Clinical Trials Register

Summary
EudraCT Number:	2011-001490-40
Sponsor's Protocol Code Number:	3005019
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-03-12
Trial results	View 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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2011-001490-40

A.3

Full title of the trial

Comparative evaluation of the effects of dexmedetomidine and propofol on patient/ventilator interaction in difficult-to-wean mechanically ventilated patients; a prospective, open, randomised, multicentre study.

“Valutazione comparativa degli effetti della dexmedetomidina e del propofol sull’interazione paziente/ventilatore in pazienti in ventilazione meccanica che presentano difficolta' a discontinuare il supporto ventilatorio; studio prospettico, in aperto, randomizzato e multicentrico”

A.3.1

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

Confronto degli effetti di due sedativi, la dexmedetomidina e il propofol, in pazienti che hanno bisogno di ricominciare a respirare senza un macchinario e che hanno difficolta' a farlo.

A comparison of the effects of two calming drugs, dexmedetomidine and propofol, in patients who need to start breathing without the help of a machine and are having difficulty doing so.

A.3.2

Name or abbreviated title of the trial where available

DoVeS

A.4.1

Sponsor's protocol code number

3005019

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	ORION CORPORATION ORION PHARMA
B.1.3.4	Country	Finland
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Orion Corporation
B.4.2	Country	Finland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Orion Corporation
B.5.2	Functional name of contact point	Clinical Trials Information Desk
B.5.3	Address:
B.5.3.1	Street Address	Orionintie 1
B.5.3.2	Town/ city	Espoo
B.5.3.3	Post code	FI-02200
B.5.3.4	Country	Finland
B.5.4	Telephone number	+358 10 4261
B.5.5	Fax number	+358 10 426 7632
B.5.6	E-mail	clinicaltrials@orionpharma.com

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	No
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	Dexmedetomidine
D.3.2	Product code	NA
D.3.4	Pharmaceutical form	Concentrate for 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	DEXMEDETOMIDINE
D.3.9.1	CAS number	113775-47-6
D.3.9.4	EV Substance Code	NA
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
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.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	Propofol-Lipuro 20 mg/ml
D.2.1.1.2	Name of the Marketing Authorisation holder	B. Braun Melsungen AG
D.2.1.2	Country which granted the Marketing Authorisation	Finland
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	Emulsion 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	PROPOFOL
D.3.9.1	CAS number	2078-54-8
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	equal
D.3.10.3	Concentration number	20
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 requiring mechanical ventilation and sedation in the ICU

pazienti che richiedono ventilazione meccanica e sedazione in terapia intensiva.

E.1.1.1

Medical condition in easily understood language

patients who need to start breathing without the help of a machine and are having difficulty doing so.

Pazienti in ventilazione meccanica che presentano difficoltà a discontinuare il supporto ventilatorio.

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	14.1
E.1.2	Level	PT
E.1.2	Classification code	10039897
E.1.2	Term	Sedation
E.1.2	System Organ Class	10029205 - Nervous system disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	SOC
E.1.2	Classification code	10029205
E.1.2	Term	Nervous system disorders
E.1.2	System Organ Class	10029205 - Nervous system disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective is to investigate effects of dexmedetomidine on diaphragmatic neural activity (EAdi) over 24 hours after starting study treatment in difficult to wean mechanically ventilated patients.

L’obiettivo primario è quello di verificare gli effetti della dexmedetomina sull’attività neurologica diaframmatica (EAdi) nelle 24 ore successive all’inizio della terapia in pazienti in ventilazione meccanica che presentano difficoltà a discontinuare il supporto ventilatorio.

E.2.2

Secondary objectives of the trial

• to investigate effects of dexmedetomidine on other aspects of patient/ventilator interaction and respiratory pattern over 24 hours after starting study treatment; • to describe effects of dexmedetomidine on time to extubation, duration of mechanical ventilation and depth of sedation during the study; • to evaluate the safety of dexmedetomidine during the study.

• valutare gli effetti della dexmedetomina su altri aspetti delle interazioni ventilatorie del paziente e le sue capacità respiratorie nelle 24 ore successive all’inizio del trattamento in studio; • valutare gli effetti della dexmedetomina sul tempo necessario per discontinuare la ventilazione meccanica, la durata della ventilazione stessa e la profondità della sedazione richiesta durante la studio; • valutare la sicurezza del trattamento con dexmedetomina durante lo studio;

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

•Written informed consent obtained from the patient. •18 years or older. •Patients who have failed one weaning trial. •Receiving propofol as a sole agent for continuous sedation (minimum 12 hours) with target sedation level Richmond Agitation-Sedation Scale (RASS) +1 to -2 (must be in target at randomisation). •Intubated and mechanically ventilated in the ICU for more than 24 hours. •Patient has nasogastric (NG)/feeding tube in-situ.

•Consenso informato scritto ottenuto dal paziente. •Età maggiore od uguale a 18 anni. •Pazienti che hanno fallito un tentativo di discontinuazione della ventilazione assistita. •Pazienti che ricevono propofol come unico agente per una sedazione continua (minimo 12ore) con un livello di sedazione secondo la Richmond Agitation-Sedation Scale (RASS) da +1 a -2 (il livello target deve essere rispettato alla randomizzazione). •Pazienti intubati e ventilali meccanicamente in terapia intensiva da più di 24 ore. •Pazienti con sondino naso-gastrico (NG) in situ.

