Clinical Trials Register

Summary
EudraCT Number:	2012-000232-25
Sponsor's Protocol Code Number:	P110138
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-08-27
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

France - ANSM

A.2

EudraCT number

2012-000232-25

A.3

Full title of the trial

Efficacité du prétraitement par levosimendan avant pontage aorto-coronaire sous circulation extra-corporelle chez des patients à haut risque (FE < 40%): essai randomisé, multicentrique, en double insu versus placebo. LICORN: Levosimendan In COronary RevascularisatioN

A.3.2

Name or abbreviated title of the trial where available

LICORN

A.4.1

Sponsor's protocol code number

P110138

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	ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)
B.1.3.4	Country	France
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	simdax
D.2.1.2	Country which granted the Marketing Authorisation	Finland
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	Simdax
D.3.4	Pharmaceutical form	Concentrate for 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	levosimendan
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	2.5
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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	Concentrate for solution for 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

patients avec FEVG 40% et devant bénéficier d'une chirurgie coronaire avec CEC, seule ou combinée à une chirurgie valvulaire

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.1
E.1.2	Level	LLT
E.1.2	Classification code	10068176
E.1.2	Term	Coronary artery bypass graft
E.1.2	System Organ Class	100000004865

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

L'objectif principal est d'évaluer l'efficacité du prétraitement par levosimendan au moment de l'induction anesthésique chez des patients dont la FEVG est 40% et devant bénéficier d'une chirurgie cardiaque sous CEC de type PAC (avec ou sans chirurgie valvulaire) pour réduire l'incidence et la sévérité du SBDC postopératoire.

E.2.2

Secondary objectives of the trial

- comparer le taux de mortalité à J 28 et J 180 pour les patients des 2 groupes.
- évaluer l'impact économique de l'injection du levosimendan selon une étude de type " coût-efficacité " pendant le séjour hospitalier

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- patient d'âge 18 ans
- patient bénéficiant d'un régime de sécurité sociale
- patient ayant reçu et compris l'information et, ayant signé le consentement éclairé
- patients devant subir un PAC seul ou associé à une chirurgie valvulaire avec CEC
- FEVG préopératoire 40% (documentée par un examen de moins de 6 mois)
- Les patients présentant une insuffisance circulatoire aiguë préopératoire sous traitement inotrope positif et/ou assistance mécanique (BCPIA ou ECLS) peuvent être inclus dans l'étude. Le traitement par levosimendan ou placebo se surajoutant au traitement existant. La technique de minimisation est prévue pour équilibrer la distribution de tels patients entre les 2 groupes.

E.4

Principal exclusion criteria

- patient ayant refusé de donner son consentement
- PAC sans CEC
- chirurgie valvulaire sans geste de revascularisation coronaire sous CEC associé
- femme enceinte ou en cours d'allaitement
- participation du patient à un autre protocole de recherche clinique.
- Contre-indications au levosimendan (celles de la monographie) : (allergie connue au levosimendan ou à l'un de ses excipients , insuffisance rénale sévère préopératoire (clairance de la créatinine <30 mL/min) , patient nécessitant des séances de dialyse en préopératoire , insuffisance hépatique sévère (TP < 50% hors prise d'AVK) , sévère hypotension et tachycardie , antécédent de torsade de pointe , obstruction dynamique de la chambre de chasse du VG).

E.5 End points

E.5.1

Primary end point(s)

Le critère de jugement principal est un critère composite qui reflète la présence d'un SBDC avéré. Ce critère regroupe :
(1) l'utilisation d'agent inotrope positif au-delà de la 24ème heure après la fin de la perfusion du médicament à l'étude (soit 48 heures après l'induction anesthésique) ; ou
(2) le recours à des techniques d'assistance circulatoire mécanique (BCPIA, ECLS) ou l'absence d'arrêt de celles-ci si elles existent en préopératoire au-delà de la 96ème heure ; ou
(3) le recours à une technique d'épuration extra-rénale (hémodialyse conventionnelle intermittente ou hémofiltration continue) pendant le séjour en réanimation.

Les critères retenus pour évaluer la mortalité sont :
- la mortalité pendant le séjour hospitalier
- la mortalité à J 28
- la mortalité à J 180.

Les critères retenus pour étudier l'impact économique sont :
- le nombre total de jours hors-hôpital à J28.
- le nombre de jours d'hospitalisation en unité de réanimation et en service conventionnel
- le nombre total de jours hors-ventilateur pendant le séjour hospitalier
- la quantité totale d'inotropes positifs injectés et la durée de leurs perfusions
- le nombre de jours sous assistance circulatoire mécanique
- le nombre d'heures d'épuration extra-rénale et le nombre de circuits et de cathéters utilisés.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

Yes

E.6.4

Safety

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

Information not present in EudraCT

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

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.8.3

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

Information not present in EudraCT

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

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	No
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	Yes
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
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 2012-08-27.	Yes
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	340

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

2012-06-08

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-06-27

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

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