Clinical Trials Register

Summary
EudraCT Number:	2016-003413-10
Sponsor's Protocol Code Number:	ACDHUVV-16
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:	2016-09-09
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

2016-003413-10

A.3

Full title of the trial

MicroRNAs expression analysis in patients undergoing cardiac surgery treated with halogenated anesthetics. Identification of microRNAs related to the cardioprotective effect

Análisis de la expresión de microRNAs en pacientes sometidos a cirugía cardiaca tratados con anestésicos halogenados. Identificación de microRNAs relacionados con el efecto cardioprotector

A.3.1

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

Assessment of the possible protective effect of anesthetics on the heart in patients undergoing cardiac surgery.

Evaluación del posible efecto protector de los anestésicos halogenados sobre el corazón en los pacientes sometidos a cirugía cardiaca.

A.4.1

Sponsor's protocol code number

ACDHUVV-16

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	FIMABIS
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	Clinical Trials Unit
B.5.3	Address:
B.5.3.1	Street Address	Avda. Carlos Haya s/n
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@fimabis.org

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	SEVORANE
D.2.1.1.2	Name of the Marketing Authorisation holder	ABBVIE PHARMACEUTICAL SLU
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	SEVOFLURANE
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.3.9.3	Other descriptive name	SEVOFLURANE
D.3.9.4	EV Substance Code	SUB10506MIG
D.3.10	Strength
D.3.10.1	Concentration unit	ml millilitre(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1
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	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	DIPRIVAN
D.2.1.1.2	Name of the Marketing Authorisation holder	ASTRA ZENECA
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.3.4	Pharmaceutical form	Emulsion for injection/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	PROPOFOL
D.3.9.3	Other descriptive name	PROPOFOL
D.3.9.4	EV Substance Code	SUB10116MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/kg milligram(s)/kilogram
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	1.2 to 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	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: 3
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 LIPOMED FRESENIUS
D.2.1.1.2	Name of the Marketing Authorisation holder	FRESENIUS KABI
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.3.4	Pharmaceutical form	Emulsion for injection/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	PROPOFOL
D.3.9.3	Other descriptive name	PROPOFOL
D.3.9.4	EV Substance Code	SUB10116MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/kg milligram(s)/kilogram
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	1.2 to 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	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

Cardiac surgery

Cirugía cardiaca

E.1.1.1

Medical condition in easily understood language

Cardiac surgery

Cirugía cardiaca

E.1.1.2

Therapeutic area

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

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

1. Analyze variation of microRNAs in human serum of patients at high risk of ischemic heart disease undergoing coronary artery bypass surgery with pre and postoperative administration of sevoflurane (cardioprotective effect) compared with those who were he administered propofol (no cardioprotective effect described).
2. Analyze variation in cardioprotective microRNAs expression levels using a quantitative technique, in human serum of patients at high risk of ischemic heart disease undergoing cardiac pre-postconditionings protocol with sevoflurane anesthesia.
3. Analyze the initial and final levels of various serum microRNA in human patients at high risk of ischemic heart disease, and analyze whether there is a correlation between this variation and the morbidity and mortality of patients.

1. Analizar cúales son los microRNAs que varían en el suero humano en pacientes con alto riesgo de cardiopatía isquémica, intervenidos de cirugía de revascularización miocárdica, donde se administra sevoflurano pre y post operatoria (cardioprotectores), en comparación con aquellos a los que se les administró propofol.
2. Analizar la variación en los niveles de expresión de microRNAs cardioprotectores, a través de técnica cuantitativa, en suero humano de pacientes con alto riesgo de cardiopatía isquémica sometidos al protocolo de pre-post-condicionamiento cardiaco con anestesia con sevoflurano.
3. Analizar los niveles inicial y final de varios microRNA del suero en humanos de pacientes con alto riesgo de cardiopatía isquémica, y analizar si existe una correlación entre dicha variación y la morbimortalidad de los pacientes.

E.2.2

Secondary objectives of the trial

Not applicable

No aplica

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Age ≥ 18 year old.
2. Elective off-pump coronary artery bypass surgery.
3. EUROSCORE (European level of risk, useful in the perioperative period of patients undergoing cardiac surgery, validated at medical and scientific level) under 8 (cardiological moderate risk in the perioperative).
4. Degree of anesthetic risk according to the American Society of Anesthesiologists (ASA) less than 4 (moderate-risk patient high anesthetic).

1. Edad ≥ de 18 años.
2. Cirugía electiva de revascularización miocárdica sin bomba.
3. EUROSCORE (escala europea de riesgo, útil en el perioperatorio de los pacientes intervenidos de cirugía cardiaca, validada a nivel médico y científico) menor de 8 (riesgo moderado cardiológico en el perioperatorio).
4. Grado de riesgo anestésico según la sociedad americana de anestesia (ASA) menor de 4 (paciente de riesgo anestésico moderado-alto).

E.4

Principal exclusion criteria

1. History of adverse reaction to anesthetic drugs.
2. Severe illness of any organ (lung, liver, kidney), diagnosed preoperatively.
3. Combined surgery (eg valve repair or carotid surgery).
4. Patients in situations of hemodynamic instability.
5. Heart failure or need for use of inotropes or vasoactive pre-intervention.
6. Treatment with oral antidiabetic drugs at least 48 hours before.
7. Pre-intervention treatment with eufilina/theophylline.
8. Inability to grant informed consent.
9. Pregnancy or breastfeeding.

1. Historia de reacción adversa a los distintos fármacos anestésicos.
2. Enfermedad severa de cualquier órgano (pulmón, hígado, riñón), diagnostica de manera preoperatoria.
3. Cirugía combinada (ejemplo reparación valvular o de cirugía carotidea).
4. Pacientes en situación de inestabilidad hemodinámica.
5. Insuficiencia cardiaca 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)

1. Damage and myocardial injury (NT-proBNP levels, troponinaI, CK and CKMMB).
2. Cardiac Output Index

1.Daño y lesión miocárdica (niveles de NT-ProBNP, troponinaI, CK y CKMMB)
2.Índice cardiaco

E.5.1.1

Timepoint(s) of evaluation of this end point

Discharge Report of intensive care unit

Registro de alta de la unidad de cuidados intensivos

E.5.2

Secondary end point(s)

1. Arrhythmias.
2. Number of days in Intensive Care Unit
3. Total number of days hospitalised.
4. MicroRNA quantitative values.
5. Mortality rate.

1. ARRITMIAS
2. DIAS DE ESTANCIA EN UCI
3. DIAS DE ESTANCIA EN HOSPITAL
4. VALORES MICRORNA
5. MORTALIDAD

E.5.2.1

Timepoint(s) of evaluation of this end point

Hospital Discharge Report (postsurgery)

Registro de alta médica postoperacional.

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

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

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

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:

128

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

128

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

2016-12-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-12-16

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

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