteri della European Socierty of Cardiology (ESC)

E.1.1.1

Medical condition in easily understood language

recently diagnosed Atrial Fibrillation characterized by recurrent episodes

fibrillazione atriale di recente insorgenza, che abbia caratteri di episodicità

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	14.1
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

1)the chance of a plasma biomarker to predict a successful pharmacological cardioversion. 2)The chance of a plasma biomarker to predict a reduction of the pharmacological cardioversion time 3) the chance that a single dose of rosuvatatin 40 mg might increase the successful pharmacological cardioversion rate 4) the chance that a single dose of rosuvatatin 40 mg might reduce of the pharmacological cardioversion time

Valutare: 1)la possibilità che un biomarcatore plasmatico possa essere predittivo di una cardioversione farmacologica favorevole 2)la possibilità che un biomarcatore plasmatico possa essere predittivo di una riduzione del tempo di cardioversione farmacologica 3)la possibilità che la somministrazione di una singola dose di rosuvastatina 40 mg possa aumentare le probabilità di una cardioversione favorevole 4)la possibilità che la somministrazione di una singola dose di rosuvastatina 40 mg possa ridurre i tempi di cardioversione

E.2.2

Secondary objectives of the trial

1) the chance of a biomarker to predict the probability to maintain a sinus heart rhythm after 1 year since the pharmacological cardioversion. 1) the chance that a single dose of rosuvatatin 40 mg might increase the probability to maintain a sinus heart rhythm after 1 year since the pharmacological cardioversion.

1)la possibilità che un biomarcatore plasmatico possa essere predittivo della probabilità di mantenere il ritmo sinusale a 1 anno dalla cardioversione farmacologica 2)la possibilità che la somministrazione di una singola dose di rosuvastatina 40 mg possa aumentare della probabilità di mantenere il ritmo sinusale a 1 anno dalla cardioversione

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1) patient between 18 and 75 years of age 2) patient able to understand the study aims and methods, to sign the informed consents relative to the part of the study he is willing to participate 3) patient showing the medical conditions that make a cardioversion procedure mandatory 4) patient whose clinical conditions allow to delay the cardioversion procedure for the time required to enroll the patients in the study (stable patient, that is not feeling extreme pain or anxiety for the condition related to the current episode of atrial fibrillation)

1)età compresa tra i 10 e i 75 anni 2) paziente in grado di comprendere le finalità e le modalità dello studio , e di acconsentire alla firma dei consensi informati relativi alla fase dello studio a cui intende partecipare 3) sussistenza del le condizioni mediche che rendano opportuna l’inizio della procedura farmacologica 4) sussistenza dei tempi tecnici necessari allo svolgimento delle fasi dello studio , cioè che il breve tempo necessario alla proposta dello studio in questione non pregiudichi le condizioni di salute del paziente (pz emodinamicamente stabile, che non manifesti una condizione di urgenza o di sofferenza per le considioni legate all episodio di FA)

E.4

Principal exclusion criteria

1) hemodynamically unstable patient or bearing comorbidities precluding the possibility to complete the procedures of the study. 2) patient with diagnosis of class III-IV heart failure according to the NYHA classification 3) patients assuming chronically a statin at maximum dosage. 4) patient without hystory of statin intollerance characterized by: statin related myalgia and/or increase of specific enzymes elevation (CK > 2xULN; AST or ALT > 3x ULN) 5) patient assuming oral anticoagulant therapy 6) patient with affections determining intestinal malabsorption as: gastro-ileal by pass, gastric banding, other causes 7) patient with chronic kidney disease stage IV or more according to the NFK classification (calculated Glomerular filtrate rate < 30 ml/min) 8) patient with altered consciousness level, and/or a mental disease not adequately controlled by drug therapy.

1) paziente non emodinamicamente stabile o con comorbidità tali da non consentire lo sviluppo delle fasi dello studio in questione 2) paziente in scompenso cardiaco classe III-IV NYHA 3) paziente che assume in cronico dosaggio massimale di terapia con statine 4) paziente che non riferisca episodi di intolleranze pregresse alle statine caratterizzate da : mialgie in concomitanza all’ uso delle statine e/o riferito aumento dei valori di CPK > 2 x ULN, AST or ALT > 3x ULN). 5) paziente in terapia con anticoagulanti orali 6) paziente con condizioni note di malassorbimento quali: bypass ileale, bendaggio gastrico o altre cause 7) paziente in insufficienza renale nota classe IV o più secondo la classificazione NFK (con filtrato glomerulare stimato inferiore a 30 ml/min) 8) paziente con stato mentale alterato, e/o con diagnosi di patologia psichiatrica non adeguatamente controllata dalla terapia corrente.

E.5 End points

E.5.1

Primary end point(s)

1) successful pharmacological cardioversion rate (number of subjects that recovered their sinus rhythm after the cardioversion procedure / number of subjects subjected to the procedure) 2) the time occurred to recover the normal sinus heart rhythm during a pharmacological cardioversion procedure (the interval time between the start of the procedure and time in which the sinus rhythm is virtually recovered)

1) la proporzione di cardioversione farmacologica favorevole (numero dei soggetti che hanno ottenuto un ripristino de ritmo sinusale dopo cardioversione farmacologica / numero dei soggetti che hanno intrapreso la procedura di cardioversione) 2) il tempo necessario al ripristino del ritmo sinusale in corso di cardioversione farmacologica (tempo intercorso tra l'inizio della procedura di cardioversione ed il tempo in cui avviene il ripristino del ritmo sinusale)

E.5.1.1

Timepoint(s) of evaluation of this end point

This end point will be collected in the time interval required to consider the procedure unsuccessful according to the standard clinical procedures, so that the physican is allowed to proceed to alternative protocols (electrical cardioversion, other). This interval is set to 24 hours

L'end point potrà essere rilevato entro il tempo in cui attraverso la comune pratica clinica si dichiara la procedura fallita e si può eventualmente procedere a protocolli terapeutici alternativi. (cardioversione elettrica, altro). Questo intervallo di tempo è quantificato in 24 ore.

E.5.2

Secondary end point(s)

proportion of patients that are still maintaining their sinus hearth rhythm after: i) 6 months since the pharmacological cardioversion procedure ii) 12 months since the pharmacological cardioversion procedure

proporzione di soggetti che mantengono il ritmo sinusale i) nei 6 mesi successivi alla cardioversione. ii) nei 12 mesi successivi alla cardioversione.

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

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)

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

E.8.1.3

Single blind

Yes

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

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

Yes

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

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:

120

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

120

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

Yes

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

Yes

F.3.3.4

Nursing women

Yes

F.3.3.5

Emergency situation

Yes

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

patient with altered consciousness level, and/or a mental disease not adequately controlled by drug therapy

Soggetti con stato mentale alterato con diagnosi di patologia psichiatrica non adeguatamente controllata dalla terapia corrente.

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

240

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 medical treatment

Trattamento medico standard

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

2012-04-24

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-03-15

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

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