Clinical Trials Register

Summary
EudraCT Number:	2018-002701-59
Sponsor's Protocol Code Number:	IIBSP-CAR-2018-71
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:	2019-05-17
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

2018-002701-59

A.3

Full title of the trial

Randomized, open and multi-center clinical trial to compare the efficacy and safety of Buckberg vs Del Nido cardioplegia in isolated aortic valve replacement

Ensayo clínico aleatorizado, abierto y multicéntrico para comparar la eficacia y seguridad de la cardioplegia Buckberg vs Del Nido en sustitución valvular aórtica aislada

A.3.1

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

Study to compare Buckberg cardioplegia and Del Nido cardioplegia in isolated aortic valve replacement surgery

Estudio para comparar la cardioplegia de Buckberg y la cardioplegia Del Nido en cirugía de sustitución valvular aórtica aislada

A.4.1

Sponsor's protocol code number

IIBSP-CAR-2018-71

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	Institut de Recerca Hospital de la Santa Creu i Sant Pau
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	Institut de Recerca Hospital de la Santa Creu i Sant Pau
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	Institut de Recerca Hospital de la Santa Creu i Sant Pau
B.5.2	Functional name of contact point	UICEC Sant Pau
B.5.3	Address:
B.5.3.1	Street Address	Sant Quintí 77-79
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08041
B.5.3.4	Country	Spain
B.5.4	Telephone number	+34935537636
B.5.5	Fax number	+34935537812
B.5.6	E-mail	epenag@santpau.cat

D. IMP Identification
D.IMP: 1
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	Cardi-Braun
D.2.1.1.2	Name of the Marketing Authorisation holder	B. Braun Medical, SA
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.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intracoronary use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	TROMETAMOL CITRATE
D.3.9.3	Other descriptive name	TROMETAMOL CITRATE
D.3.9.4	EV Substance Code	SUB04993MIG
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	8.7560
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	SODIUM CITRATE
D.3.9.3	Other descriptive name	SODIUM CITRATE
D.3.9.4	EV Substance Code	SUB12582MIG
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	1.5840
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CITRIC ACID MONOHYDRATE
D.3.9.3	Other descriptive name	CITRIC ACID MONOHYDRATE
D.3.9.4	EV Substance Code	SUB76183
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	0.1976
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	POTASSIUM CHLORIDE
D.3.9.3	Other descriptive name	POTASSIUM CHLORIDE
D.3.9.4	EV Substance Code	SUB12559MIG
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	1.7960
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	SODIUM CHLORIDE
D.3.9.3	Other descriptive name	SODIUM CHLORIDE
D.3.9.4	EV Substance Code	SUB12581MIG
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	9.8600
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	GLUCOSE MONOHYDRATE
D.3.9.3	Other descriptive name	GLUCOSE MONOHYDRATE
D.3.9.4	EV Substance Code	SUB13983MIG
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	34.66
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

Myocardial protection

Protección miocárdica

E.1.1.1

Medical condition in easily understood language

Heart protection

Protección del corazón

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

To evaluate the efficacy and safety of myocardial protection with a cardioplegic solution of the Nido, compared to the Buckberg cardioplegic solution in patients undergoing isolated aortic valve replacement. This efficacy on myocardial protection will be measured by comparing the levels of markers of myocardial injury (CK and Troponin T) between both strategies, as well as in-hospital mortality.

Evaluar la eficacia y seguridad de la protección miocárdica con solución cardioplégica Del Nido, frente a la solución cardioplégica Buckberg en pacientes intervenidos de sustitución valvular aórtica aislada. Dicha eficacia sobre la protección miocárdica se medirá comparando los niveles de marcadores de lesión miocárdica (CK y Troponina T) entre ambas estrategias, así como mortalidad hospitalaria.

E.2.2

Secondary objectives of the trial

To compare other markers of myocardial injury such as LVEF by transthoracic echocardiography, postoperative inotropic need, spontaneous recovery of the post-disinfestation cardiac rhythm or the need for defibrillation.

To compare other markers of hemodilution (minimum intraoperative and postoperative hemoglobin and need for transfusion), intra and postoperative glucose and insulin needs, other intraoperative analytical parameters such as intraoperative maximum lactate, aortic clamping times and CPB between both types of cardioplegia.

Comparar otros marcadores de lesión miocárdica como FEVI por ecocardiografia transtorácica, necesidad de inotrópicos postoperatorios, recuperación espontanea del ritmo cardiaco post-despinzamiento o necesidad de desfibrilación.

