Clinical Trials Register

Summary
EudraCT Number:	2013-002078-30
Sponsor's Protocol Code Number:	REDNES06052013
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2013-07-11
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Belgium - FPS Health-DGM

A.2

EudraCT number

2013-002078-30

A.3

Full title of the trial

Acceleromyography and diaphragm electromyographic activity during neostigmine or sugammadex enhanced recovery from moderate residual neuromuscular blockade after rocuronium 0.6 mg kg-1: a double blind randomized study in anaesthetized healthy volunteers

A.3.1

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

Recovery of diaphragmatic function after muscle relaxation with a muscle relaxant used in anaesthesia: sugammadex compared with neostigmine, two different drugs that counteract muscle paralysis. A study in healthy, anaesthetized volunteers.

Onderzoek bij gezonde vrijwilligers onder anesthesie naar het hernemen van de normale werking van het middenrif na spierblokkade met een spierverslapper gebruikt tijdens anesthesie: sugammadex in vergelijking met neostigmine, twee verschillende geneesmiddelen die de spierverslapping tegengaan.

A.3.2

Name or abbreviated title of the trial where available

REcovery of Diaphragmatic function after NEuromuscular blockade and the role of Sugammadex (REDNES)

A.4.1

Sponsor's protocol code number

REDNES06052013

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	Onze-Lieve-Vrouw Ziekenhuis
B.1.3.4	Country	Belgium
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	Onze-Lieve-Vrouw Ziekenhuis Research Unit Anaesthesia&CCM
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Onze-Lieve-Vrouw Ziekenhuis
B.5.2	Functional name of contact point	Research Unit Anaesthesia&CCM
B.5.3	Address:
B.5.3.1	Street Address	Moorselbaan 164
B.5.3.2	Town/ city	Aalst
B.5.3.3	Post code	9300
B.5.3.4	Country	Belgium
B.5.4	Telephone number	32475200299
B.5.5	Fax number	3253781001
B.5.6	E-mail	bdesmedt@yucom.be

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	ROBINUL®-NEOSTIGMINE
D.2.1.1.2	Name of the Marketing Authorisation holder	EUMEDICA
D.2.1.2	Country which granted the Marketing Authorisation	Belgium
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
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
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	BRIDION
D.2.1.1.2	Name of the Marketing Authorisation holder	ORGANON
D.2.1.2	Country which granted the Marketing Authorisation	Belgium
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
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

We will compare usual care (neostigmine) with sugammadex for reversal of a moderate rocuronium-induced neuromuscular blockade and assess the effect on diaphragmatic EMG activity of sugammadex versus neostigmine.

E.1.1.1

Medical condition in easily understood language

Recovery of normal diaphragmatic function after neuromuscular blockade by a muscle relaxant often used during anaesthesia; sugammadex compared to neostigmine, two drugs counteracting muscle paralysis

Het hernemen van de normale werking van het middenrif na spierblokkade met een spierverslapper: sugammadex in vergelijking met neostigmine, twee geneesmiddelen die de spierverslapping tegengaan

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

Comparison of the effect on diaphragmatic EMG activity of sugammadex versus neostigmine.
To assess diaphragmatic activity, a transesophageal EMG recorder can be used, like the NAVA catheter (“Neurally Adjusted Ventilatory Assist”). Recent reports use the EMG signal obtained via a NAVA catheter during the weaning process as a marker for weaning failure. The reports link electromyographic activity of the diaphragm (Edi)-derived indices to the rapid shallow breathing index, a commonly used parameter to assess weaning outcome. We propose a double blind randomised trial in healthy volunteers, to assess the different effects of sugammadex and neostigmine on the central respiratory drive, neuromechanical coupling and diaphragm strength.

