Condition category
Haematological Disorders
Date applied
Date assigned
Last edited
Retrospectively registered
Overall trial status
Recruitment status
No longer recruiting
Publication status

Plain English Summary

Background and study aims
Factor VII is a protein produced in the liver that plays an important role in helping the blood to clot. Factor VII deficiency is a rare inherited bleeding disorder due to a diminished level of factor VII in the blood. Factor VII deficiency cannot be cured but bleeding episodes can be treated with factor VII either taken from donated blood (plasma-derived) or produced artificially (recombinant). These products are not only used to treat bleeding episodes but also to prevent bleeding. However, it is not known why this preventive treatment is successful. The aim of this study is to unravel the mode of action of both products in these patients.

Who can participate?
Patients aged 18 or older with severe factor VII deficiency.

What does the study involve?
Patients are treated with both products in a time frame of at least six weeks. Half of the patients are treated with a single injection of recombinant factor VII followed after at least six weeks with an injection of plasma-derived factor VII. The other half of the patients are treated in the reverse order.

What are the possible benefits and risks of participating?
As both products are used for the treatment of bleeding episodes in these patients the risk of adverse events is limited.

Where is the study run from?
The study will be performed at two central locations at the clinical research centers of the Radboud University of Nijmegen and in Milano.

When is the study starting and how long is it expected to run for?
May 2007 to December 2008.

Who is funding the study?
The De Erven Leeuwenhart Foundation. The products will be supplied by Novo Nordisk (recombinant factor VII) and Baxter (plasma-derived factor VII).

Who is the main contact?
Dr Waander van Heerde (Nijmegen, The Netherlands),
Dr Pal Andre Holme (Oslo, Norway)
Prof. Dr. Flora Peyvandi (Milan, Italy)

Trial website

Contact information



Primary contact

Dr Waander van Heerde


Contact details

Radboud University Nijmegen Medical Center
LH 441
POBox 9101
6500 GA

Additional identifiers

EudraCT number number

Protocol/serial number


Study information

Scientific title

In vivo changes in haemostasis after intravenous administration of plasma-derived factor VII and recombinant factor VII(a): a randomised controlled cross over multicentre intervention study


Study hypothesis

The basis of suppletive therapy with plasma derived factor (pdF) VII or recombinant factor (rF)VIIa is not only restoration of the coagulation cascade but also presensitise platelets and effects the genetic regulation of other clotting factors

Ethics approval

Human Subjects Research Region Arnhem-Nijmegen (Commissie Mensgebonden Onderzoek Regio Arnhem-Nijmegen), 30/03/2004, CMO 2003/257

Study design

Randomised controlled cross over multicentre intervention study

Primary study design


Secondary study design

Randomised cross over trial

Trial setting


Trial type


Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet


Factor VII deficiency


1. Ten severe factor VII patients will be treated with two factor VII containing products in a time frame of at least six weeks
2. Five patients will be treated with a single intravenous injection of recombinant activated factor VII (20 ug/kg, Novo Nordisk) followed after at least six weeks with a intravenous injection of plasma derived factor VII (25 IU/kg, Baxter)
3. The other five patients will be treated in the revise order
4. Within 48 hours blood samples will be drawn to analyse different haemostatic parameters in their blood

Intervention type



Drug names

Primary outcome measure

Pharmacokinetic and pharmacodynamic analysis of recombinant activated factor VII and plasma-derived factor VII

Secondary outcome measures

No secondary outcome measures

Overall trial start date


Overall trial end date


Reason abandoned (if study stopped)


Participant inclusion criteria

1. Factor VII clotting activity of less than 5%
2. Age 18 years or older
3. Wash-out period of pdFVII or rFVII(a) of at least 3 days
4. Male or female
5. The intention to participate in a cross-over design (treated-twice)

Participant type


Age group




Target number of participants


Participant exclusion criteria

1. Age < 18 years
2. Known allergy to plasma proteins
3. Bleeding episode resulting in a drop in haemoglobin (Hb) levels of >1 mmol/l (64.5 g/l), trauma or surgery in the last 6 weeks
4. Fever (> 38 degrees centigrade)
5. Clinical indication of liver cirrhosis (echographic indication, enlarged spleen, enlarged liver, decreased platelet count)
6. Hepatitis C recently treated with interferon (wash-out 6 months)
7. Human immunodeficiency virus (HIV) positive
8. Pregnancy
9. Medication:
9.1. Non-steroid anti-inflammatory drugs (NSAIDs)
9.2. Clopidogrel
9.3. Antimicrobial medication
9.4. Thyroid inhibitors
9.5. Serotonin-specific reuptake inhibitor (SSRI’s)
9.6. Hb levels < 7.5 mmol/l for women, < 8.4 mmol/l for men

Recruitment start date


Recruitment end date



Countries of recruitment

Italy, Netherlands, Norway

Trial participating centre

Radboud University Nijmegen Medical Center
6500 GA

Sponsor information


Radboud University Nijmegen Medical Center (Netherlands)

Sponsor details

Department of Laboratory Medicine
LH 441
POBox 9101
6500 GA
+31 (0)24 361 0800

Sponsor type




Funder type


Funder name

Radboud University Nijmegen Medical Center (Netherlands)

Alternative name(s)

Funding Body Type

Funding Body Subtype


Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Basic results (scientific)

Publication list

2013 results in:

Publication citations

  1. Results

    Mathijssen NC, Masereeuw R, Holme PA, van Kraaij MG, Laros-van Gorkom BA, Peyvandi F, van Heerde WL, Increased volume of distribution for recombinant activated factor VII and longer plasma-derived factor VII half-life may explain their long lasting prophylactic effect., Thromb. Res., 2013, 132, 2, 256-262, doi: 10.1016/j.thromres.2013.05.027.

Additional files

Editorial Notes