Clinical Trials Register

Summary
EudraCT Number:	2008-005653-37
Sponsor's Protocol Code Number:	ICH-VKA
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:	2013-03-21
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

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A. Protocol Information

A.1

Member State Concerned

Denmark - DHMA

A.2

EudraCT number

2008-005653-37

A.3

Full title of the trial

Multicenter, prospective randomized trial on the use of prothrombin complex and fresh frozen plasma in patients with intracerebral hemorrhage related to vitamin K antagonists (VKA)

Multicenter, prospektiv randomiseret sammenligning af prothrombin complex og frisk frossen plasma ved Vitamin-K antagonist relateret intracerebral hæmorragi.

A.3.1

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

Acute treatment of stroke in patients reciving anticoagulant treatment

Akut behandling af hjerneblødning ved blodfortyndende behandling

A.3.2

Name or abbreviated title of the trial where available

ICH-VKA

A.4.1

Sponsor's protocol code number

ICH-VKA

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	Universityhospital of Heidelberg
B.1.3.4	Country	Germany
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	Octapharma AG
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	University of Heidelberg
B.5.2	Functional name of contact point	Coordination Center for Clinical Tr
B.5.3	Address:
B.5.3.1	Street Address	Vossstrase/Gebäude 4410
B.5.3.2	Town/ city	Heidelberg
B.5.3.3	Post code	69115
B.5.3.4	Country	Germany
B.5.4	Telephone number	+49062215634513
B.5.5	Fax number	+49062215633508
B.5.6	E-mail	anja.freiberger@kks-hd.de

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	Octaplex
D.2.1.1.2	Name of the Marketing Authorisation holder	Octapharma AD, Sweden
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.3.4	Pharmaceutical form	Powder and solvent for suspension for injection
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	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	Fresh frozen plasma - no trade name
D.2.1.1.2	Name of the Marketing Authorisation holder	Different blood banks in Denmark
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	Fresh frozen plasma
D.3.4	Pharmaceutical form
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 plasma coagulation factors
D.3.9.2	Current sponsor code	Fresh frozen plasma
D.3.10	Strength
D.3.10.1	Concentration unit	Other
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20 ml/ kg
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.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

Intracerebral hemorrhage (ICH) in patients related to vitamin K antagonists

Multicenter, prospektiv randomiseret sammenligning af prothrombin complex og frisk frossen plasma ved Vitamin-K antagonist relateret intracerebral hæmorragi.

E.1.1.1

Medical condition in easily understood language

Acute treatment of stroke related to anticoagulant treatment.

Akut behandling af hjerneblødning ved blodfortyndende behandling.

E.1.1.2

Therapeutic area

Body processes [G] - Bones and nerves physological processes [G11]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10022754
E.1.2	Term	Intracerebral hemorrhage
E.1.2	System Organ Class	100000004852

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Efficacy of PCC compared to FPP in patients with ICH-VKA

Sammenligning af effekt af PCC og FFP hos patienter med VKA-ICH

E.2.2

Secondary objectives of the trial

Safety and efficacy of PCC compared to FPP in patients with ICH-VKA

Sikkerhed og effekt af PCC sammelignet med FFP hos patienter med VKA-ICH

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Spontaneous ICH (intraparenchymal), subdural hematoma (SDH) diagnosed by CT scanning ≤ 12 hours after onset of symptoms. In case of unknown time of symptom onset: time between last seen in healthy condition and first CCT ≤ 12 hours.
2. Therapy receiving vitamin K antagonists (VKA)
3. International Normalized Ratio (INR) ≥ 2
4. Male or female subjects, age ≥ 18 years

Spontan TCH, SDH diagnosticeret ved CT indenfor 12 timer efter symptomdebut, hvis ukendt defineret som sidst set rask indenfor 12 timer inden CTC
2. I behandling med VKA
3. INR >=2
4.mindst 18 år gammel

E.4

Principal exclusion criteria

1 Patients with secondary ICH related to infarction, hemophilia or other coagulopathy, tumor, hemorrhagic infarction, cerebrovenous thrombosis, aneurysm, arteriovenous malformations (AVM) or severe trauma
2. Deep Coma (GCS ≤ 5) at the time of admission or before intubation if intubated outside the hospital
3. Known thrombocytopenia (platelets <50,000/L), hemorrhagic diathesis (primary defects of coagulation, fibrinolysis, platelets)
4. Pregnancy and lactation
5. Acute myocardial ischemia, acute septicemia, acute crush injury, any history of acute hemorrhagic disseminated intravascular coagulation, acute thrombotic stroke
6. Acute or known congestive heart failure (NYHA III, IV)
7. Pulmonary edema
8. Known history of claudicatio intermittens
9. Known recent thrombotic event < 30 days
10. Known active malignant disease
11. Known alcohol or other drug abuse
12. Known previous disability (mRS > 2 before stroke occurred)
13. Known liver failure (child-pugh-score C)
14. History of hypersensitivity to the investigational products or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational product
15. Known allergy to heparin or history of heparin induced thrombocytopenia.
16. Previous participation in this trial
17. Participation in ANY clinical trial within 30 days of entry into the trial and during the trial
19. Concomitant use of antithrombotic (with PTT > 1.5 of normal PTT), thrombolytic treatment. – Use of aspirin, clopidogrel or dipyridamole or combinations thereof (e.g. Aggrenox®) is not an exclusion criterion. These drugs should be discontinued and not restarted earlier than 24 hours after normalization of INR if indicated.

