Clinical Trials Register

Summary
EudraCT Number:	2022-003638-38
Sponsor's Protocol Code Number:	FIM-SEV-2022-01
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:	2023-04-11
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

2022-003638-38

A.3

Full title of the trial

CARDIOPROTECTIVE-NEPHROPROTECTIVE EFFECTS OF SEVOFLURAN IN COMPARISON WITH PROPOFOL IN DOUBLE VALVULAR SURGERY. USE OF SEVOFLURANE AS A PILLAR OF PROTECTION IN EXTRACORPOREA CIRCULATION AND POSTOPERATIVE SEDATION

EFECTOS CARDIOPROTECTORES-NEFROPROTECTOR DEL SEVOFLURANO EN COMPARACION CON EL PROPOFOL EN CIRUGIA DOBLE VALVULAR. USO DEL SEVOFLURANO COMO PILAR DE LA PROTECCION EN LA CIRCULACION EXTRACORPOREA Y SEDACION POSTOPERATORIA

A.3.1

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

CARDIOPROTECTIVE-NEPHROPROTECTIVE EFFECTS OF SEVOFLURAN IN COMPARISON WITH PROPOFOL IN DOUBLE VALVULAR SURGERY.

EFECTOS CARDIOPROTECTORES-NEFROPROTECTOR DEL SEVOFLURANO EN COMPARACION CON EL PROPOFOL EN CIRUGIA DOBLE VALVULAR

A.3.2

Name or abbreviated title of the trial where available

FPS-0168-2021

A.4.1

Sponsor's protocol code number

FIM-SEV-2022-01

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	FIMABIS
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	Fundacion Progreso y Salud
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	FIMABIS
B.5.2	Functional name of contact point	Gloria Luque
B.5.3	Address:
B.5.3.1	Street Address	Avda Carlos Haya s/n. Hospital Regional Universitario. 7ª, PA
B.5.3.2	Town/ city	Malaga
B.5.3.3	Post code	29010
B.5.3.4	Country	Spain
B.5.4	Telephone number	34951291977
B.5.5	Fax number	34951440263
B.5.6	E-mail	gloria.luque@ibima.eu

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	PROPOFOL
D.2.1.1.2	Name of the Marketing Authorisation holder	Diprivan®; AstraZeneca, Brussels, Belgium
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	Propofol
D.3.2	Product code	N01AX10
D.3.4	Pharmaceutical form	Emulsion for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Concentrate for solution for infusion (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Propofol
D.3.9.1	CAS number	2078-54-8
D.3.9.2	Current sponsor code	SUB10116MIG
D.3.9.4	EV Substance Code	SUB10116MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	20 to 40/10 sec
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.IMP: 2
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	SEVOFLURANO
D.2.1.1.2	Name of the Marketing Authorisation holder	BAXTER
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	SEVOFLURANO
D.3.4	Pharmaceutical form	Inhalation vapour, liquid
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Inhalation use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Sevoflurane
D.3.9.1	CAS number	28523-86-6
D.3.9.2	Current sponsor code	SUB10506MIG
D.3.9.4	EV Substance Code	SUB10506MIG
D.3.10	Strength
D.3.10.1	Concentration unit	% (V/V) percent volume/volume
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
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

DOBLE VALVE SURGERY

CIRUGÍA DOBLE VALVULAR

E.1.1.1

Medical condition in easily understood language

DOBLE VALVE TREATMENT

TRATAMIENTO ENFERMEDAD DOBLE VALVULAR

E.1.1.2

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	HLT
E.1.2	Classification code	10007615
E.1.2	Term	Cardiac valve therapeutic procedures
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

Evaluar los efectos de la administración de sevoflurano en el intra (incluido el periodo de isquemia de la circulación extracorpórea) y postoperatorio de los pacientes intervenidos de cirugía doble valvular respecto al propofol en cuanto a disminución del daño y lesión miocárdica. Para ello se medirán los niveles de NT- ProBNP, y troponina I; y su repercusión en la preservación miocárdica, a través de la medición del índice cardiaco en el intraoperatorio y postoperatorio inmediato, así como el uso de inotrópicos por síndrome de bajo gasto cardiaco.

