Clinical Trials Register

Summary
EudraCT Number:	2019-003855-12
Sponsor's Protocol Code Number:	REDOLEV-2019
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:	2019-12-02
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

2019-003855-12

A.3

Full title of the trial

Phase III Clinical Trial, single-center, randomized, double-blind, to demonstrate a lower incidence of acute diaphragmatic paralysis of the brachial plexus block with interscalene approach in arthroscopic shoulder surgery after administration of 25 mg of 0.25% Levobupivacaine compared to 50 mg administration

Ensayo Clínico Fase III, unicéntrico, aleatorizado, doble ciego, para demostrar una menor incidencia de parálisis diafragmática aguda del bloqueo del plexo braquial con abordaje interescalénico en la cirugía artroscópica de hombro tras la administración de 25 mg de Levobupivacaina 0,25% en comparación con la administración de 50 mg

A.3.1

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

Phase III Clinical Trial, single-center, randomized, double-blind, to demonstrate a lower incidence of acute diaphragmatic paralysis in shoulder surgery following the administration of 25 mg of 0.25% Levobupivacaine to block the brachial lead compared to the administration of 50 mg

Ensayo Clínico Fase III, unicéntrico, aleatorizado, doble ciego, para demostrar una menor incidencia de parálisis diafragmática aguda en la cirugía de hombro tras la administración de 25 mg de Levobupivacaina 0,25% para bloquear el plxo braquial en comparación con la administración de 50 mg.

A.4.1

Sponsor's protocol code number

REDOLEV-2019

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	Fundación Instituto de Investigación Sanitaria Aragón
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	Fundación Instituto de Investigación Sanitaria Aragón
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	Fundación Instituto de Investigación Sanitaria Aragón
B.5.2	Functional name of contact point	Unidad de Investigación Clínica
B.5.3	Address:
B.5.3.1	Street Address	Avda/ San Juan Bosco 13, Edificio CIBA, IIS Aragon, Planta Baja
B.5.3.2	Town/ city	Zaragoza
B.5.3.3	Post code	50009
B.5.3.4	Country	Spain
B.5.4	Telephone number	0034976713259
B.5.6	E-mail	pmillan@iisaragon.es

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	CHIROCANE 2,5 mg/ml SOLUCION INYECTABLE Y PARA PERFUSION
D.2.1.1.2	Name of the Marketing Authorisation holder	AbbVie Spain, S.L.U.
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 injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Perineural use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	LEVOBUPIVACAINE HYDROCHLORIDE
D.3.9.1	CAS number	27262-48-2
D.3.9.3	Other descriptive name	LEVOBUPIVACAINE HYDROCHLORIDE
D.3.9.4	EV Substance Code	SUB02904MIG
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	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: 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	Chirocane® 2,5 mg/ml Solución Inyectable y para perfusión
D.2.1.1.2	Name of the Marketing Authorisation holder	AbbVie Spain, S.L.U.
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 injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Perineural use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	LEVOBUPIVACAINE HYDROCHLORIDE
D.3.9.1	CAS number	27262-48-2
D.3.9.3	Other descriptive name	LEVOBUPIVACAINE HYDROCHLORIDE
D.3.9.4	EV Substance Code	SUB02904MIG
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	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

Patients who will undergo surgery for arthroscopic shoulder surgery

Pacientes que van a ser intervenidos quirúrgicamente de cirugía artroscópica de hombro

E.1.1.1

Medical condition in easily understood language

Patients who will be surgically operated on the shoulder

Pacientes que van a ser operados quirúrgicamente de hombro

E.1.1.2

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

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

Demonstrate a lower statistically significant incidence of acute diaphragmatic paralysis diagnosed by ultrasound using the Diaphragmatic Thickness Ratio after Brachial Plexus Block with ultrasound-guided interscholastic approach in scheduled arthroscopic shoulder surgery after administration of a 10 ml volume of Levobupivacaine 0 , 25% (25 mg dose) compared to 20 ml of 0.25% Levobupivacaine (50 mg dose).

Demostrar una menor incidencia estadísticamente significativa de parálisis diafragmática aguda diagnosticada por ecografía mediante el Ratio de Grosor Diafragmático tras el Bloqueo del Plexo Braquial con abordaje Interescalénico guiado por ecografía en la cirugía programada artroscópica de hombro tras la administración de un volumen de 10 ml de Levobupivacaina 0,25% (dosis 25 mg) en comparación con 20 ml de Levobupivacaina 0,25% (dosis 50 mg).

E.2.2

Secondary objectives of the trial

1 Demonstrate a lower incidence of acute diaphragmatic paralysis diagnosed by spirometry (FVC, FEV1 and PEF) after Brachial Plexus Blocking with ultrasound-guided interscholastic approach in scheduled arthroscopic shoulder surgery after 10 ml of Levobupivacaine (25 mg dose) compared with 20 ml (dose 50 mg).
2 Demonstrate a lower incidence of acute diaphragmatic paralysis diagnosed by ultrasound (Diaphragmatic excursion according to the number of intercostal spaces) after Brachial Plexus Blocking with ultrasound-guided interscholastic approach in scheduled arthroscopic shoulder surgery after administration of 10 ml of Levobupivacaine in comparison with 20 ml.
3 Demonstrate the non-inferiority of postoperative analgesia after Brachial Plexus Block with ultrasound-guided interscalenic approach in scheduled arthroscopic shoulder surgery after administration of a volume of 10 ml of Levobupivacaine compared to 20 ml.

