Clinical Trials Register

Summary
EudraCT Number:	2019-002438-35
Sponsor's Protocol Code Number:	860
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2019-06-25
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

Netherlands - Competent Authority

A.2

EudraCT number

2019-002438-35

A.3

Full title of the trial

Multiple doses versus single dose of cefazolin to prevent periprosthetic joint infection after revision arthroplasty: a multicenter open-label, randomized clinical trial.

Verlengde profylaxe versus enkele gift cefazoline ter preventie van gewrichtsprothese-infectie na revisie chirurgie: een multicentrisch gerandomiseerd onderzoek.

A.3.1

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

Comparison of long versus short antibiotic prophylaxis to prevent infection of the prosthesis of hip or knee after revision surgery.

Vergelijking van lange versus korte antibioticum behandeling ter voorkoming van postoperatieve infectie van de gewrichtsprothese.

A.3.2

Name or abbreviated title of the trial where available

REViSION

A.4.1

Sponsor's protocol code number

860

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	Radboudumc
B.1.3.4	Country	Netherlands
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	Radboudumc
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Radboudumc
B.5.2	Functional name of contact point	Clinical trials information
B.5.3	Address:
B.5.3.1	Street Address	Geert Grooteplein Zuid 10
B.5.3.2	Town/ city	Nijmegen
B.5.3.3	Post code	6525 GA
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	0031243614763
B.5.6	E-mail	sandra.eichelsheim@radboudumc.nl
B.Sponsor: 2
B.1.1	Name of Sponsor	Sint Maartenskliniek
B.1.3.4	Country	Netherlands
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	Radboudumc
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Sint Maartenskliniek
B.5.2	Functional name of contact point	Clinical trials information
B.5.3	Address:
B.5.3.1	Street Address	Hengstdal 3
B.5.3.2	Town/ city	Ubbergen
B.5.3.3	Post code	6574 NA
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	0031243659049
B.5.6	E-mail	onderzoeksverpleegkundige@maartenskliniek.nl

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	Kefzol
D.2.1.1.2	Name of the Marketing Authorisation holder	Eurocept International B.V.
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	Concentrate and solvent for solution for injection/infusion
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	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	kefzol
D.2.1.1.2	Name of the Marketing Authorisation holder	Eurocept International B.V.
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	Concentrate and solvent for solution for injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Auricular use 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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Prevention of periprosthetic joint infection on patients undergoing revision surgery of the hip or knee.

preventie van prothese infectie na revisie van de heup- of knieprothese

E.1.1.1

Medical condition in easily understood language

Prevention of infection after revision surgery of the prosthetic joint of the hip or knee

Voorkomen van infectie na re-operatie aan de heup- of knieprothese

E.1.1.2

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

MedDRA Classification

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	10057129
E.1.2	Term	Revision of total 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	10057128
E.1.2	Term	Revision of hip 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	PT
E.1.2	Classification code	10049924
E.1.2	Term	Infection prophylaxis
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	PT
E.1.2	Classification code	10064736
E.1.2	Term	Antibiotic prophylaxis
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

The primary objective is to investigate whether an extended regimen compared to a single dose of cefazolin is associated with an increased infection-free implant survival within one year after index revision arthroplasty of the hip or knee.

Primaire doel is onderzoeken of de verlengde profylaxe resulteert in verhoogd aantal infectie-vrij behouden van prothese binnen 1 jaar na revisie chirurgie

E.2.2

Secondary objectives of the trial

The secondary objectives include the determination of the incidence, risk factors, treatment outcome and prognosis of Surgical side infecion (SSI) and periprosthetic joint infectin (PJI) during follow-up. The safety and tolerance of the regimens, and the antimicrobial susceptibility patterns of microorganisms will be described. Patient reported outcome measures (PROMs) will be used to evaluate physical performance and satisfaction of subjects within 1 year after the index revision arthroplasty. A costutility analysis will only be performed when the primary outcome has demonstrated superiority of the extended regimen.

Secundaire uitkomstmaten zijn incidentie, risicofactoren, behandeluitkomsten en prognose van wondinfectie en prothese infectie tijdens follow-up. De veiligheid en tolerantie van de interventies, de gevoeligheid van de micro-organismen zullen beschreven worden. Patient reported outcome measures zullen gebruikt worden om de fysieke conditie en tevredenheid van de patienten te beoordelen. Een kosten-baten analyse wordt verricht als er superioriteit is van het verlengde regime.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Planned revision arthroplasty of the hip or knee prosthesis, with revision of one or more fixed components

Geplande revisie van knie of heupprothese, van 1 of meer vaste componenten

E.4

Principal exclusion criteria

Periprosthetic joint infection on baseline

prosthese infectie op baseline

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is the difference in proportion of infection-free implant survival between the study groups after 1 year of follow-up, as assessed by the independent Data Review Committee, in the mITT population.

Primaire eindpunt is het verschil in proportie van infectie-vrije behouden van implantaat tussen de 2 studiegroepen, na 1 jaar follow-up.

E.5.1.1

Timepoint(s) of evaluation of this end point

One year after revision arthroplasty

1 jaar na revisie operatie

E.5.2

Secondary end point(s)

a. The proportion of SSI and PJI in both study groups during follow-up.
b. The cefazolin susceptibility of the micro-organisms causing SSI and PJI in the study groups.
c. The number of repeated surgeries.
d. The reason for repeated surgery on the affected prosthetic joint during follow-up.
e. Adverse drug events and serious adverse events.
f. Risk factors associated with SSI and PJI.
g. PROMs at weeks 12 and 52

a. proportie wondinfecties en prothese-infecties in beide studiegroepen tijdens follow-up.
b. cefazoline gevoeligheid van micro-organismen die wondinfectie en prothese-infectie veroorzaken.
c. aantal heroperaties.
d. reden voor heroperaties aan geopereerde gewricht tijdens follow-up.
e. Adverse drug events en serious adverse events.
f. Risicofactoren geassocieerd met wondinfectie en prothese-infectie
g. patient reported outcome measures (PROMs) op baseline, week 12, 52

E.5.2.1

Timepoint(s) of evaluation of this end point

Within one year after revision arthroplasty

Binnen 1 jaar follow-up na revisie chirurgie

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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)

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

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:

250

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

530

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

780

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)

expected normal treatment of joint prosthesis by orthopedic surgeon

verwachte standaard zorg via orthopedisch chirurg.

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

2019-06-25

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-09-16

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

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