Clinical Trials Register

Summary
EudraCT Number:	2012-005310-19
Sponsor's Protocol Code Number:	PI-0697-2012
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2013-02-04
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

Spain - AEMPS

A.2

EudraCT number

2012-005310-19

A.3

Full title of the trial

Double-blind randomized clinical trial to evaluate the efficacy and safety of levosimendan as preischemic myocardial conditioner in pediatric cardiac surgery

Ensayo clínico aleatorizado doble ciego para evaluar la eficacia y seguridad de levosimendán como acondicionador miocárdico preisquémico en pacientes pediátricos de cirugía cardíaca.

A.3.1

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

randomized clinical trial which included patients aged 1 month to 14 years who are to undergo cardiac surgery with high risk factors of postoperative acute heart failure to evaluate the efficacy and safety of levosimendan

A.4.1

Sponsor's protocol code number

PI-0697-2012

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	FUNDACION PARA LA INVESTIGACIÓN BIOSANITARIA DE ANDALUCIA ORIENTAL_ FPA
B.1.3.4	Country	Spain
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	Hospital Virgen de las Nieves
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Hospital Virgen de Las Nieves
B.5.2	Functional name of contact point	HVN
B.5.3	Address:
B.5.3.1	Street Address	Fuerzas Armadas s/n
B.5.3.2	Town/ city	Granada
B.5.3.3	Post code	18014
B.5.3.4	Country	Spain
B.5.4	Telephone number	0034958020097
B.5.6	E-mail	anabril15@hotmail.com

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.2.1.1.2	Name of the Marketing Authorisation holder	ORION PHARMA
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	levosimendan
D.3.2	Product code	C01CX.
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.3.11 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	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

Children aged 1 month to 14 years in the health area of the province of Granada who will be undergoing heart surgery with a clinical high risk of developing acute heart failure after surgery, treated at the Unit Pediatric Intensive Care, University Hospital Virgen de las Nieves.

E.1.1.1

Medical condition in easily understood language

Children with congenital heart disease that will be operate.

E.1.1.2

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutic techniques [E02]

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

To evaluate the efficacy and safety of levosimendan on myocardial preischemic conditioning in pediatric cardiac surgery child

E.2.2

Secondary objectives of the trial

1. To evaluate the effect of levosimendan on cardiac function.
2. Estimating the changes in the neurohormonal profile and promotes enzymatic levosimendan.
3. Evaluate serious adverse events that may appear in both groups.
4. Evaluate all-cause mortality.
5. Conduct an analysis of economic impact of using levosimendan.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

(existing mandatory general criteria: the existence of an informed consent of father / mother / guardian): patients at high risk of developing postoperative acute heart failure, for which require at least two of the following factors: age less than 6 months or less to 7kg weight at the time of surgery, patients in heart failure situation before surgery, bypass time estimated by the complexity of the surgery than 100 minutes, preoperative patients with pulmonary hypertension or increased risk of hypertension postoperative lung.

E.4

Principal exclusion criteria

Negative states of parents or guardians to participate in the study or refusal to sign the informed consent of the father / mother / guardian.
-Not meet at least two of the factors include or found before surgery in low cardiac output state set.
- Allergy or hypersensitivity to other components Levosimendan Simdax ®.
-Patients who can not prescribe medication be contraindicated as study sheet: mechanical obstructions affecting ventricular filling or discharge or both, severe renal impairment (CrCl <30 ml / min), severe hepatic impairment, hypotension refractory malignant arrhythmias (Torsades de Pointes).
-History of autoimmune disease.

E.5 End points

E.5.1

Primary end point(s)

Hemodynamic:
12. Heart rate (HR) (bpm).
13. Mean arterial pressure (MAP) (mmHg)
14. Central venous pressure (CVP) (cmH20) (measured by placement of a central venous catheter in the right atrium)
15. Thermal gradient (measured in centigrade)
16. Capillary refill time (seconds)
17. Diuresis (ml / kg / hr)
18. Total dose of inotropic score VIS expressed as: (dose dopamine and dobutamine) + (milrinone × 10) + (adrenaline and noradrenaline x 1000) + (vasopresinax10)
19. Adrenaline, noradrenaline, dopamine, dobutamine and milrinone (mcg / kg / min)
b) Analytical:
20. Cardiac Profile: atrial natriuretic peptide (BNP) (pg / dL), Troponin-I (TP-I) (ng / ml) and myoglobin (Mb) (ng / ml).
21. Metabolic profile: lactate: mmol / l, central venous oxygen saturation (Sav02) (%), oxygen transport (ml/min/m2).

E.5.1.1

Timepoint(s) of evaluation of this end point

at 0 hours, 12 and 24 hour after arraiving from surgery room

E.5.2

Secondary end point(s)

days in PICU, days of mechanical ventilation, development
C complications or serious adverse events (arrhythmias, hypotension requiring suspension, kidney or liver failure, death), survival at 30 days.

E.5.2.1

Timepoint(s) of evaluation of this end point

at 30 day after surgery

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

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)

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

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.8.5

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

Usual inotropic therapy of acute heart failure in children after cardiac surgery carries an increased oxygen consumption and increased risk of arrhythmias and cell death. Levosimendan belongs to a new class of calcium sensitizers, that achieves greater inotropic potency equal to intracellular calcium concentration compared to normal inotropes. This ensures that there is no increase in myocardial oxygen consumption, the main drawback of other inotropes.

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

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)

Yes

F.1.1.4.1

Number of subjects for this age range:

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

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

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

children with congenital heart disease

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

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

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

2013-06-05

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-12-07

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

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