Comparar otros parámetros marcadores de hemodilución (hemoglobina mínima intraoperatoria y postoperatoria y necesidad de transfusión), glucosa intra y postoperatoria y necesidades de insulina, otros parámetros analíticos intraoperatorios como lactato máximo intraoperatorio, tiempos de pinzamiento aórtico y CEC entre ambos tipos de cardioplegia.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patients of legal age (> 18 years) of both sexes

Patients who were electively operated on isolated aortic valve replacement in any of the three participating centers.

Patients who give informed consent

Pacientes mayores de edad (>18 años) de ambos sexos

Pacientes intervenidos electivamente de sustitución valvular aórtica aislada en cualquiera de los tres centros participantes.

Pacientes que otorguen el consentimiento informado

E.4

Principal exclusion criteria

Urgent or emergent surgery

Patients who refuse transfusion of blood products

Patients who do not accept to participate

Cirugía urgente o emergente

Pacientes que rechacen transfusión de hemoderivados

Pacientes que no acepten participar

E.5 End points

E.5.1

Primary end point(s)

Peak levels of CK in U / L and ultrasensitive Troponin T in ng / L in blood during the postoperative period: the levels of CK and Troponin T in blood will be determined in the first 24 hours postoperatively and later on a daily basis until the peak of both parameters is determined (usually occurs between 2 and 4 days postoperatively). The peak of CK and Troponin T of each of the study subjects will be recorded.

Operative mortality: Operative mortality will be considered, mortality within 30 days after surgery, or mortality during admission of the intervention (in patients whose hospital stay exceeds 30 days postoperatively).

Niveles pico de CK en U/L y Troponina T ultrasensible en ng/L en sangre durante el postoperatorio: se determinarán los niveles de CK y Troponina T en sangre las primeras 24 horas postoperatorias y posteriormente de manera diaria hasta determinar el pico de ambos parámetros (usualmente se produce entre 2 y 4 días postoperatorios). Se registrará el pico de CK y de Troponina T de cada uno de los sujetos de estudio.

Mortalidad operatoria. Se considerará mortalidad operatoria, la mortalidad en los siguientes 30 días a la intervención quirúrgica, o la mortalidad durante el ingreso de la intervención (en pacientes en que el ingreso supere los 30 días postoperatorios).

E.5.1.1

Timepoint(s) of evaluation of this end point

1 - 4 days and 30 days for each primary endpoint respectively

1 - 4 días y 30 días para cada variable primaria respectivamente

E.5.2

Secondary end point(s)

Spontaneous recovery of aortic post-release rhythm: it will be recorded during the intraoperative period if there is spontaneous recovery of the heart rhythm when removing the aortic clamp.
Need for post-aortic defibrillation: it will be recorded if defibrillation is necessary or not when removing the aortic clamp.
Need for inotropes for CEC disconnection: the administration of inotropes for the CEC disconnection will be recorded if necessary or not. If yes, it will also be recorded what inotropes are necessary and in what dose.
Minimum intraoperative hemoglobin (in g / L)
Need for transfusion of red blood cells
Maximum intraoperative glycemia (in mmol / L)
Intraoperative insulin needs
Insulin needs in the first 48 hours after surgery
Maximum intraoperative lactate (in mmol / L)
Aortic Impingement Time (minutes)
Extracorporeal circulation time (minutes)
Left ventricular function by echocardiography at discharge
Left ventricular function by echocardiography at 3-6 months postoperatively

Recuperación espontánea del ritmo post-despinzamiento aórtico: se registrará durante el periodo intraoperatorio si existe recuperación espontánea del ritmo cardiaco al retirar la pinza aórtica.
Necesidad de desfibrilación post-despinzamiento aórtico: se registrará si es necesaria desfibrilación o no al retirar la pinza aórtica.
Necesidad de inotrópicos para desconexión de CEC: se registrará si es necesario o no la administración de inotrópicos para la desconexión de CEC. En caso afirmativo, se registrará también qué inotrópicos son necesarios y en qué dosis.
Hemoglobina mínima intraoperatoria (en g/L)
Necesidad de transfusión de hematíes
Glucemia máxima intraoperatoria (en mmol/L)
Necesidades de insulina intraoperatoria
Necesidades de insulina en las primeras 48 horas postoperatorias
Lactato máximo intraoperatorio (en mmol/L)
Tiempo de pinzamiento aórtico (minutos)
Tiempo de circulación extracorpórea (minutos)
Función ventricular izquierda por ecocardiografia al alta
Función ventricular izquierda por ecocardiografia a los 3-6 meses postoperatorios

E.5.2.1

Timepoint(s) of evaluation of this end point

24 hours, 3 months and 6 months

24 horas, 3 meses y 6 meses

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)

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

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)

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

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

LVLS

Última visita del último sujeto

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.1.1.1

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:

398

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

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

388

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

Ninguno

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

2019-04-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-03-27

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

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