Participant Information Leaflet
ALIFE2 Trial
Low-molecular-weight heparin to increase the chance of live birth in women
with recurrent miscarriage and inherited thrombophilia.
Introduction
You are invited to take part in a research trial. Before you decide, it is important that you
understand why the research is being done and what it would involve for you.
Please take the time to read the following information carefully and take time to decide
whether or not you wish to take part. You are welcome to ask us if there is anything that is
not clear or if you would like more information. You might also want to talk to others about
the study (for example your family, friends or your GP).
In the rest of this leaflet Part 1 tells you the purpose of the trial and what will happen to you
if you take part. Part 2 gives you more detailed information about the conduct of the trial).
PART 1
What is the trial about?
It is well known that some women whose blood tends to clot more than normal have an
increased risk of miscarriage. That clotting tendency is called thrombophilia (sometimes also
described as “sticky blood”).
If this tendency has developed over time, perhaps as part of another illness, it is called
“acquired thrombophilia” and treatment with anti-coagulant or “blood-thinning” medication
has been shown to reduce the risk of miscarriage.
The situation is different for women who have inherited thrombophilia (i.e. passed down
from a parent). Although a large number of studies has shown that they also have a higher
than normal risk of miscarriage, it is not clear if anticoagulant medication will reduce that
risk or not.
This trial aims to try and find out if anticoagulant (“blood thinning”) treatment reduces the
risk of miscarriage in pregnant women who have inherited thrombophilia and who have had
at least two consecutive or non-consecutive miscarriages.
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The anticoagulant medication used in the ALIFE2 trial is called “low-molecular-weight
heparin” (LMWH).
LMWH is not currently standard care in pregnant women who have inherited thrombophilia,
because there is no evidence that it will benefit them. Some doctors do prescribe it for
women with this condition, however, this is based on the evidence that LMWH can reduce
the chance of miscarriage in pregnant women with the acquired form of thrombophilia.
We now understand that the potential causes of miscarriage in women with acquired
thrombophilia is different from the potential causes of miscarriage in women with inherited
thrombophilia. Therefore it is important to try and find out if LMWH actually does reduce
the risk of miscarriage in pregnant women who have inherited thrombophilia. That will
enable all doctors to make a decision based on clinical trial evidence when treating pregnant
women with inherited thrombophilia.
Can I take part in the trial?
You would be eligible to participate in the trial if you have inherited thrombophilia, have
experienced two or more miscarriages and you are less than 7 weeks pregnant. You would
not be eligible to participate in the trial if you are less than 50kg in weight or you are
prescribed LMWH during pregnancy for other reasons, such as deep vein thrombosis,
mechanical heart valves or if your kidney function is impaired.
Do I have to take part?
It is entirely up to you to decide. We will describe the study and go through this information
sheet, which we will give you to keep. If you choose to participate, we will ask you to sign a
consent form to confirm that you have agreed to take part. Your signature is not binding in
any way and you will be free to withdraw at any time, without giving a reason. This will not
affect you or your care in any way.
If your doctor believes that is in your best interest for you to stop participating in the trial, he
or she will discuss this with you.
If any new information regarding your treatment becomes available during the course of the
trial, your doctor will discuss this with you as well.
Whether you decide to participate in the trial or not, your decision will not affect your
relationship with your doctor.
If you decide not to participate in the trial, you will receive the usual standard of care for
your pregnancy.
What will happen to me if I take part?
If you are eligible for the trial and you wish to take part you will first be registered onto the
trial. This means you will be asked to provide written informed consent to confirm you wish
participate in the trial. The hospital trial team will then contact the Warwick Clinical Trial
Unit to register you on the trial.
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As soon as you have a positive pregnancy test you would then contact your research team to
arrange a hospital visit and you would be “randomised” onto the trial to allocate which
treatment you will receive. A computer will randomly assign participants to receive either
standard care with LMWH or standard care without this medication. It is only by this
random assignment (like tossing a coin) that we can find out if fewer miscarriages occur to
women who receive the anticoagulant medication, LMWH, compared with those who don’t.
In order to make this trial valid, neither you nor your physician can have any influence on
which group you are assigned to.
If you are assigned to the 'LMWH group', you will start the medication once you are
pregnant (confirmed by a positive urine pregnancy test), and will continue until the first
signs of labour. The treatment involves injecting yourself with a small needle into the skin of
your abdomen or thigh once daily.
You will be provided with medication to take home with you. You will be supplied with
enough medication to last between your normal hospital visits. The medication will be in the
form of pre-filled syringes so that it is already prepared for you to use by yourself. You will
also be provided with a diary to record when you have injected the medication each day and
be provided with a container for safe disposal of injection needles. You will be asked to
return the container (and contents) to the hospital trial staff at each standard hospital visit.
You will receive training from the hospital trial team on how to inject the medication and
they will observe and guide you the first time you do this yourself. You will be able to receive
refresher training if you wish.
