ISRCTN - ISRCTN04929580: In vivo changes in haemostasis after intravenous administration of plasma-derived factor VII and recombinant factor VII(a)

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 type

University/education

Website

http://www.ru.nl/english/

Funders

Funder type