E.4

Principal exclusion criteria

•Patients who have failed more than one weaning trial. •Acute severe intracranial or spinal neurological disorder due to vascular causes, infection, intracranial expansion or injury. •Uncompensated acute circulatory failure at the time of randomisation (severe hypotension with mean arterial pressure less than 55 mmHg despite volume and vasopressors). •Severe bradycardia (heart rate [HR] less than 50 bpm). •AV conduction block II-III (unless pacemaker installed). •Unstable angina or acute myocardial infarction. •Severe hepatic impairment (bilirubin more than 101 mol/l). •Need for muscle relaxation at the time of randomisation (could only be used for intubation and initial stabilisation). •Acute renal failure requiring dialytic treatment of all types. •Pregnancy or breastfeeding. •Patients with tracheostomy. •Use of centrally acting alpha-2 agonists or antagonists (e.g. clonidine, titzanidine, apraclonidine and brimonidine) within 24 hours prior to randomisation. •Patients expected to have treatment withdrawn or withheld due to poor prognosis. •Patients unlikely to be weaned from mechanical ventilation; e.g. diseases/injuries primarily affecting the neuromuscular function of the respiratory apparatus such as clearly irreversible disease requiring prolonged ventilatory support (e.g. high spinal cord injury or amyotrophic lateral sclerosis). •Received any investigational drug within the preceding 30 days. •Concurrent participation in any other interventional study (any study in which patients are allocated to different treatment groups and/or non-routine diagnostic or monitoring procedures are performed). •Previous participation in this study. •Any other condition which, in the investigator’s opinion, could make it detrimental for the patient to participate in the study.

•Pazienti che hanno fallito più di un tentativo di discontinuazione della ventilazione assistita. •Complicanze neurologiche acute gravi intracraniche o spinali, dovute a cause vascolari, processi infettivi, versamenti intracranici o traumi. •Insufficenza circolatoria acuta scompensata alla randomizzazione (ipotensione grave con pressione arteriosa media < 55 mmHg indipendentemente dalla volemia e dai vasocostrittori o frazione di eiezione ventricolare sinistra minore del 30%). •Bradicardia severa (frequenza cardiaca [FC] < 50bpm). •Blocco II-III di conduzione AV, con l’eccezione della presenza di un pacemaker. •Angina instabile o infarto miocardico acuto. •Insufficenza epatica grave (Child-Pugh, classe C). •Necessità di miorilassanti al momento della randomizzazione (permessa soltanto per l’intubazione e per durante la stabilizzazione iniziale •Insufficenza renale acuta che necessiti di un qualsiasi trattamento dialitico. •Gravidanza o allattamento. •Pazienti tracheotomizzazti. •Somministrazione di alfa-2 agonisti o antagonisti (per es. Clonidina, tizanidina, apraclonidina e brimodinina) nelle 24 ore precedent la randomizzazione. •Pazienti per i quali si potrebbe attandere una sospensione del trattamento o un peggioramento della prognosi. •Pazienti per i quali è improbabile una sospensione della ventilazione meccanica, per es. lesioni traumatiche che colpiscono la funzionalità neuromuscolare dell’apparato respiratorio come le condizioni chiaramente irreversibili che necessitano un supporto ventilatorio prolungato (lesioni spinali alte, sclerosi laterale amiotrofica •Pazienti trattati con un farmaco sperimentale nei precedenti 30 giorni. •Partecipazione concomitante ad altri studi interventistici (qualsiasi studio nel quale il paziente è allocato ad un particolare gruppo di trattamento e/o nel quale si eseguono procedure diagnostiche e di monitoraggio non routinarie). •Parcepazione precedente a questo studio. •Qualsiasi condizione che a giudizio dell’Investigatore può compromettere la partecipazione del paziente a questo studio.

E.5 End points

E.5.1

Primary end point(s)

Asynchrony index (AI), defined as the total number of asynchronies as a proportion of the total number of respiratory efforts.

Asynchrony index (AI), definito come il numero totale di asincronismi, come la proporzione del numero totale degli sforzi respiratori.

E.5.1.1

Timepoint(s) of evaluation of this end point

0.5, 1, 2, 6, 12, 18 and 24 hours after starting study treatment.

0.5, 1, 2, 6, 12, 18 e 24 ore dopo l'inizio del trattamento.

E.5.2

Secondary end point(s)

- Other neural parameters; - Respiratory parameters; - Aterial blood gases; - Time to extubation; - Duration of mechanical ventilation; - Sedation variables; - Use of opioids; - Duration of ICU stay

• Parametri neurologici; • Parametri respiratori; • Emogasanalisi arteriosa; • Tempo di estubazione; • Durata della ventilazione meccanica; • Parametri di sedazione. • Utilizzo di oppioidi. • Durata della permanenza in terapia intensiva

E.5.2.1

Timepoint(s) of evaluation of this end point

0.5, 1, 2, 6, 12, 18 and 24 hours after randomisation or as appropriate

0.5, 1, 2, 6, 12, 18 e 24 ore dopo la randomizzazione o come appriopriato

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

Yes

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

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

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

last visit of te last subject (LVLS)

ultima visita ultimo soggetto

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

Number of subjects for this age range:

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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2012-03-12.

Yes

F.3.3.2

Women of child-bearing potential using contraception

Yes

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)

Normal treatment

Trattamento standard

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

2012-04-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-02-16

P. End of Trial
P.	End of Trial Status	Completed

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials