Clinical Trials Register

Summary
EudraCT Number:	2014-004207-78
Sponsor's Protocol Code Number:	ProtokolSB1
National Competent Authority:	Denmark - DHMA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2014-11-19
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

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A. Protocol Information

A.1

Member State Concerned

Denmark - DHMA

A.2

EudraCT number

2014-004207-78

A.3

Full title of the trial

Comparison of the effect of saphenous block with plain bupivacaine vs. protracted bupivacaine mixture as a supplement to continuos sciatic catheter after major ankle and foot surgery: a randomized study

Sammenligning af effekten af saphenusblokade med bupivacain vs. protraheret bupivacainblanding som supplement til kontinuert ischiadicusblokade efter stor ankelkirurgi

A.3.1

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

Post-operative pain treatment of patients after major ankle and foot surgery by comparing a nerve block with plain local anesthetic to a new
protracted mixture of local anesthetics.

Smertedækning af patienter efter stor ankel- og fodkirurgi vha. sammenligning af nervebedøvelse med almindelig lokalbedøvelse i forhold til en ny længerevirkende lokalbedøvelsesblanding

A.4.1

Sponsor's protocol code number

ProtokolSB1

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	Aarhus University Hospital
B.1.3.4	Country	Denmark
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	A.P. Møller og Hustru Chastine Mc-Kinney Møllers Fond til almene Formaal
B.4.2	Country	Denmark
B.4.1	Name of organisation providing support	Grosserer L.F. Foghts fond
B.4.2	Country	Denmark
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Aarhus University Hospital
B.5.2	Functional name of contact point	Dep. Anaesthesia and Intensive Care
B.5.3	Address:
B.5.3.1	Street Address	Nørrebrogade 44, building 21
B.5.3.2	Town/ city	Aarhus C
B.5.3.3	Post code	8000
B.5.3.4	Country	Denmark
B.5.4	Telephone number	+4551542997
B.5.6	E-mail	tfb@dadlnet.dk

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	Dexagalen
D.2.1.1.2	Name of the Marketing Authorisation holder	GALENpharma GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Denmark
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	Dexagalen
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	Perineural use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	DEXAMETHASONE SODIUM PHOSPHATE
D.3.9.3	Other descriptive name	DEXAMETHASONE SODIUM PHOSPHATE
D.3.9.4	EV Substance Code	SUB01615MIG
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	4
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	Marcain-Adrenalin
D.2.1.1.2	Name of the Marketing Authorisation holder	AstraZeneca A/S
D.2.1.2	Country which granted the Marketing Authorisation	Denmark
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	Marcain-Adrenalin
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	Perineural use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	BUPIVACAINE HYDROCHLORIDE
D.3.9.3	Other descriptive name	BUPIVACAINE HYDROCHLORIDE
D.3.9.4	EV Substance Code	SUB00902MIG
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	EPINEPHRINE
D.3.9.1	CAS number	51-43-4
D.3.9.3	Other descriptive name	EPINEPHRINE
D.3.9.4	EV Substance Code	SUB06568MIG
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	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
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	Perineural use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Post-operative pain after three types of major ankle and hind foot surgery: (1) total ankle arthroplasty, (2) ankle arthrodesis or (3) subtalar arthrodesis

Postoperative smerter efter tre typer af stor ankel- og bagfodskirurgi: (1) ankelalloplastik, (2) ankelartrodese eller (3) subtaloartrodese.

E.1.1.1

Medical condition in easily understood language

Patients' pains after major ankle and foot surgery defined as a total ankle replacement or a fusion of the joint.

Patienternes smerter efter stor ankel- og bagfodskirurgi defineret som indsættelse af kunstigt ankelled eller stivgørende operation af leddet.

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	17.1
E.1.2	Level	LLT
E.1.2	Classification code	10003396
E.1.2	Term	Arthroplasty NOS
E.1.2	System Organ Class	100000004865

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.1
E.1.2	Level	LLT
E.1.2	Classification code	10016962
E.1.2	Term	Foot arthrodesis
E.1.2	System Organ Class	100000004865

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.1
E.1.2	Level	LLT
E.1.2	Classification code	10002540
E.1.2	Term	Ankle arthrodesis
E.1.2	System Organ Class	100000004865

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 main objective is to investigate whether addition of the adjuvant
dexamethasone to bupivacaine-adrenaline can prolong the analgesic
effect of the saphenous block compared to plain bupivacaine-adrenaline
in patients after major ankle and hind foot surgery.

Hovedformålet er at undersøge om tilsætning af dexamethason til bupivacain-adrenalin kan forlænge den analgetiske virkningsvarighed af saphenusblokaden i forhold til ren bupivacain-adrenalin hos patienter efter stor ankel- og bagfodskirurgi.

E.2.2

Secondary objectives of the trial

- Compare the cumulated opioid consumption during the first 48 hours after surgery
- Compare pain scores during the first 48 hours after surgery
- Investigate the localization of the pain during the first 48 hours after surgery

- Sammenligne det kumulerede opioidforbrug 48 timer postoperativt
- Sammenligne smertescore 48 timer postoperativt
- Undersøge lokalisering af smerter de første 48 timer postoperativt

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Elective ankle or hind foot surgery either (1) total ankle arthroplasty, (2) ankle arthrodesis or (3) subtalar arthrodesis
- Age ≥ 18
- ASA I-III
- Informed consent both orally and in writing after the patient has fully understood the protocol and its limitations.

