Clinical Trials Register

Summary
EudraCT Number:	2018-002961-21
Sponsor's Protocol Code Number:	NS918
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:	2018-09-21
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

Belgium - FPS Health-DGM

A.2

EudraCT number

2018-002961-21

A.3

Full title of the trial

The effect of deep neuromuscular block and reversal with sugammadex on surgical conditions and perioperative morbidity in shoulder surgery using a deltopectoral approach

A.3.1

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

The effect of deep relaxation on surgical conditions and morbidity in shoulder surgery

A.4.1

Sponsor's protocol code number

NS918

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT03643913

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	UZ Leuven
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	MSD
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	UZ Leuven
B.5.2	Functional name of contact point	Clinical Trial Assistant
B.5.3	Address:
B.5.3.1	Street Address	Herestraat 49
B.5.3.2	Town/ city	Leuven
B.5.3.3	Post code	3000
B.5.3.4	Country	Belgium
B.5.4	Telephone number	321634 23 64
B.5.6	E-mail	traumatologie@uzleuven.be

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	Esmeron
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Sharp & Dohme B.V. Waarderweg 39 2031 BN Haarlem, The Netherlands
D.2.1.2	Country which granted the Marketing Authorisation	Netherlands
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Rocuronium Bromide
D.3.9.1	CAS number	119302-91-9
D.3.9.2	Current sponsor code	MK-8085
D.3.9.3	Other descriptive name	ROCURONIUM BROMIDE
D.3.9.4	EV Substance Code	SUB10353MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/kg/h milligram(s)/kilogram/hour
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	0.075 to 0.1
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	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	Merck Sharp & Dohme B.V. Waarderweg 39 2031 BN Haarlem, The Netherlands
D.2.1.2	Country which granted the Marketing Authorisation	Netherlands
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 bolus use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Sugammadex Sodium
D.3.9.1	CAS number	343306-79-6
D.3.9.2	Current sponsor code	MK-8616
D.3.9.3	Other descriptive name	SUGAMMADEX SODIUM
D.3.9.4	EV Substance Code	SUB32205
D.3.10	Strength
D.3.10.1	Concentration unit	mg/kg milligram(s)/kilogram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2
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

Subject undergoing elective or semi-elective surgery to the gleno-humeral joint or the proximal humerus using a deltoideo-pectoral approach.

E.1.1.1

Medical condition in easily understood language

Patient undergoing a planned surgery to the shoulder joint or upperarm, where the surgeon makes an incision at the border of the shoulder muscle and chest muscle.

E.1.1.2

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Surgical Procedures, Operative [E04]

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

The study evaluates whether deep neuromuscular block during entire surgical procedure to the gleno-humeral joint or the proximal humerus using a deltoideo-pectoral approach results in less muscular damage to the deltoid muscle and therefore less post-operative pain and an earlier functional recovery. The main objective consists of better view and access to the gleno-humeral joint and/or proximal humerus and a decreased early post-operative pain due to less surgical injury to the deltoid muscle.

E.2.2

Secondary objectives of the trial

• Less deltoid muscle injury (subjectively scored and documented by photographic images)
• Less post-operative pain as per analgesia use
• Shorter length of stay
• Shorter surgical procedure
• Evaluate the efficacy of “dry catheter” technique (interscalene block (ISB) using only catheter without initial dose of local anesthetic)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• 18 years or older at enrollment
• Subjects who are undergoing elective or semi-elective surgery to the gleno-humeral joint or the proximal humerus using a deltoideo-pectoral approach

E.4

Principal exclusion criteria

• Inability to consent because of mental status
• Open injuries involving the deltoid muscle
• Previous open surgery on the shoulder joint
• American Society of Anesthesiologists (ASA) physical status > II
• Age < 18 or > 75 years old
• Body mass index (BMI) <18,5 or > 35 kg/m²
• Renal insufficiency: glomerular filtration rate < 40 ml/min
• Impaired liver function: hepatic cirrhosis, cholestatic jaundice
• Neuromuscular disease
• Pregnant female subjects
• Breastfeeding female subjects
• Patients receiving medications known to interact with neuromuscular blocking agents
• Allergy to any drug included in the anesthetic protocol

