Clinical Trials Register

Summary
EudraCT Number:	2017-005180-40
Sponsor's Protocol Code Number:	Protocol_PPB_TKA_31122017
National Competent Authority:	Denmark - DHMA
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2018-01-08
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

Denmark - DHMA

A.2

EudraCT number

2017-005180-40

A.3

Full title of the trial

The effect of the popliteal plexus block on postoperative pain after total knee arthroplasty - a randomized, controlled, double-blinded study

Effekten af plexus popliteus blokade på postoperative smerter efter total knæalloplastik – et randomiseret, kontrolleret, dobbeltblindet studie

A.3.1

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

The effect of a new technique for anesthetizing the nerves involved in pain after knee replacement

Effekten af en ny teknik til at bedøve de nerver, som er involveret i smerter efter indsættelse af kunstigt knæled

A.4.1

Sponsor's protocol code number

Protocol_PPB_TKA_31122017

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.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	Operation og Intensiv Nord
B.5.3	Address:
B.5.3.1	Street Address	Nørrebrogade 44, Bygning 21, 1. sal
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	Marcain-adrenaline
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-adrenaline 5 mg/ml + 5 mikrogram/ml
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.3.9.3	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.3.9.1	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.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	Dexamethasone
D.2.1.1.2	Name of the Marketing Authorisation holder	KRKA
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	Dexamethasone
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.3.9.3	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	4.37
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	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

Postoperative posterior pain after total knee arthroplasty

Postoperativ posterior smerte efter total knæalloplastik

E.1.1.1

Medical condition in easily understood language

Pain after total knee replacement

Smerter efter indsættelse af kunstigt knæled

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	20.0
E.1.2	Level	PT
E.1.2	Classification code	10023469
E.1.2	Term	Knee arthroplasty
E.1.2	System Organ Class	10042613 - Surgical and medical procedures

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10002325
E.1.2	Term	Anesthesia local
E.1.2	System Organ Class	10042613 - Surgical and medical procedures

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10036236
E.1.2	Term	Postoperative pain relief
E.1.2	System Organ Class	10042613 - Surgical and medical procedures

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To assess the analgesic effect of the popliteal plexus block (PPB) as a supplement to a femoral triangle block (FTB) after total knee arthroplasty (TKA)

At undersøge den analgetiske effekt af plexus popliteus blokade som supplement til trigonum femoralis blokade efter total knæalloplastik

E.2.2

Secondary objectives of the trial

To evaluate the effect of the popliteal plexus block (PPB) in relation to opioid consumption, effect on sensory function and motor strength and to assess the onset time of the PPB. Furthermore, we aim to assess the number of patients who require a PBB as a supplement to a FTB.

At undersøge effekten af plexus popliteus blokade på opioidforbrug, på sensorisk og motorisk funktion samt at vurdere anslagstiden af PPB. Desuden er formålet at evaluere andelen af patienter, der har brug for et PPB som supplement til FTB.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Male or female at least 50 years of age at screening
- Scheduled to undergo primary total knee arthroplasty in spinal anaesthesia
- Normal sensory function at the lateral part of the thigh and lower leg
- American Society of Anesthesiologists (ASA) physical status 1, 2, or 3
- Able to provide informed consent

- Alder ≥ 50 år
- Primær total knæalloplastik i spinalanæstesi
- ASA 1,2 eller 3
- Normal sensorisk funktion på lateralsiden af lår og underben
- Informeret samtykke

E.4

Principal exclusion criteria

- Unable to cooperate and follow the study protocol
- Communication problems
- Allergic towards any medical product administered in the study
- Diabetes requiring medical treatment
- Pregnancy (a pregnancy test will be conducted on all women of childbearing potential prior to inclusion in the study. A positive test result will result in exclusion from the study)
- Preoperative opioid treatment (dosed > once daily)

- Manglende evne til at samarbejde og følge protokollen
- Kommunikationsproblemer
- Allergi over for lægemidler som anvendes i undersøgelsen
- Behandlingskrævende diabetes
- Graviditet (Kvinder i den fertile alder vil få foretaget en graviditetstest for inklusion og vil blive ekskluderet ved positivt resultat)
- Patienter i præoperativ opioid behandling (doseret > 1 gang dagligt)

E.5 End points

E.5.1

Primary end point(s)

Success of the PPB is defined as the proportion of patients with significant postoperative pain (NRS > 3) after FTB, who drop in pain score to NRS ≤ 3 after PPB and maintain NRS ≤ 3 without any opioids until 60 minutes after PPB.

PPB succes er defineret som andelen af patienter med signifikante postoperative smerter (NRS > 3) efter FTB, som falder i smertescore til NRS ≤ 3 efter PPB og opretholder NRS ≤ 3 uden opioider indtil 60 minutter efter PPB.

E.5.1.1

Timepoint(s) of evaluation of this end point

After placement of the PPB, pain scores (NRS) are registered every 5 minutes until 15 minutes after PPB placement. Pain scores are registered again 30 min, 45 min and 60 min after PPB.

