Clinical Trials Register

Summary
EudraCT Number:	2018-001867-22
Sponsor's Protocol Code Number:	PRETIC
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2018-08-10
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

Spain - AEMPS

A.2

EudraCT number

2018-001867-22

A.3

Full title of the trial

TRANSFUSION OF RED BLOOD CELLS, TRANEXAMIC ACID AND FIBRINOGEN CONCENTRATE FOR SEVERE TRAUMA HEMORRHAGE AT PRE-HOSPITAL PHASE OF CARE. A PILOT TRIAL.

Estudio PILOTO sobre los efectos de la transfusión de concentrados de hematíes, ácido tranexámico y concentrado de fibrinógeno para el tratamiento de hemorragia secundaria a traumatismo grave en la fase de asistencia pre-hospitalaria

A.3.1

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

Evaluate treatment with red blood cells, tranexamic acid and in patients with hemorrhage due to severe trauma in patients in pre-hospital phase of care

Evaluar el tratamiento con concentrado de hematies, ácido tranexámico y fibrinógeno en pacientes con hemorràgia secundaria a traumatismo severo en la fase de tratamiento prehospitalària.

A.3.2

Name or abbreviated title of the trial where available

PRETIC

A.4.1

Sponsor's protocol code number

PRETIC

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	Banc de Sang i teixits
B.1.3.4	Country	Spain
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	Banc de Sang i Teixits
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Banc de Sang i Teixits
B.5.2	Functional name of contact point	Investigator
B.5.3	Address:
B.5.3.1	Street Address	Hosp Dr Josep Trueta,Avda França S/N,Pavello de Govern,Planta 3 despacho 330
B.5.3.2	Town/ city	Girona
B.5.3.3	Post code	17007
B.5.3.4	Country	Spain
B.5.4	Telephone number	00349729402002343
B.5.5	Fax number	0034972485422
B.5.6	E-mail	cmartinez@idibgi.org

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	RIASTAP
D.2.1.1.2	Name of the Marketing Authorisation holder	CSL Behring GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	RIASTAP
D.3.4	Pharmaceutical form	Powder 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.3.8	INN - Proposed INN	Human fibrinogen
D.3.9.1	CAS number	9001-32-5
D.3.9.2	Current sponsor code	FC
D.3.9.3	Other descriptive name	FIBRINOGEN CONCENTRATE
D.3.9.4	EV Substance Code	SUB127282
D.3.10	Strength
D.3.10.1	Concentration unit	g gram(s)
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	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	AMCHAFIBRIN
D.2.1.1.2	Name of the Marketing Authorisation holder	Mylan N.V, Netherland
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	TRANEXAMIC ACID
D.3.2	Product code	TXA
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	TRANEXAMIC ACID
D.3.9.1	CAS number	1197-18-8
D.3.9.2	Current sponsor code	TXA
D.3.9.3	Other descriptive name	TRANEXAMIC ACID
D.3.9.4	EV Substance Code	SUB11214MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1000
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

TREATMENT OF SEVERE TRAUMA HEMORRHAGE AT PRE-HOSPITAL PHASE OF CARE.

TRATAMIENTO DE LA HEMORRAGIA SECUNDARIA A TRAUMATISMO SEVERO EN LA FASE DE ATENCIÓN PRE-HOSPITALARIA.

E.1.1.1

Medical condition in easily understood language

TREATMENT OF HEMORRHAGE SECONDARY TO SEVERE TRAUMA

TRATAMIENTO DE LA HEMORRAGIA SECUNDARIA A TRAUMATISMO SEVERO

E.1.1.2

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutic techniques [E02]

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	10019524
E.1.2	Term	Hemorrhage
E.1.2	System Organ Class	100000004866

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

•Percentage of RBC returned or confirmed to be transfused compared to RBC delivered at the Sistema d'Emergències Mèdiques (SEM) units H2, G500 and G409.
•Percentage of RBC conserved at SEM emergency units (H2, G500 and G409) above 6ºC or less than 2ºC.
•Compare TEG6s® parameters that define TIC (R-CK, MA-CFF, MA-CRT and Ly30-CRT) between pre-hospital blood sample and hospital admission blood sample and between control and experimental groups.
•Compare all-cause mortality between control and experimental groups at 1, 6 and 24 hours of hospital admittance.

oPorcentaje de CH retornados o confirmados de ser transfundidos comparados con los entregados a las unidades (H2, G500 y G409) del Sistema de Emergencias Médicas (SEM).
oPorcentaje de los CH conservados en las unidades SEM (H2, G500 y G409) del SEM a >6ºC y <2ºC.
oComparar los parámetros de coagulación que nos ofrece el test viscoelástico TEG6s(R) (R-CK; MA-CFF, MA-CRT y Ly30-CRT) entre las muestras extraídas en el ámbito pre-hospitalario antes de la administración de cualquier tratamiento y la muestra extraída a la admisión al servicio de urgencias del Hospital Universitari de Girona Dr. Josep Trueta entre el mismo grupo y entre grupos experimental y control.
oComparar la mortalidad por cualquier causa entre les grupos control y experimental a 1, 6 i 24h del ingreso hospitalario

E.2.2

Secondary objectives of the trial

•Compare all-cause mortality between control and experimental groups at 48 hours, 30 days and at hospital discharge.
•Compare transfusion adverse reactions between the two groups.
•Compare thromboembolism events between the two groups.
•Compare crystalloid fluid requirements between the two groups at emergency room discharge.
•Compare transfusion requirements of RBC, platelets and plasma at emergency room discharge, at 30 days and hospital discharge.
•Compare Intensive Care Unit (ICU) and Hospital length stay between the two groups.
•Compare ventilator-free days in ICU between the two groups.
•Compare water balance at 24 and 72h of ICU stay.

