Clinical Trials Register

Summary
EudraCT Number:	2011-002876-18
Sponsor's Protocol Code Number:	2011-002876-18
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:	2011-09-06
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

2011-002876-18

A.3

Full title of the trial

CYCLosporinE A in reperfused acute myocardial infarction (CYCLE-Trial)

Ciclosporina A nell'infarto miocardico acuto riperfuso (studio CYCLE)

A.3.1

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

A phase III study to determine whether Cyclosporine A improves outcomes after successful primary angioplasty, by improving myocardial reperfusion.

Studio di fase III per verificare se Ciclosporina A puo' migliorare l'esito di un infarto miocardico acuto riperfuso con successo mediante angioplastica primaria, favorendo la riperfusione miocardica.

A.3.2

Name or abbreviated title of the trial where available

CYCLE

A.4.1

Sponsor's protocol code number

2011-002876-18

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	IST. DI RICERCHE FARMACOLOG. M. NEGRI
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 per il Tuo cuore ONLUS: premio ANMCO 2010
B.4.2	Country	Italy
B.4.1	Name of organisation providing support	Novartis Italia
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	ISTITUTO DI RICERCHE FARMACOLOGICHE MARIO NEGRI
B.5.2	Functional name of contact point	DIP. RICERCA CARDIOVASCOLARE
B.5.3	Address:
B.5.3.1	Street Address	VIA LA MASA 19
B.5.3.2	Town/ city	MILANO
B.5.3.3	Post code	20156
B.5.3.4	Country	Italy
B.5.4	Telephone number	02-02-39014454
B.5.5	Fax number	02-33200049
B.5.6	E-mail	cycle@marionegri.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	SANDIMMUN*INFUS10F 5ML 50MG/ML
D.2.1.1.2	Name of the Marketing Authorisation holder	NOVARTIS FARMA 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	Solution for 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	CICLOSPORIN
D.3.9.1	CAS number	59865-13-3
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	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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

All (male and female) patients, aged over 18, presenting with a large STEMI not older than 4 hours (defined as angina pectoris or equivalent symptoms of more than 30 minutes duration within the last 4 hours and a sum of ST-elevation > 4mm), with a TIMI-flow 0 or 1 in the identified culprit artery, for whom the clinical decision was made to treat with percutaneous coronary intervention (PCI) are eligible for the study.

E.1.1.1

Medical condition in easily understood language

Patients admitted within 4 hours of symptom onset of acute myocardial infarction with ST segment elevation, candidates for primary angioplasty.

Pazienti ricoverati entro 4 ore dall'inizio dei sintomi di infarto miocardico acuto, con slivellamento del tratto ST, candidati per angioplastica primaria.

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	14.0
E.1.2	Level	LLT
E.1.2	Classification code	10064345
E.1.2	Term	ST segment elevation myocardial infarction
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 primary objective of the present study is improvement of myocardial reperfusion, measured with ST-segment resolution >=70% 1 hour after PCI.

Obiettivo primario di questo studio è il miglioramento della riperfusione miocardica, valutata con la risoluzione del tratto ST>=70% 1 ora dopo PCI.

E.2.2

Secondary objectives of the trial

High sesnsitive troponin T (hsTnT) at day 4 after PCI. All-cause mortality, HF or shock within 6 months of randomization; re-hospitalization for CV reasons within 6 months of randomization.

Troponina-T ad alta sensibilità (hsTnT) in 4a giornata dopo PCI, mortalità totale, insufficienza cardiaca sintomatica o shock cardiogeno o riospedalizzazione per ragioni cardiovascolari nei 6 mesi seguenti la randomizzazione.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

All (male and female) patients, aged over 18, presenting with a large STEMI within 4 hours of onset (defined as angina pectoris or equivalent symptoms of more than 20 minutes duration within the last 4 hours and ST elevation in ≥ 3 leads in anterior MI and/or a deviation in ≥ 4 leads in inferior MI, with a TIMI-flow 0 or 1 in the culprit artery, committed to treatment with PCI) are eligible for the study. Patients will only be included if they are able to understand the nature, scope, and possible consequences of study participation, and written informed consent will be sought.

Pazienti di entrambi i sessi, >=18 anni, con uno STEMI esteso (definito come angina pectoris o sintomi equivalenti da più di 20 minuti, nelle prime 4 ore dall’inizio dei sintomi e un sopraslivellamento del tratto ST in almeno 3 derivazioni in sede anteriore e/o una deviazione in almeno 4 derivazioni in sede inferiore, associato a un flusso TIMI 0 o 1 nella coronaria colpevole dello STEMI), con indicazione alla angioplastica primaria (PCI).I pazienti saranno arruolati solo se in grado di comprendere la natura, lo scopo e le possibili conseguenze legate alla loro partecipazione allo studio; verrà richiesta la firma di consenso informato.

E.4

Principal exclusion criteria

Left bundle branch block; TIMI-flow >1 in the identified culprit artery; current (≤ 10 days) treatment with CsA or contraindication regarding treatment with CsA; coronary anatomy not suitable for PCI; thrombolytic therapy within 24 hrs. before randomization; previous myocardial infarction; previous CABG; severe renal or hepatic insufficiency; malignant tumor, not curatively treated; women with childbearing potential, esp. pregnant or nursing women; participation in another clinical or device trial within the previous 30 days.

blocco di branca sinistra; flusso TIMI>1 nella coronaria colpevole; terapia con CsA entro i 10 giorni precedenti la randomizzazione o controindicazioni alla CsA; anatomia coronarica inadatta a PCI; terapia trombolitica nelle 24 ore precendenti la randomizzazione; IMA pregresso; CABG pregresso; insufficienza renale o epatica grave; tumore maligno, non curabile; donna in età fertile, specie se gravida o in allattamento; partecipazione ad un altro trial clinico negli ultimi 30 giorni.

E.5 End points

E.5.1

Primary end point(s)

Improvement of myocardial reperfusion, measured with ST-segment resolution >=70%

miglioramento della riperfusione miocardica, valutata con la risoluzione del tratto ST>=70%

E.5.1.1

Timepoint(s) of evaluation of this end point

1 hour after PCI.

1 ora dopo PCI.

E.5.2

Secondary end point(s)

Troponin (hsTnT) at day 4 after PCI, all-cause mortality, HF or shock within 6 months of randomization; re-hospitalization for CV reasons.

Troponina (hsTnT) in 4a giornata dopo PCI, mortalità totale, insufficienza cardiaca sintomatica o shock cardiogeno o riospedalizzazione per ragioni cardiovascolari nei 6 mesi seguenti la randomizzazione.

E.5.2.1

Timepoint(s) of evaluation of this end point

Troponin T: 4 hours; Echocardiography: pre-discharge and 6 months

Troponina T: 4 ore; Ecocardiografia: pre-dimissione e 6 mesi

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)

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

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

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

non trattati con ciclosporina A

untreated with ciclosporin A

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

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:

264

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

180

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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2011-09-06.

Yes

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

Yes

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

patients early after myocardial infarction with chest pain under stress

soggetti infartuati recenti con dolore precordiale in condizioni di stress

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

444

F.4.2

For a multinational trial

F.4.2.1

In the EEA

444

F.4.2.2

In the whole clinical trial

444

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
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	Fondazione per il Tuo cuore ONLUS
G.4.3.4	Network Country	Italy

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2011-12-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-07-27

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-11-17

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