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), w.vanheerde@labgk.umcn.nl
Dr Pal Andre Holme (Oslo, Norway)
Prof. Dr. Flora Peyvandi (Milan, Italy)
Trial website
Contact information
Type
Scientific
Primary contact
Dr Waander van Heerde
ORCID ID
Contact details
Radboud University Nijmegen Medical Center
LH 441
POBox 9101
Nijmegen
6500 GA
Netherlands
-
w.vanheerde@labgk.umcn.nl
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
PSTOL20
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
Acronym
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
Interventional
Secondary study design
Randomised cross over trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Factor VII deficiency
Intervention
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
Biological/Vaccine
Phase
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
07/05/2007
Overall trial end date
11/12/2008
Reason abandoned (if study stopped)
Eligibility
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
Patient
Age group
Adult
Gender
Both
Target number of participants
10
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 (SSRIs)
9.6. Hb levels < 7.5 mmol/l for women, < 8.4 mmol/l for men
Recruitment start date
07/05/2007
Recruitment end date
11/12/2008
Locations
Countries of recruitment
Italy, Netherlands, Norway
Trial participating centre
Radboud University Nijmegen Medical Center
Nijmegen
6500 GA
Netherlands
Sponsor information
Organisation
Radboud University Nijmegen Medical Center (Netherlands)
Sponsor details
Department of Laboratory Medicine
LH 441
POBox 9101
Nijmegen
6500 GA
Netherlands
+31 (0)24 361 0800
w.vanheerde@labgk.umcn.nl
Sponsor type
University/education
Website
Funders
Funder type
University/education
Funder name
Radboud University Nijmegen Medical Center (Netherlands)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
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: http://www.ncbi.nlm.nih.gov/pubmed/23834817
Publication citations
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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.