Clinical Trials Register

Summary
EudraCT Number:	2011-002287-24
Sponsor's Protocol Code Number:	201105-RCTTEG
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2011-12-20
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

2011-002287-24

A.3

Full title of the trial

Massive blood loss in children during multiple trauma or major surgery:
Fibrinogen therapy for massive blood loss during elective surgery for craniosynostosis repair, a double blinded randomized controlled study

Toepassing van fibrinogeen therapie bij kinderen voor massaal bloedverlies tijdens craniosynostosis chirurgie, een dubbel blind gerandomiseerd onderzoek

A.3.1

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

Fibrinogen therapy for massive blood loss in children

Fibrinogeen behandeling voor massaal bloedverlies bij kinderen

A.3.2

Name or abbreviated title of the trial where available

RCT TEG

A.4.1

Sponsor's protocol code number

201105-RCTTEG

A.5.4

Other Identifiers

Name:

Nederlands Trial Register

Number:

NTR2975

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	Erasmus MC
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	Erasmus MC
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	Erasmus MC
B.5.2	Functional name of contact point	Inge Appel
B.5.3	Address:
B.5.3.1	Street Address	Dr. Molewaterplein 60
B.5.3.2	Town/ city	Rotterdam
B.5.3.3	Post code	3015 GJ
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	31107036691
B.5.5	Fax number	31107036801
B.5.6	E-mail	i.m.appel@erasmusmc.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	Haemocomplettan P
D.2.1.1.2	Name of the Marketing Authorisation holder	CSL Behring GmbH
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	Powder and solution for 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.3.9.1	CAS number	9001-32-5
D.3.9.3	Other descriptive name	HUMAN FIBRINOGEN
D.3.9.4	EV Substance Code	SUB12502MIG
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	60
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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	NaCl 0,9%
D.2.1.1.2	Name of the Marketing Authorisation holder	B. Braun Avitum AG
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Sodium Chloride 0,9%
D.3.4	Pharmaceutical form	Solution for 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.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	Solvent for solution for infusion
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

massive blood loss in surgery for premature fusion of cranial sutures, massive blood loss in fused bones of the skull

massaal bloedverlies bij chirurgie voor voortijdige vergroeing van schedelnaden, massaal bloedverlies bij de operatie voor aan elkaar groeien van schedelnaden

E.1.1.1

Medical condition in easily understood language

massive blood loss

massaal bloedverlies

E.1.1.2

Therapeutic area

Diseases [C] - Blood and lymphatic diseases [C15]

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	10005645
E.1.2	Term	Blood loss of (NOS)
E.1.2	System Organ Class	100000004866

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective is to investigate whether the volume of infused blood products can be reduced, in children undergoing elective craniosynostosis surgery, using fibrinogen infusion at the start of the operative procedure compared to a placebo-control arm.

Het primaire doel van ons onderzoek is om in een gerandomiseerd, gecontroleerd dubbel-blind onderzoek aan te tonen dat de kinderen die met fibrinogeen concentraat (Haemocomplettan P®) worden behandeld minder bloedtransfusies nodig zullen hebben dan de kinderen die met de placebo NaCl 0.9% worden behandeld. (zie pagina 9 en 10)

E.2.2

Secondary objectives of the trial

Secondary objectives include the following parameters:
- blood loss in ml
- duration of the operation time,
- the number of hours of post-operative intensive care admission
- duration of total hospital stay
- postoperative complications such as thromboembolic events or wound infections.
- the safety of fibrinogen infusion in this patient group
- monitoring of coagulation parameters including TEG

Het tweede doel van dit onderzoek zal de mate van bloedverlies, de duur van de operatie en postoperatieve complicaties inventariseren, alsmede de veiligheid van de studiemedicatie. (zie pagina 9 en 10) M.b.v monitoring met thromboelastografie 'aan het bed' zal blijken dat snellere interventie tijdens een operatie mogelijk is, waardoor uiteindelijk minder bloedverlies en dus minder transfusie behoefte zal ontstaan. Uiteindelijk zullen de uitkomsten van waarde zijn voor verdere geprotocolleerde diagnostiek en behandeling van elk massaal bloedverlies op de kinderleeftijd.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- primary non-syndromic craniosynostosis undergoing elective repair
- written informed consent
- age older than 5 months and younger than 25 months

- kinderen die in aanmerking komen voor chirurgie voor een niet-syndromale craniosynostose
- getekend toestemmingsformulier
- leeftijd tussen 5 en jonger dan 25 maanden

E.4

Principal exclusion criteria

- the presence of congenital bleeding diathesis or congenital prothrombotic risk factors like protein C or S deficiency or antithrombin deficiency. (Congenital Factor F Leiden and the prothrombin F II mutation are no contraindication for surgery).
- known hypersensitivity against Haemocomplettan P®
- known coagulopathy
- presence of a craniofacial malformation syndrome.
- active infectious disease
- patients with anemia or thrombocytopenia before the surgical intervention
- patients with prior thrombo-embolic disease

- stollingsstoornis hebben
- overgevoeligheid voor Haemomplettan P®
- craniosynostose als onderdeel van een syndromale afwijking
- anemie
- thrombose

E.5 End points

E.5.1

Primary end point(s)

Primary outcome measure is the amount of transfused blood products in ml.

Hoeveelheid aan bloedtransfusies in ml

E.5.1.1

Timepoint(s) of evaluation of this end point

after 72 hours

na 72 uur

E.5.2

Secondary end point(s)

Secondary study parameters are:
- duration of the operation time,
- the number of hours of post-operative intensive care admission
- duration of total hospital stay
- postoperative complications such as thrombo-embolic events or wound infections the next 2 days.
- the safety of fibrinogen infusion in this patient group according to chills, fever, nausea and vomiting, allergic reactions and thrombo-embolic complications during and after surgery. Total observation will amount 72 hours, in case of an adverse event patient will be followed until resolution of the problem.
- monitoring of coagulation parameters including TEG at fixed time points (see section 7.3.2)

Secundaire eindpunten:
- de duur van de operatie,
- aantal uren postoperatieve hospitalisatie,
- duur van de total hospitalisatie,
- complicaties inventariseren, alsmdede de veiligheid van de studiemedicatie. (zie pagina 9 en 10)
M.b.v monitoring met thromboelastografie 'aan het bed' zal blijken dat snellere interventie tijdens een operatie mogelijk is, waardoor uiteindelijk minder bloedverlies en dus minder transfusie behoefte zal ontstaan. Uiteindelijk zullen de uitkomsten van waarde zijn voor verdere geprotocolleerde diagnostiek en behandeling van elk massaal bloedverlies op de kinderleeftijd.

E.5.2.1

Timepoint(s) of evaluation of this end point

after 72 hours

na 72 uur

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

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)

Yes

E.7.4

Therapeutic use (Phase IV)

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

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

last patient last visit

laatste patiënt laatste visite

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

Yes

F.1.1

Number of subjects for this age range:

120

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)

Yes

F.1.1.4.1

Number of subjects for this age range:

110

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

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

Yes

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Consent will be given by parents or legal guardian

Toestemming zal worden gegeven door ouders of wettelijke vertegenwoordigers

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

120

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)

not applicable

niet van toepassing

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

2011-12-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-07-11

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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