Sekundær ICH (infarkt, hæmofili, tumor,sinusthrombose,aneurisme, AVM eller signifikant hovedtraume)
2.Dyb coma defineret som GCS<=5 ved indlæggelse elle før intubation præ-hospitalt
3. Kendt koagulationsforstyrrelse
graviditet eller laktation
4. akut myokardieinfarkt, sepsis, vævsknusning eller tidligere dessimineret intravskulær koagulation.
6. Kendt hjertesvigt (NYHA III,IV)
7. Lungeødem
8. kendt Claudicatio
9.Kendt thrombose < 30 dage
10. Kendt aktiv malign sygdom.
11. Kendt alkohol eller stofmisbrug.
12. Kendt eksisterende handikap (mRS >2)
13. Kendt leversvigt
14. Kendt overfølsomhed overfor Octaplex eller hepariner.
15. tidligere deltagelse i denne trial eller deltagelse i anden interventionel trial indenfor 30 dage
16. absolut indikation for fortsat brug af plade-hæmmer under studiebehandlingen.

Aku

E.5 End points

E.5.1

Primary end point(s)

Number of patients with INR ≤ 1.2 3 hours after start of drug infusion

Antal patienter med INR<= 1,2 3 timer efter start af studiemedicin.

E.5.1.1

Timepoint(s) of evaluation of this end point

3 hours after initiation of study drug

3 timer efter start af studie medicin

E.5.2

Secondary end point(s)

1. Time to normalisation of INR (measured 30 min and 3 hours after start of infusion, or at the end of infusion if FFP is terminated before 3 hours)
2. Hematomagrowth defined as change in hematoma volume within 24 hours.
3. Modified rankin Scale, at day 15 and 90.
4. National Institute of health Stroke Scale at 15 days.
5. Glasgow outcome scale at day 90.
6. Barthel Index at day 90.
EQ-5D self-report questionnaire (Quality of life at day 90.

1. Tid til normalisering af INR (målt efter 30 min og 3 timer efter start af infusion, hvis FFP ved afslutning af infusion, hvis før 3 timer)
2. Hæmatomvækst defineret ved forskel i hæmatom volumen indenfor 24 timer.
3. Modified rankin Scale, pådag 15 og 90.
4. National Institute of health Stroke Scale på dag 15.
5. Glasgow outcome scale på dag 90.
6. Barthel Index på dag 90.
EQ-5D self-report questionnaire (Livskvalitet) på dag 90.

E.5.2.1

Timepoint(s) of evaluation of this end point

The above mentioned end points are evaluated at 15 days or 90 days as described under the individual items above

Evalueres efter 15 dage eller 90 dage som anført under de enkelte punkter

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)

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

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

blindet observatør

observer-blinded

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

Information not present in EudraCT

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

The trial ends after 74 subjects have been included and the last patient has finished the last visit.

Studieafslutningen er defineret ved at den sidste af de planlagte 74 forsøgspersoner er inkluderet og har gennemført det sidste besøg.

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

Information not present in EudraCT

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

Information not present in EudraCT

F.1.1.3

Newborns (0-27 days)

Information not present in EudraCT

F.1.1.4

Infants and toddlers (28 days-23 months)

Information not present in EudraCT

F.1.1.5

Children (2-11years)

Information not present in EudraCT

F.1.1.6

Adolescents (12-17 years)

Information not present in EudraCT

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

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

It is expected that the vast majority of patients with intracerebral hemorrhage are unconcious or of restricted conciousness and not able to give consent at their own at the time of admission to the hospital.

Det forventes at langt hovedparten af patienter med intracerebral hæmorragi er bevidsthedspåvirkede ved ankomsten til hospitalet og ikke kan afgive informeret samtykke. Der ansøges den Centrale Videnskabsetiske Komite om tilladelse til auktforsøg

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

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)

Patient care after the end of the trial will not differ from standard care applied in patients who are not included in this trial.

Ud over den akutte behandling vil alle patienter modtage vanlig behandling.

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

2013-03-21

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-03-22

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2015-02-06

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