Smertescore (NRS) registreres hvert 5. minut indtil 15 minutter efter PPB anlæggelse. Herefter registreres smertescore til tiderne 30 min, 45 min og 60 minutter efter PPB.

E.5.2

Secondary end point(s)

1) Onset time of the PPB (defined as the time from withdrawal of the block needle and until the patient reports NRS ≤ 3. Maximal onset time is defined as 60 min)
2) The effect of the PPB on cutaneous sensation on the lateral aspect of the lower leg (pinprick test)
3) The effect of PPB on isometric muscle strength of the dorso- and plantar flexors of the ankle joint (handheld dynamometer test)
4) Cumulated opioid consumption from 0-4 hours
5) Cumulated opioid consumption from 4-24 hours
6) Pain scores
7) Pain localization
8) The number of patients experiencing significant pain (NRS > 3) as a proportion of all patients with FTB

1) Anslagstid af PPB (anslagstid er defineret som tiden fra tilbagetrækning af nålen og indtil patienten rapporterer NRS ≤ 3. Maksimal anslagstid er per definition 60 min)
2) Effekten af PPB på sensorisk funktion på lateralsiden af crus (nålepriktest)
3) Effekten af PPB på isometrisk muskelstyrke af ankelleddets dorso- og plantarfleksorer (test med håndholdt dynamometer)
4) Kumuleret opioidforbrug fra 0-4 timer
5) Kumuleret opioidforbrug fra 4-24 timer
6) Smertescore
7) Smertelokalisering
8) Antallet af patienter som oplever signifikant smerte (NRS > 3) ud af alle patienter med FTB

E.5.2.1

Timepoint(s) of evaluation of this end point

1) Pain scores every 5 min until 15 min after PPB and then every 15 min until 60 min after PPB
2) Baseline and 2 hrs after PPB
3) Baseline and 2 hrs after PPB
4) 0-4 hrs, registered from the electronic patient record (EPJ)
5) 4-24 hrs, registered from the EPJ
6) For subjects receiving a PPB: 2, 4 and 24 hrs after PPB. For subjects not receiving a PPB: 24 hrs after the end of the primary observation period (POP)
7) NRS > 3: when significant pain is reported during POP; 15 and 60 min after PPB; at any increase in NRS score at any time during the 60 min after PPB; 2, 4 and 24 hrs after PPB.
NRS ≤ 3: at the follow-up visit 24 hrs after the end of the POP
8) POP: 3-hour period starting at the return of completely normal cutaneous sensation after spinal anesthesia.

1) Smertescore hvert 5. min indtil 15 min efter PPB og herefter hvert 15. min indtil 60 min efter PPB
2) Baseline og 2 timer efter PPB
3) Baseline og 2 timer efter PPB
4) 0-4 timer, registreret fra den elektroniske patientjournal (EPJ)
5) 4-24 timer, registreret fra EPJ
6) For patienter som modtager PPB: 2, 4 og 24 timer efter PPB. For patienter som ikke modtager PPB: 24 timer efter afslutningen af den primære observationsperiode (POP)
7) NRS > 3: når signifikant smerte rapporteres i løbet af POP; 15 og 60 min efter PPB; ved enhver stigning i NRS i løbet de første 60 min efter PPB; 2,4 og 24 timer efter PPB.
NRS ≤ 3: ved follow-up besøg 24 timer efter afslutning af POP
8) POP: 3-timers periode som starter ved komplet normalisering af sensorik efter spinalanæstesien.

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

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.6.13.1

Other scope of the trial description

The scope of the trial is to assess the effect of the popliteal plexus block (PPB) as a supplement to femoral triangle block (FTB). All patients will receive a FTB with 10 ml Marcain-adrenaline with the addition of 0.5 ml Dexamethasone. The FTB will cover the pain from the anterior part of the knee joint. Patients who despite FTB report NRS > 3 in the primary observation period will receive the study treatment: a PPB with either 10 ml Marcain-adrenaline or 10 ml saline according to randomization

Målet med studiet er at undersøge effekten af plexus popliteus blokade (PPB) som supplement til en trigonum femoralis blokade (FTB). Alle patienter får anlagt FTB med 10 ml Marcain-adrenalin tilsat 0.5 ml Dexamethason. FTB vil dække de anteriore knæsmerter. Patienter, som trods FTB rapporterer NRS > 3 i den primære observationsperiode, vil modtage forsøgsbehandlingen: PPB med enten 10 ml Marcain-adrenalin eller 10 ml saltvand i henhold til randomiseringen.

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

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

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

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

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial 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)

Patients will follow the standard of care after having completed the primary observation period defined as a 3-hour period starting at the return of completely normal cutaneous sensation after spinal anesthesia. One follow-up visit will be conducted after 24 hours, and after that the patient has completed participation in the trial.

Patienterne vil følge afdelingens standardbehandling efter, at de har gennemført den primære observationsperiode, defineret som en 3-timers periode, der starter ved komplet normalisering af sensorik efter spinalanæstesien. Efter 24 timer foretages et opfølgende besøg, og herefter har patienten afsluttet forsøget.

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

2018-02-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-02-05

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2018-08-23

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