E.5 End points

E.5.1

Primary end point(s)

1. Modified Leiden score: An increase of 2 grades in modified Leiden score. The surgeon will be asked to score the surgical conditions on a five step scale based upon previously used scales:
grade 5: optimal surgical conditions, perfect access to the proximal humerus, glenohumeral joint and excellent visibility.
grade 4: good conditions: adequate surgical conditions to perform the surgery, but not optimal
grade 3: acceptable conditions, surgical procedure is jeopardized, but adequate surgical result is obtained, eventually after additional intervention
grade 2: poor conditions, exposure and handling hindered resulting in suboptimal surgical outcome
grade 1: extremely poor conditions, the surgeon is unable to work because of the inability to get access to the shoulder joint because of inadequate muscle relaxation.
2. Decrease in early post-operative pain scored with visual analogue scale (VAS): Scale ranges from 0 to 10 representing respectively no pain and worst imaginable pain.

E.5.1.1

Timepoint(s) of evaluation of this end point

1. 1 day of surgery
2. day 3 post-operative at 14 o' clock

E.5.2

Secondary end point(s)

1. Decrease in score for muscle damage: After the surgical procedure the surgeon will be asked to score the deltoid muscle damage. Two light photos will be taken before closure of the deltoideopectoral interval to document the muscular damage. The usage of two light photos allows to measure the mean of the grades. At the end of the study, a second reading and scoring of the damage based upon the light photos will be performed by two independent reviewers (surgeons blinded to the procedure).
• grade 1: no muscular damage
• grade 2: superficial damage (fraying) or contusion
• grade 3: muscular tear < 1cm depth
• grade 4: muscular tear > 1cm depth
2. Decrease in VAS and analgesic needs: Post-operative pain will be scored using a VAS-pain scale ranging from 0 (no pain) to 10 (worst imaginable pain). VAS recording until 30 days post-operative. The analgesic needs of the patient during hospitalization will be derived from the Electronic Medical Prescription (EMV) module of the Electronic patient file system of the University Hospitals Leuven, klinisch werkstation (KWS). The scoring will be done at 8-14 and 20 o’clock on days 1-3-5 post-operative at the bedside of the patient by the nurse using a VAS. If the patient is discharged from the hospital before the 5th day post-operative, this measurement will be performed by the patient in the diary. The analgesic needs of the patient during hospitalization will be derived from EMV module of the Electronic patient file system of the University Hospitals Leuven, KWS. The total morphine consumption will be assessed in all groups as well as rescue medication such as ketalar, NSAID’s catapressan and paracetamol.
3. Decrease in length of stay at post-anesthesia care unit (PACU): Evaluation and length of stay at the PACU will also be examined as this clearly reflects the amount of post-operative comfort or possible adverse effects witnessed post procedure. The parameter will be expressed in hours and there will be two measurements. The time of expected discharge and the actual discharge (with reasons of possible delay between those two figures expressed in minutes or hours).
4. Decrease of length of stay: Is defined as post-operative length of stay, the day of surgery being day 0. This parameter will be expressed in days. As post-operative pain is one of the principal reasons for hospitalization after shoulder surgery, we believe this parameter is an indirect measure for post-operative pain.
5. Decrease of lenght of surgery: Will be expressed in %. As different procedures are being performed within this study, absolute length would not be indicative for ease of procedure. Therefore we express length of surgery as actual length of the procedure (incision to closure), divided by the mean length of the 10 last identical procedures (out of the study) performed by the same surgeon.
6. Evaluation of Dry Catheter Technique: Evaluation of the efficacy of the catheter will be done 30 minutes after the bolus injection. Efficacy will be tested by using ether swab to test sensory block and also motorfunction evaluation of the motorjoint (raising arm to full height pass/fail).

E.5.2.1

Timepoint(s) of evaluation of this end point

1. Day of surgery by surgeon and at the end of the study by independent reviewers
2a. During hospitalisation: at 8-14 and 20 o’clock on days 1-3-5
2b. After discharge: up till 30 days post-operative
3. Day of surgery
4. From day 3 up to 3 weeks after surgery
5. Intraoperative
6. Day of surgery

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

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:

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

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

2018-10-18

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-11-09

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

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