Clinical Trials Register

Summary
EudraCT Number:	2021-006870-22
Sponsor's Protocol Code Number:	1144/2022
National Competent Authority:	Austria - BASG
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2022-09-13
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

Austria - BASG

A.2

EudraCT number

2021-006870-22

A.3

Full title of the trial

Substitution of coagulation factors and blood products in patients with liver cirrhosis - A pilot study

Substitution von Gerinnungsprodukten bei Patienten mit Leberzirrhose - Eine Pilotstudie

A.3.1

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

Substitution of coagulation factors and blood products in patients with liver cirrhosis - A pilot study

Substitution von Gerinnungsprodukten bei Patienten mit Leberzirrhose - Eine Pilotstudie

A.3.2

Name or abbreviated title of the trial where available

COUCH - Coagulation in Cirrhosis

A.4.1

Sponsor's protocol code number

1144/2022

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	Medical University of Vienna
B.1.3.4	Country	Austria
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	Medical University of Vienna
B.4.2	Country	Austria
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Medical University of Vienna
B.5.2	Functional name of contact point	Department of Anaesthesia
B.5.3	Address:
B.5.3.1	Street Address	Währinger Gürtel 18-20
B.5.3.2	Town/ city	Vienna
B.5.3.3	Post code	1090
B.5.3.4	Country	Austria
B.5.4	Telephone number	+43140400 41000
B.5.5	Fax number	+43140400 40280
B.5.6	E-mail	armin.langauer@meduniwien.ac.at

D. IMP Identification
D.IMP: 1
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	- Cofact 500 IE (Prothya Biosolutions Netherlands B.V.)
D.2.1.1.2	Name of the Marketing Authorisation holder	Biotest Pharma GmbH D-63303 Dreieich
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	Cofact 500 IE
D.3.4	Pharmaceutical form	Powder and solvent for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Infusion (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PROTHROMBIN COMPLEX CONCENTRATES
D.3.9.1	CAS number	37224-63-8
D.3.9.3	Other descriptive name	PROTHROMBIN COMPLEX CONCENTRATES
D.3.9.4	EV Substance Code	SUB33011
D.3.10	Strength
D.3.10.1	Concentration unit	IU international unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	500
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	- Prothromplex TOTAL (Takeda (Baxter AG)1221 Wien)
D.2.1.1.2	Name of the Marketing Authorisation holder	Baxter AG
D.2.1.2	Country which granted the Marketing Authorisation	Austria
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	Prothromplex TOTAL
D.3.4	Pharmaceutical form	Powder and solvent for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Infusion (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PROTHROMBIN COMPLEX CONCENTRATES
D.3.9.1	CAS number	37224-63-8
D.3.9.3	Other descriptive name	PROTHROMBIN COMPLEX CONCENTRATES
D.3.9.4	EV Substance Code	SUB33011
D.3.10	Strength
D.3.10.1	Concentration unit	IU international unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	600
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: 3
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	No
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	Platelet concentrate
D.3.2	Product code	not applicable
D.3.4	Pharmaceutical form	Infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Infusion (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PLATELET CONCENTRATE
D.3.9.3	Other descriptive name	PLATELET CONCENTRATE
D.3.9.4	EV Substance Code	SUB14918MIG
D.3.10	Strength
D.3.10.1	Concentration unit	Other
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	individually
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	No
D.3.11.8	Extractive medicinal product	Yes
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

Liver cirrhosis

Leberzirrhose

E.1.1.1

Medical condition in easily understood language

Liver cirrhosis

Leberzirrhose

E.1.1.2

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

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	10024667
E.1.2	Term	Liver cirrhosis
E.1.2	System Organ Class	10019805 - Hepatobiliary disorders

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 evaluate the influence of a restrictive use of coagulation products on bleeding complications after interventions of the liver in patients with liver cirrhosis.