- Elektiv bagfods- og/eller ankelkirurgi enten (1) ankelalloplastik eller (2) ankelartrodese (ikke-artroskopisk) eller (3) subtaloartrodese
- Alder ≥ 18 år
- ASA I-III
- Mundtligt og skriftligt informeret samtykke til deltagelse i undersøgelsen efter at have forstået protokollens indhold og begrænsninger fuldt ud

E.4

Principal exclusion criteria

- Communication problems or dementia
- Allergies to any medical product used in the study
- Neuropathy of the sciatic or femoral nerve prior to the operation
- Morbus Charcot-Marie-Tooth disease, diabetic neuropathy, peripheral vascular disease
- BMI > 35
- Pregnancy
- Daily use of opioids
- Coagulation disorders
- Infection at the site of injection or systemic infection

- Kommunikationsproblemer eller demens
- Allergi overfor lægemidler anvendt i undersøgelsen
- Præoperativ n. ischiadicus eller n. femoralis neuropati
- Præoperativ nedsat kraft eller sensorik i operationsekstremiteten
- Morbus Charcot-Marie-Tooth, diabetisk neuropati, svær perifer vaskulær sygdom
- BMI >35
- Graviditet
- Dagligt forbrug af opioider
- Koagulationsforstyrrelser
- Infektion sv.t. indstiksstedet eller systemisk infektion

E.5 End points

E.5.1

Primary end point(s)

Duration of the saphenous nerve block with plain vs. protracted
bupivacaine mixture registered as the time until the first dose of
morphine is taken, and when the pain score is above 3 and located to
the frontal or medial side of the ankle. Morphine is administered
intravenously by a patient controlled pump, (PCA - Patient Controlled
Analgesia), which will give a specific dose when the patient pushes the
button. The patients will be thoroughly instructed in the use of the pump prior to the operation and the importance of scoring their pain and indicating the localization if they want to take a dose of morphine is underlined.

Virkningsvarighed af n. saphenusblokade med plain vs. protraheret bupivacainblanding registreret som tiden indtil første dosis morfin, hvor patienten angiver smertescore større end numeric rating scale (NRS) score 3 og lokalisering af værste smerte til for- eller inderside af ankelleddet. Der anvendes intravenøs patientkontrolleret smertebehandling, Patient Controlled Analgesia (PCA), hvor patienten kobles til en smertepumpe med morfin, som indgiver en bestemt dosis, når patienten trykker på knappen. Patienterne instrueres før operationen grundigt i, hvornår de skal tage morfin og vigtigheden af, at de samtidig scorer deres smerter på NRS samt angiver lokaliseringen af smerterne.

E.5.1.1

Timepoint(s) of evaluation of this end point

The timepoint for the primary end point is the exact time where the first bolus of morphine is taken by the patient. This timepoint is registered by the PCA pump and will be within the first 48 hours after surgery.

Tidspunktet for evaluering af det primære effektmål er det præcise tidspunkt hvor patienten første gang tager en bolus morfin. Dette tidspunkt registreres af PCA pumpen og vil være indenfor de første 48 timer.

E.5.2

Secondary end point(s)

- Cumulated opioid consumption registered by the PCA pump
- Pain score on the NRS (Numeric ranking scale) with values from 0 to 10. Pain scoring is done at rest because the patient's leg is elevated on a Kirschner splint. It is the maximal pain since the last score, which is evaluated.
- Pain localization
- Test of sensory blockade of the peroneal, tiabial and saphenous nerve. The sensory blockade of the peroneal nerve is tested on the dorsal side
of the toes and the tibial nerve on the plantar side of the toes. The
saphenous territory at the medial side of the lower leg is covered in
a cast, and therefore the orthopaedist will make a small window in the
cast to enable testing.

- Kumuleret opioidforbrug ved PCA pumpe
- Smertescore med NRS med værdier fra 0 til 10, hvor 0 er ingen smerte og 10 er den værst tænkelige smerte. Smertescoring foretages i hvile, da patienten ligger med benet eleveret på Kirschnerskinne. Det er den maksimale smerte i perioden siden sidste scoring, som registreres.
- Smerternes lokalisering
- Test af sensorisk blokade af n. peroneus, n. tibialis og n. saphenus. Sensorisk blokade af n. peroneus testes med is på dorsalsiden af tæerne og tilsvarende testes n. tibialis på plantarsiden af tæerne. N. saphenus’ innervationsområde på medialsiden af crus er dækket af gipsbandagering, men ortopædkirurgerne laver et vindue i gipsen for at muliggøre sensorisk test af n. saphenus.

E.5.2.1

Timepoint(s) of evaluation of this end point

Cumulated opioid consumption is registered 48 hours after surgery
Pain score, pain localization and sensory tests are performed at regular time intervals: Arrival at and departure from the Perioperative Section and 6, 12, 24, 30, 36, 42 and 48 hours after surgery.

Kumuleret opioidforbrug registreres 48 timer efter operationen.
Smertescore, smertelokalisering samt sensorisk test foretages på følgende tidspunkter: Ankomst til samt afgang fra Perioperativt Afsnit og 6, 12, 24, 30, 36, 42 og 48 timer postoperativt.

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

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)

E.8.2.2

Placebo

Yes

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

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)

None

Ingen

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

2015-01-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-11-07

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2015-12-16

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