Clinical Trials Register

Summary
EudraCT Number:	2011-002555-34
Sponsor's Protocol Code Number:	ECSEVO-LT-011
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:	2011-10-28
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

2011-002555-34

A.3

Full title of the trial

Study on the safety of administration of sevoflurane for long-term sedation in critical patients on assisted ventilation. A multicentric, randomised, controlled, prospective clinical trial.

Estudio sobre la seguridad de administración de sevoflurano a largo plazo para la sedación de pacientes críticos con ventilación asistida. Estudio multicéntrico, aleatorizado, controlado, clínico prospectivo.

A.3.1

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

Study on the safety of administration of sevoflurane for long-term sedation in critical patients on assisted ventilation.

Estudio sobre la seguridad de la administración de sevoflurano a largo plazo para la sedación de pacientes críticos con ventilación asistida.

A.3.2

Name or abbreviated title of the trial where available

sevoflurane for long-term sedation

A.4.1

Sponsor's protocol code number

ECSEVO-LT-011

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	FRANCISCO JAVIER BELDA
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	Sedana Medical AB
B.4.2	Country	Sweden
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Francisco Javier Belda
B.5.2	Functional name of contact point	Critical Care Department. Hospital
B.5.3	Address:
B.5.3.1	Street Address	Blasco Ibañez, 17
B.5.3.2	Town/ city	Valencia
B.5.3.3	Post code	46010
B.5.3.4	Country	Spain
B.5.4	Telephone number	34963862651
B.5.5	Fax number	34963987831
B.5.6	E-mail	fjbelda@uv.es

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	Abbott Laboratories
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.3.2	Product code	12164-005
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	sevorane
D.3.9.1	CAS number	28523-86-6
D.3.9.2	Current sponsor code	sevorane
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	% percent
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	MIDAZOLAM
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Farma
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	MIDAZOLAM
D.3.2	Product code	0409-2306
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	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	MIDAZOLAM
D.3.9.1	CAS number	59467-70-8
D.3.9.2	Current sponsor code	Roche Farma
D.3.9.3	Other descriptive name	Midazolam
D.3.9.4	EV Substance Code	SUB08950MIG
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	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

The general objective of this study is to perform an assessment of the safety of administration of sevoflurane for prolonged sedation of patients admitted to the Critical Care Unit.

El objetivo general de este estudio es realizar una evaluación de la seguridad de la administración de sevofluorano para la sedación prolongada de los pacientes ingresados en la Unidad de Cuidados Intensivos.

E.1.1.1

Medical condition in easily understood language

The general objective of this study is to perform an assessment of the safety of administration of sevoflurane for prolonged sedation of patients admitted to the Critical Care Unit.

Evaluar la seguridad y la eficacia de la sedación prolongada con sevofluorano en pacientes críticos.

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	14.0
E.1.2	Level	SOC
E.1.2	Classification code	10042613
E.1.2	Term	Surgical and medical procedures
E.1.2	System Organ Class	10042613 - Surgical and medical procedures

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 determine whether sevoflurane, an inhalatory anesthetic used in anesthesia procedures with a maximum duration of 12 hours, can be administered as a sedative for over 48 hours without clinically relevant physiopathological effects upon kidney and liver function.

Para determinar si el sevofluorano, un anestésico inhalatorio utilizado en los procedimientos de anestesia con una duración máxima de 12 horas, puede ser administrado como un sedante para más de 48 horas sin efectos fisiopatológicos clínicamente relevantes sobre la función renal y hepática.

E.2.2

Secondary objectives of the trial

To compare the quality of sedation afforded by sevoflurane versus midazolam, in terms of sedation control, the rapidity and predictability of awakening, and the incidence of delirium in critical care patients.

Comparar la calidad de la sedación proporcionada por sevoflurano versus midazolam, en términos de control de sedación, la rapidez y la previsibilidad de despertar, y la incidencia de delirio en los pacientes de cuidados críticos.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Signing of the informed consent document (patient or relatives).
- Patient age 18 years or older.
- Expected minimum duration of sedation: 48 hours.

- Firma del documento de consentimiento informado (paciente o sus familiares).
- Paciente de 18 años o más.
- Duración mínima prevista de la sedación: 48 horas.