E.2.2

Secondary objectives of the trial

Assessment of the effect of neostigmine and sugammadex on the central respiratory drive and neuroventilatory efficiency, including diaphragmatic fatigue.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

A subject is only eligible and may enter the study, if all of the following criteria are met:
1. Only male, healthy volunteers will be enrolled after an in-depth interview
2. Each participant must have the mental capacity to decide whether he takes part in the trial or not. Each participant must voluntarily give his written informed consent.
3. Each participant must be between 18 and 35 (inclusive) years of age at the screening visit
4. Each participant must meet the American Society of Anaesthesiologists class I criteria.
5. Subject has a Body Mass Index (BMI) ≤ 26 kg/m2

E.4

Principal exclusion criteria

Volunteers may not have participated in a drug study within 90 days prior to dosing. A subject is ineligible and may not enter the study, if any of the following conditions are observed:
1. Known or suspected to have a neuromuscular disorder.
2. Use of medications known to interfere with NMBAs.
3. Known or suspected allergic reaction to sugammadex, neostigmine, rocuronium, anaesthetic or narcotic medications, or any drugs used during general anaesthesia.
4. Known or suspected to have an anatomical malformation impeding a proper intubation.
5. Family or personal history of problems related to anaesthesia.
6. Known or suspected to have a history of malignant hyperthermia.
7. Known to have a renal insufficiency.
8. Current smoker or history of smoking.
9. Drinking more than 2 consumptions of alcohol a day.
10. Known or suspected to have a chronic obstructive pulmonary disease GOLD classification 2 or higher.
11. Known to have an infection of the upper or lower airways, as diagnosed by clinical findings.
12. Reflux oesophagitis.

E.5 End points

E.5.1

Primary end point(s)

At the end of surgery when spontaneous breathing is resumed, good diaphragmatic function is essential. When faced with a certain degree of residual neuromuscular block (RNMB, or PostOperative Residual Curarization, PORC) anaesthetists nowadays have the option to choose between an acetylcholinesterase inhibitor (AchEI, e.g. neostigmine) or a selective relaxant binding agent (SRBA, sugammadex). Sugammadex can only be used with the steroidal neuromuscular blocking agents (NMBAs), like vecuronium and rocuronium.
A sugammadex dosage of 2 mg/kg is recommended in case of spontaneous recovery up to at least the reappearance of the second twitch of the train-of-four (TOF, T2) following a rocuronium induced blockade. The use of neostigmine 70µg/kg on reappearance of the second TOF response, was described by Kirkegaard and colleagues.
Our hypothesis is that by making nicotinergic acetylcholine receptors fee from rocuronium in the diaphragmatic neuromuscular junctions, instead of increasing the amount of acetylcholine, sugammadex will result in a better neuromuscular coupling at the moment of weaning from the ventilator compared to neostigmine. Recent studies have linked impaired neuromuscular efficiency to weaning failure in a critical care unit.
During weaning of the ventilator, after reversal of neuromuscular block with neostigmine or sugammadex, diaphragm electromyographic activity (Edi, obtained from the NAVA catheter), airway pressure and flow are acquired at 100 Hz from the ventilator via an interface connected to a computer using commercially available software (Maquet Critical Care, Solna, Sweden). The parameters derived from these devices are the following:
 EdiMAX.
 ΔEdi (max/min).
 EdiAUC (area under the curve).
 EdiMAX/tidal volume (TV).
 ΔEdi/TV.
 EdiAUC/TV.
 High-to-low frequency ratio.
 Centroid frequency.
These last two values are of interest when assessing diaphragmatic fatigue.
 AEs will be recorded.

E.5.1.1

Timepoint(s) of evaluation of this end point

After induction of anaesthesia and muscle relaxant administration, spontaneous recovery is allowed to progress until the re-appearance of the second twitch on the train-of-four (TOF) monitor (acceleromyography of the thumb). The volunteers will then receive either sugammadex or neostigmine. Upon full recovery of neuromuscular block, as defined by three measurements of TOF ≥90% of baseline, the ventilator minute volume will be reduced by 50% (ventilator frequency divided by two). When spontaneous breathing effort is noticed, either by the diaphragm-EMG catheter (NAVA catheter) or the ventilator, the subject's ventilation mode will be switched to spontaneous ventilation and sedation stopped. Throughout this period of weaning, the above parameters will be registered continuously.

E.5.2

Secondary end point(s)

Adverse Events will be recorded.

E.5.2.1

Timepoint(s) of evaluation of this end point

Throughout the procedure.

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)

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

Yes

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:

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

Yes

F.3.2

Patients

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.

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

2013-07-29

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-08-08

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

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