•Comparar la mortalidad por cualquier causa entre los grupos control y experimental a les 48h y los 30 días.
•Comparar las reacciones transfusionales entre ambos grupos.
•Comparar los eventos tromboembólicos entre ambos grupos.
•Comparar los requerimientos de fluidos de reposición cristaloides entre ambos grupos.
•Comparar los requerimientos transfusionales de CH, plaquetas y plasma durante toda la estancia hospitalaria entre ambos grupos.
•Comparar la estancia al servicio de cuidados intensivos (UCI) y la estancia hospitalaria total entre ambos grupos.
•Comparar los días libres de ventilación mecánica en la UCI entre ambos grupos.
• Comparar el balance hídrico a las 24 y 72h de estancia en la UCI.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

oAge ≥18 years AND
oPatients with severe trauma categorized as priority 0 or 1 according to the CatSalut Polytrauma Code (PPT) AND
oEvidence of bleeding or a high bleeding suspicion according to physician judgment OR
oPredicted to need transfusion according to TICCS score > 10.

•Edad > o = a 18 años Y
•Pacientes con traumatismo severo categorizados de prioridad 0 o 1 según el código PPT del CatSalut Y
•Evidencia de sangrado o alta sospecha de sangrado a juicio clínico O
•Previsión de necesidad de transfusión según escala TICCS > o = a 10.

E.4

Principal exclusion criteria

oMoribund patient with devastating injuries and expected to die within 1-hour OR
oKnown objection to blood components transfusion OR
oKnown acquired or congenital coagulopathies not related to the actual trauma OR
oKnown anticoagulant treatment (vitamin K antagonist, dabigatran, rivaroxaban, apixaban) OR
oKnown Pregnancy OR
oSevere isolated traumatic brain injury OR
oHemorrhage not related to the actual trauma.

•Paciente moribundo o con esperanza de vida <1h O
•Objeción conocida de transfusión de componentes sanguíneos O
•Coagulopatia congénita o adquirida conocida no relacionada con el traumatismo actual O
•Tratamiento anticoagulante conocido O
•Embarazo conocido O
•Traumatismo craneoencefálico aislado O
•Hemorrágia no relacionada con el traumatismo actual.

E.5 End points

E.5.1

Primary end point(s)

•Compare TEG6s® parameters that define TIC (R-CK, MA-CFF, MA-CRT and Ly30-CRT) between pre-hospital blood sample and hospital admission blood sample and between control and experimental groups.
•Compare all-cause mortality between control and experimental groups at 1, 6 and 24 hours of hospital admittance.

oComparar los parámetros de coagulación que nos ofrece el test viscoelástico TEG6s(R) (R-CK; MA-CFF, MA-CRT y Ly30-CRT) entre las muestras extraídas en el ámbito pre-hospitalario antes de la administración de cualquier tratamiento y la muestra extraída a la admisión al servicio de urgencias del Hospital Universitari de Girona Dr. Josep Trueta entre el mismo grupo y entre grupos experimental y control.
oComparar la mortalidad por cualquier causa entre les grupos control y experimental a 1, 6 i 24h del ingreso hospitalario

E.5.1.1

Timepoint(s) of evaluation of this end point

24 hours after inclusion in the study

24 horas tras inclusion en el estudio

E.5.2

Secondary end point(s)

• Compare all-cause mortality between control and experimental groups at 48 hours, 30 days and at hospital discharge.
• Compare transfusion adverse reactions between the two groups.
• Compare thromboembolism events between the two groups.
• Compare crystalloid fluid requirements between the two groups at emergency room discharge.
• Compare crystalloid fluid requirements between the two groups at the SEM units.
• Compare transfusion requirements of RBC, platelets and plasma at emergency room discharge, at 30 days and hospital discharge.
• Compare Intensive Care Unit (ICU) and Hospital length stay between the two groups.
• Compare ventilator-free days in ICU between the two groups.
• Compare water balance at 24 and 72h of ICU stay.

• Comparar la mortalidad por todas las causas entre los grupos control y experimental a las 48 horas, 30 días y al alta hospitalaria.
• Comparar las reacciones adversas transfusionales entre los dos grupos.
• Comparar los eventos de tromboembolismo entre los dos grupos.
• Compare los requerimientos de líquidos cristaloides entre los dos grupos en la descarga de la sala de emergencias.
• Comparar los requerimientos de transfusión de glóbulos rojos, plaquetas y plasma en el alta de la sala de emergencias, a los 30 días y el alta hospitalaria.
• Compare la Unidad de Cuidados Intensivos (UCI) y la estancia hospitalaria entre los dos grupos.
• Compare los días sin ventilación en la UCI entre los dos grupos.
• Compare el balance de agua a las 24 y 72 horas de estancia en la UCI.

E.5.2.1

Timepoint(s) of evaluation of this end point

30 days after inclusion

30 días tras inclusión en el estudio

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

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

La asignación se determina según las unidades SEM con disponibilidad de sangre, TXA y fibrinógeno

The experimental and control arms will be determined according to the SEM units with RBC, TXA and CF

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

clinica pratica habitual (ácido tranexámico y coloides)

standard clinical practice (tranexamid acid and colloids)

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

Study will end after last visit of last patient

El estudio finalizará tras la realización de la última visita del último paciente

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

Yes

F.3.3.1

Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2018-08-10.

Yes

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

Yes

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Patients with severe trauma

Pacientes con traumatismo severo

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)

There is no post trial follow up

No hay seguimiento posterior al ensayo

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

2018-09-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-08-30

P. End of Trial
P.	End of Trial Status	Completed

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