E.4

Principal exclusion criteria

- Known allergy to any of the study drugs.
- Patients with known or suspected genetic susceptibility to malignant hyperthermia.
- Renal failure (3 AKIN classification)
- Liver failure: C Chaild-Pugh.
- History of chronic alcohol abuse or neurological disease.
- Pregnant or breastfeeding women.

- Alergia conocida a cualquiera de los fármacos del estudio.
- Pacientes con susceptibilidad genética conocida o sospechada a hipertermia maligna.
- Insuficiencia renal (3 clasificación AKIN)
- Insuficiencia hepática: C Chaild-Pugh.
- Historia de abuso crónico de alcohol o enfermedades neurológicas.
- Las mujeres embarazadas o lactantes.

E.5 End points

E.5.1

Primary end point(s)

Determinations for evaluating renal function:
Measurements in plasma: creatinine, cystatin C, urea, uric acid and erythropoietin.
Measurements in urine: creatinine, creatinine clearance, glucose, proteins, albumin, sodium and osmolarity.

Determinaciones para evaluar la función renal:
Mediciones en plasma: creatinina, cistatina C, urea, ácido úrico y eritropoyetina.
Mediciones en orina: creatinina, aclaramiento de creatinina, glucosa, proteínas, sodio albúmina y osmolaridad.

E.5.1.1

Timepoint(s) of evaluation of this end point

Sampling timepoints:
- Baseline: immediately before starting to administer the sedating agent.
- Posteriorly, sampling will be made every 12 hours for the full length of sedation.
- After suspending sedation, sampling will be repeated during 7 days every 24 hours.

Puntos de tiempo de muestreo:
- Inicialmente: inmediatamente antes de comenzar a administrar el agente sedante.
- Posteriormente, el muestreo se realizará cada 12 horas hasta de la sedación.
- Después de la suspensión de la sedación, el muestreo se repitió durante siete días cada 24 horas.

E.5.2

Secondary end point(s)

1. SGOT (aspartate aminotransferase, AST), SGPT (alanine aminotransferase, ALT), LDH (lactate dehydrogenase) alkaline phosphatase, conjugated and total bilirubin, cholesterol, triglycerides, albumin, total proteins, electrolytes and glycogen.
3. Quality of sedation

1. GOT (aspartato aminotransferasa, AST), GPT (alanina aminotransferasa, ALT), LDH (lactato deshidrogenasa) fosfatasa alcalina, bilirrubina conjugada y total, colesterol, triglicéridos, albúmina, proteínas totales, los electrolitos y el glucógeno.
2. Calidad de la sedación

E.5.2.1

Timepoint(s) of evaluation of this end point

1 Plasma fluoride levels and Liver function markers:
- Baseline: immediately before starting to administer the sedating agent.
- Posteriorly, sampling will be made every 12 hours for the full length of sedation.
- After suspending sedation, sampling will be repeated during 7 days every 24 hours.

2. The assessment Quality of sedation
Before starting administration of the study sedative drug.
- Every hour since the time of start of administration of the drug continuing until the end of infusion.
- After discontinuing the study drug, every 4 hours the first 24 hours.

1 Niveles de flúor en plasma y los marcadores de la función hepática:
- Inicialmente: inmediatamente antes de comenzar a administrar el agente sedante.
- Posteriormente, el muestreo se realizará cada 12 horas hasta el final de la sedación.
- Después de la suspensión de la sedación, el muestreo se repetirá durante siete días cada 24 horas.

2. Evaluación de la calidad de la sedación
Antes de la administración a partir del estudio de drogas sedantes.
- Cada hora desde el momento de inicio de la administración de la droga hasta el final de la infusión.
- Después de la interrupción del fármaco a estudio, cada 4 horas las primeras 24 horas.

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)

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

Yes

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

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

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

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

Given the situation of the patient when the informed consent is obtained, a sedated patient on assisted ventilation, the legally authorised representative should sign the consent form

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)

Plans for treatment or care after the subject has ended the participation in the trial is not different from the expected normal treatment of that condition

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

2011-11-25

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-11-11

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

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