Background of the study
Coumarin derivatives (warfarin, phenprocoumon or
acenocoumarol) are oral anticoagulation drugs (a drug that "thins"
the blood). These drugs are used to treat patients with blood
clots in the veins and to prevent blood clots in people with
atrial fibrillation (rapid and irregular pulse rate) and other
heart problems.
If the blood is too "thin" or too "thick", it may cause adverse
drug reactions. The amount of coumarin derivative someone may
need to achieve the right "thickness of the blood" varies among
patients. That is why your degree of anticoagulation, expressed
in INR (International Normalised Ratio) has to be determined
frequently. The variation is mainly caused by differences in
genetic profile between people, but also by age, sex, diet and
comedication you might probably use.
The aim of this study is to investigate whether pre-treatment
determination of your genetic profile (in this case: unique
hereditary characteristics that influence the anticoagulation)
improves your anticoagulation therapy.
In total, almost 3000 coumarin derivative users divided over 3
oral anticoagulation drugs (acenocoumarol, phenprocoumon and
warfarin) from 7 European countries will participate in the
study.
Why you have been invited
You are invited to participate in the trial, since you will
start therapy with one of the coumarin derivatives (warfarin,
phenprocoumon or acenocoumarol) in the near future.
Design of the study
This study will compare two different ways of dosing, dosing
based on your genotype (your genetic information), clinical
information and if possible previous INR in the intervention
group (the group where knowledge of the genetic profile will be
taken into account in the treatment) and dosing based on
clinical information and if possible previous INR, in the
control group. If you decide to participate in the trial, you
will be randomised to either the intervention or the control
group. The possibilities to be randomized in one or the other
group are equal. You will not know in which group you are and
switching is not possible.
If you are participating in the trial, you will be dosed
according to one of the dosing formulas for 3 months. During the
study various information will be collected. Therefore
questionnaires, your medical information and blood samples will
be used to obtain this information.
What the study will mean to you
This investigation takes 3 months. At study start, some extra
blood samples will be taken to determine your genotype and INR
and for storage in Bioabanks. The samples in the Biobanks may be
used for further genetic analysis. You will be asked to complete
some forms, so we have information about your age, gender,
height, etc and your medication. We also ask you to give
permission to researchers to access your medical records, so
that information necessary for this trial can be collected. Your
INR will be determine, as with regular anticoagulation treatment.
This will be done on some scheduled visits. It is important that
you are attending these visits. Preceding a number of visits,
you will be asked to complete one or more questionnaires, which
will take you approximately 15 minutes per visit. At the last
visit again some extra blood samples will be taken.
After completion of the study, your data will be processed
anonymously. Since this is an international study, your
anonymous data will be transferred to the principal
investigators in other countries for further analysis during and
after the trial.
Load of the study
If you participate, 8 visits are already scheduled for you (which
may vary not more than 3 days). The number of visits during this
trial will not differ from the average number of visits you
would have if you would not like to participate in the trial.
By participation, you will be asked to complete 14
questionnaires (7 different ones), spread over 8 visits. Also,
during the first visit (just before you start taking the
coumarin derivative), some blood samples will be taken for
analyses. During the last visit again some extra blood samples
will be taken.
Risks of the study
The most important difference between the treatments you will
receive if you participate in the study and if you do not
participate in the study, is the way the dose will be determined.
If you do not participate in the study, dosage will be
determined by a physician. The physician uses information about
your previous INR, your previous dosages and experience to
determine your next dosing schedule. If you do participate in
the study, your dosing schedule will be calculated based on
information such as age, sex, height and weight, and if you are
randomised to the intervention group, also genetic information.
These formulas have not been used in the clinic before. Since
your INR will be checked frequently, which will also occur if
you decide not to participate in the trial, we do not expect an
increased risk of bleedings (due to high dosing) or thrombotic
events (due to low dosing) if compared to standard clinical
care.
Probable advantages of the study
It is difficult to determine whether you will have a personal
advantage by participation in the trial. It is expected that for
both groups in this study the INR will be kept between the
narrow therapeutic ranges better. Since this way of dosing is
not used in human before, it is not possible to say with
certainty that this is indeed the case. The obtained results
will be of value for future users of a coumarin derivatives.
Information that becomes available in the meantime
The study will proceed as accurate as possible according to the
protocol, but meanwhile the situation can change. For example
caused by a response of your body or if new information becomes
available. In that case, it will be discussed with you
immediately. You will decide whether the study may continue or
stop. In case your safety or wellbeing is at danger, we will
stop the study immediately.
After the study
The study takes 3 months. If you need treatment with your
coumarin derivative more than 3 months, than the treatment will
be continued after the study according to standard local
clinical care.
Participation in the study
Your participation is totally voluntary. If you give permission
to participate in the study, you are still free to withdraw from
the study at any time without giving a reason. Participation or
no participation will not affect the treatment you receive or
the relation with the employees of the centre where you are
being treated.
Confidentially of the data
It is ensured that all data will be treated confidentially. Data
will be treated according to the EU Data Protection Directive
(95/46/EU) and other country specific rules. Unauthorized people
do not have access to the data. Results of the study will be
used in scientific publications, but will not be convertible to
you as a person. If your data will be transferred to other
counties, your identity will be kept secret.
Information of your General Practitioner
We will inform your General Practitioner in writing if you
decide to participate in the study. This is for your own safety.
You need to give permission to inform your General Practitioner
on the Consent Form. If you do not give permission, you are not
allowed to take part in the trial.
Insurance
Insurance has been arranged for all participants. The insurance
covers all injure caused by this study.
Independent Ethics Committee
The Independent Ethics Committee in your country has reviewed
this study.
At last
If you decide to participate in the trial, you will be asked to
fill in your name and the date of signing and to sign the
Consent Form in duplicate. Signing the Consent Form does not
obligate you anything, but indicates that you have received this
information and understand what is asked from you regarding this
study.
Kindest regards,
The EU-PACT team |