Evaluierung des Einflusses einer restriktiven Gerinnungssubstitution auf Blutungskomplikationen nach interventionellen Eingriffen an der Leber bei Patienten mit Leberzirrhose

E.2.2

Secondary objectives of the trial

To evaluate:
- Use of coagulation and blood products in the first three days after the intervention
- Incidence of bleeding complications over a period of 28 days after the intervention
- Correlation of bleeding complications with van Willebrand factor-, ROTEM- and thrombin generation-analysis at the time of the intervention
- Incidence of transfusion related events and thromboembolic events over a period of 28 days after the intervention
- 28 day bleeding- or thrombosis associated mortality
- Overall mortality

Gruppenvergleiche von:
- Verbrauch von Gerinnungs- und Blutprodukten im Zeitraum vom Tag der Intervention bis Tag 3 nach der Intervention
- Auftreten von Blutungskomplikationen im Zeitraum von 28 Tagen nach der Intervention
- Korrelation der Inzidenz von Blutungskomplikationen mit vWF, ROTEM-Analysen, und Thrombingeneration zum Zeitpunkt der Intervention
- Auftreten von transfusionsbezogenen Komplikationen im Zeitraum von 28 Tagen nach der Intervention
- Auftreten thromboembolischer Ereignisse im Zeitraum von 28 Tagen nach der Intervention
- 28-Tages Blutungs-/ Thromboembolie-assoziierte Mortalität
- 28-Tages Gesamt-Mortalität

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- liver cirrhosis
- elective micro wave ablation, radio frequency ablation, biopsy/puncture of the liver (percutaneous or transjugular), percutaneous transhepatic cholangiodrainage, transjugular intrahepatic portosystemic shunt
- INR > 1,5 and/or PLT count < 50 G/L

- Leberzirrhose
- Geplante Mikrowellenablation (MWA), Radiofrequenzablation (RFA), Biopsie/Punktion der Leber (perkutan oder transjugulär), perkutane transhepatische Cholangiodrainage (PTCD), transjugulärer interhepatischer portsystemischer Shunt (TIPS)
- INR > 1,5 und/oder Thrombozyten < 50 G/L

E.4

Principal exclusion criteria

- age < 18 years
- patients unable to consent
- clinical signs or history of bleeding
- recent thromboembolic event
- chronic kidney disease stage G4 or G5 according to KDIGO
- pregnant or breast feeding women
- not paused anticoagulant medication (except acteylsalicylic acid)

- Alter < 18 Jahre
- Besachwaltete Patienten, fehlende Reversfähigkeit
- Positive klinische Blutungsanamnese
- Rezente Thrombose
- Chronische Niereninsuffizienz im Stadium G4 und G5 nach KDIGO
- Schwangere oder stillende Frauen
- nicht pausierte gerinnungshemmende Medikation (ausgenommen Acetylsalicylsäure)

E.5 End points

E.5.1

Primary end point(s)

incidence of bleeding complications

Inzidenz von Blutungskomplikationen

E.5.1.1

Timepoint(s) of evaluation of this end point

3 days after the intervention

3 Tage nach der Intervention

E.5.2

Secondary end point(s)

- Use of coagulation and blood products in the first three days after the intervention
- Incidence of bleeding complications over a period of 28 days after the intervention
- Correlation of bleeding complications with van Willebrand factor-, ROTEM- and thrombin generation-analysis at the time of the intervention
- Incidence of transfusion related events and thromboembolic events over a period of 28 days after the intervention
- 28 day bleeding- or thrombosis associated mortality
- Overall mortality

- Verbrauch von Gerinnungs- und Blutprodukten im Zeitraum vom Tag der Intervention bis Tag 3 nach der Intervention
- Auftreten von Blutungskomplikationen im Zeitraum von 28 Tagen nach der Intervention
- Korrelation der Inzidenz von Blutungskomplikationen mit vWF, ROTEM-Analysen, und Thrombingeneration zum Zeitpunkt der Intervention
- Auftreten von transfusionsbezogenen Komplikationen im Zeitraum von 28 Tagen nach der Intervention
- Auftreten thromboembolischer Ereignisse im Zeitraum von 28 Tagen nach der Intervention
- 28-Tages Blutungs-/ Thromboembolie-assoziierte Mortalität
- 28-Tages Gesamt-Mortalität

E.5.2.1

Timepoint(s) of evaluation of this end point

28 days after the intervention

28 Tage nach der Intervention

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

E.8.1.3

Single blind

Yes

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

Pilotstudy

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

restrictive vs. liberal use of coagulation products

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

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.1.3

Elderly (>=65 years)

Yes

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 2022-09-13.

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

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

keine

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

2022-11-04

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-05-17

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2025-01-13

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