Evaluar la función renal en pacientes intervenidos de cirugía de doble recambio valvular, donde se mantiene el sevoflurano como agente hipnótico intra y postoperatorio en comparación con el grupo de pacientes donde se administró propofol. Para ello se medirán los valores de N-GAL, creatinina, y producción de orina (estos 2 últimos necesarios para la clasificación del estadiaje renal con la clasificación AKIN)

E.2.2

Secondary objectives of the trial

To assess whether there is a relationship between the new circRNA biomarkers, in their basal expression, and their variation at 24 hours, with the clinical conditions evaluated (cardiac or renal dysfunction).

Evaluate whether there is a relationship between the new circRNA biomarkers, in their basal expression, and their variation at 24 hours between the different treatment groups (assessing their variation with those of fundamental enzymes in the myocardial conditioning pathways).

Evaluar si existe relación de los nuevos biomarcadores circRNA, en su expresión basal, y su variación a las 24 horas con los cuadros clínicos evaluados (disfunción cardiaca o renal).

Evaluar si existe relación de los nuevos biomarcadores circRNA, en su expresión basal, y su variación a las 24 horas entre los distintos grupos de tratamiento (evaluando su variación con las de las de enzimas fundamentales en las rutas acondicionamiento miocárdico).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Age ≥ 18 years.
2. Elective surgery heart surgery with double valve pump.
3. Use of Nido cardioplegia, common in this type of patient.

1. Edad ≥ de 18 años.
2. Cirugía electiva cirugía cardíaca con bomba doble valvular.
3. Uso de cardioplejía del Nido, habitual en este tipo de pacientes.

E.4

Principal exclusion criteria

1. History of adverse reaction to sevoflurane or propofol.
2. Severe disease of any organ (lung, liver, kidney), diagnosed preoperatively.
3. Combined surgery (eg coronary or carotid surgery).
4. Patients in a situation of hemodynamic instability (defined as heart rate variation or TAM>20% from baseline)
5. Heart failure or the need to use inotropic or vasoactive drugs prior to the intervention.
6. Treatment with oral antidiabetics not suspended at least 48 hours before.
7. Treatment with euphylline/theophylline prior to the intervention.
8. Inability to give informed consent.
9. Pregnancy or lactation.

1. Historia de reacción adversa al sevoflurano o propofol.
2. Enfermedad severa de cualquier órgano (pulmón, hígado, riñón), diagnostica de manera preoperatoria.
3. Cirugía combinada (ejemplo coronaria o de cirugía carotidea).
4. Pacientes en situación de inestabilidad hemodinámica (definido como variación de la frecuencia cardíaca o TAM>20% respecto a la basal)
5. Insuficiencia cardíaca o necesidad de uso de fármacos inotrópicos o vasoactivos previos a la intervención.
6. Tratamiento con antidiabéticos orales no suspendido al menos 48 horas antes.
7. Tratamiento con eufilina/teofilina previo a la intervención.
8. Incapacidad para otorgar el consentimiento informado.
9. Embarazo o lactancia.

E.5 End points

E.5.1

Primary end point(s)

To evaluate the effects of sevoflurane administration intraoperatively (including the period of extracorporeal circulation ischemia) and postoperatively of patients undergoing double valve surgery with respect to propofol in terms of reduction of myocardial damage and injury. For this, the levels of NT-ProBNP and troponin I will be measured; and its impact on myocardial preservation, through the measurement of the cardiac index in the intraoperative and immediate postoperative period, as well as the use of inotropes for low cardiac output syndrome.

To evaluate renal function in patients undergoing double valve replacement surgery, where sevoflurane is maintained as an intra- and postoperative hypnotic agent compared to the group of patients where propofol was administered. For this, the values of N-GAL, creatinine, and urine production will be measured (these last 2 necessary for the classification of renal staging with the AKIN classification)

E.5.1.1

Timepoint(s) of evaluation of this end point

3 days

3 días

E.5.2

Secondary end point(s)

E.5.2.1

Timepoint(s) of evaluation of this end point

3 days

3 días

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

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

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)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

SEVOFLURANO

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

LVLP

última visita del último paciente

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:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

Subjects incapable of giving consent personally may participate

Podían participar sujetos incapaces para dar su consentimiento

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)

The patient will receive the best treatment available in the follow-up

El paciente recibirá el mejor tratamiento disponible en su seguimiento

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

2023-04-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2023-02-23

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

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