1 Demostrar una menor incidencia de parálisis diafragmática aguda diagnosticada por espirometría (CVF, VEF1 y PEF) tras el Bloqueo del Plexo Braquial con abordaje Interescalénico guiado por ecografía en la cirugía programada artroscópica de hombro tras 10 ml de Levobupivacaina (dosis 25 mg) en comparación con 20 ml (dosis 50 mg).
2 Demostrar una menor incidencia de parálisis diafragmática aguda diagnosticada por ecografía (Excursión diafragmática según el número de espacios intercostales) tras el Bloqueo del Plexo Braquial con abordaje Interescalénico guiado por ecografía en la cirugía programada artroscópica de hombro tras la administración de10 ml de Levobupivacaina en comparación con 20 ml.
3 Demostrar la no inferioridad de analgesia postoperatoria tras el Bloqueo del Plexo Braquial con abordaje Interescalénico guiado por ecografía en la cirugía programada artroscópica de hombro tras la administración de un volumen de 10 ml de Levobupivacaina en comparación con 20 ml.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Written informed consent to participate in the clinical trial.
2. Be intervened with scheduled arthroscopic shoulder surgery.
3. Age between 18 and 80 years old,
4. ASA I-III.

1. Consentimiento informado por escrito para participar en el ensayo clínico.
2. Ser intervenido de cirugía programada artroscópica de hombro.
3. Edad comprendida entre 18 y 80 años,
4. ASA I-III.

E.4

Principal exclusion criteria

1. Allergic to local amide type anesthetics, opioids or nonsteroidal anti-inflammatory drugs.
2. Non-acceptance for the realization of the BBPAI.
3. Contraindication for the realization of the BPBAI,
4. Contraindication for performing a spirometry.
5. History of pulmonary pathology: moderate or severe COPD, or unstable asthma.
6. Previous diaphragmatic paralysis or other neuromuscular pathology with respiratory involvement,
7. Pregnancy
8. Coagulation disorders (INR> 3, TTPA> 35 and AP <50%).
9. Brachial plexus neuropathy.
10. Chronic opioid consumption: defined as the administration of opioids for more than 3 months or equivalent to more than 5 mg daily of VO Morphine for 1 month.

1. Alérgico a los anestésicos locales de tipo amida, a los opioides o a los antiinflamatorios no esteroideos.
2. No aceptación para la realización del BBPAI.
3. Contraindicación para la realización del BPBAI,
4. Contraindicación para la realización de una espirometría.
5. Antecedentes de patología pulmonar: EPOC moderada o severa, o asma inestable.
6. Parálisis diafragmática previa u otra patología neuromuscular con afectación respiratoria,
7. Embarazo.
8. Alteraciones de la coagulación (INR>3, TTPA > 35 y AP <50%).
9. Neuropatía del plexo braquial.
10. Consumo crónico de opioides: definido como la administración de opioides durante más de 3 meses o equivalente a más de 5 mg al dia de Morfina VO durante 1 mes.

E.5 End points

E.5.1

Primary end point(s)

This study aims to demonstrate that by decreasing the volume (20 ml to 10 ml) and the dose (50 mg to 25 mg) of local anesthetic used in a BPBAI in the usual clinical practice of arthroscopic shoulder surgery, a decreased PDA objectified by ultrasound and spirometry with maintenance of postoperative analgesia

Este estudio tiene como finalidad demostrar que al disminuir el volumen (20 ml a 10 ml) y la dosis (50 mg a 25 mg) de anestésico local utilizado en un BPBAI en la práctica clínica habitual de la cirugía artroscópica de hombro, se consigue una disminución de la PDA objetivada mediante ecografía y espirometría con un mantenimiento de la analgesia postoperatoria

E.5.1.1

Timepoint(s) of evaluation of this end point

1 hour post surgical intervention is measured:
1. Inspiratory diaphragmatic thickness.
2. Expiratory diaphragmatic thickness.
3. Inspiratory / expiratory diaphragmatic thickness ratio.

1 hora post operatorio se mide:
1. Grosor diafragmático inspiratorio.
2. Grosor diafragmático espiratorio.
3. Ratio del grosor diafragmático inspiratorio/espiratorio.

E.5.2

Secondary end point(s)

Incidence of acute diaphragmatic paralysis diagnosed by spirometry (FVC, FEV1 and PEF)
Incidence of acute diaphragmatic paralysis diagnosed by ultrasound (Diaphragmatic excursion according to the number of intercostal spaces).
No inferiority of postoperative analgesia after the Brachial Plexus Block with an ultrasound-guided Interscalene approach.

Incidencia de parálisis diafragmática aguda diagnosticada por espirometría (CVF, VEF1 y PEF)
Incidencia de parálisis diafragmática aguda diagnosticada por ecografía (Excursión diafragmática según el número de espacios intercostales).
No inferioridad de analgesia postoperatoria tras el Bloqueo del Plexo Braquial con abordaje Interescalénico guiado por ecografía.

E.5.2.1

Timepoint(s) of evaluation of this end point

1 hour post surgical intervention

1 hora post operatorio

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

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

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

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Diferentes dosis del mismo Producto en Investigación

different doses of the same IMP

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 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

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

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

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

2020-01-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-12-20

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

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