At three time points during the trial, a blood sample (2.7 milliliters or ½ teaspoon) will be
taken to assess your platelet count (platelets are part of the body’s clotting mechanism). The
first blood sample is taken to ensure you are eligible for the trial, the second blood sample is
to assess your platelet count before you start trial medication and the third is to check your
platelet count after you have been on the trial medication for one week (more detail on this
is provided in the next section). You would normally have two blood samples taken during
routine care, so only the third blood sample is extra as a result of being in the trial and you
may be able to have this taken at your GP surgery.
If you are assigned to the group that does not receive the LMWH, you will receive the usual
standard of care for your pregnancy, except that your data will be collected for the purposes
of the trial.
For both groups, details of your pregnancy will be recorded. For the purpose of the trial we
will ask for your permission to collect information about your obstetric and medical history
and the course of the current pregnancy. In addition we will collect results from blood tests
and ultrasound scans that are part of the standard of care of pregnancy. Data collected from
your pregnancy will be compared to the data from other women who participate in the
ALIFE2 trial, with the purpose of determining whether LMWH, reduces the risk of
miscarriage. The trial concludes 6 weeks after delivery or miscarriage. This will be your last
visit for the purposes of the trial. Your normal care will then continue as usual once your
have completed all trial visits.
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What are the possible disadvantages, side effects, risks and/or discomforts of taking part
in this study?
Treatment with LMWH as prescribed in the ALIFE2 trial is already standard practice for
women with deep vein thrombosis in pregnancy, where an even higher dose is used.
Treatment is therefore generally considered safe to be used in pregnancy.
However, there are potential side effects with the use of LMWH. Side effects may include
bruising (especially at the injection site), bleeding, allergic reactions, a low blood platelet
count and osteoporosis. These last two events are very rare, but as a precautionary
measure, a platelet count will be performed during the trial. LMWH does not cross the
placenta and is therefore not harmful to the baby. When you have your blood test for your
platelet count, you may experience some bruising around the area where the blood was
taken.
What are the possible benefits of taking part in this study?
We do not know whether taking part in the trial may be beneficial to you personally.
However we hope that the results of this trial may be beneficial to women with unexplained
recurrent miscarriage and inherited thrombophilia in the future. If treatment with LMWH
appears to be effective, it can reduce the number of miscarriages. If treatment with LMWH
is not effective, unnecessary treatment with LMWH can be avoided in the future.
Expenses and payments
No expenses or payments will be made for participation in this study.
If you are assigned to standard care without LMWH you will not be asked to visit the
hospital at any time other than when you normally would for your pregnancy care.
If you are assigned to standard care with LMWH the only additional visit will be for the third
blood sample to check your platelet count. However, it may be possible to provide this
sample at your GP surgery.
What will happen when the trial ends?
The trial concludes 6 weeks after delivery or miscarriage and, once you are discharged from
hospital care, your GP will continue with your care as normal.
When the last participant has completed the trial, the information we have gathered will be
analysed so that we can work out whether or not there is any benefit from the use of
LMWH.
What if there is a problem?
If you have a concern about any aspect of this study, you should ask to speak to your study
doctor or nurse who will do their best to answer your questions (see the end of this leaflet
for contact details). If you remain unhappy and wish to complain formally, you can do this
through the Patient Advice and Liaison Service (PALS). Their full contact details are given in
Part 2 of this leaflet.
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This concludes Part 1.
If the information in Part 1 has interested you and you are considering participation,
please read the additional information in Part 2 before making any decision.
__________________________________________________________________________
Part 2
Who is organising and funding the trial?
This trial is funded by the Research for Patient Benefit Programme which is within the
National Institute for Health Research (NIHR). The NIHR was set up in 2006 by the
government to provide organised funding for research within the NHS.
University Hospitals Coventry and Warwickshire NHS Trust is sponsoring the trial and
covering the standard insurance and indemnity costs applicable to research trials.
The University of Warwick Clinical Trials Unit is organising the administration of the trial.
Professor Siobhan Quenby is the Chief Investigator, who has overall responsibility for the
trial.
What will happen if I don’t want to carry on being part of the study?
Participation in this study is entirely voluntary. If you decide you do not wish to participate
in this trial it will not affect you in any way. If you decide to take part in the study, you will
need to sign a consent form, which states that you have agreed to participate. However,
you may withdraw from the study at any time without giving a reason and without it
affecting you in any way.
You have the right to withdraw from the study completely and decline any further contact by
study staff after you withdraw.
Your normal care will not be affected in any way.
Who should I contact if I wish to make a complaint?
If you have a concern or complaint about the Trial which has not been addressed by the
study team, you can complain formally through the Patient Advice and Liaison Service
(PALS):
Patient Advice and Liaison Service
John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust
Headley Way, Oxford, OX3 9DU
Email: palsjr@ouh.nhs.uk (Start your subject line with FAO: PALS)
Tel: 01865 221473 (9:00am – 5:00pm Monday to Friday, 24 hours answerphone)
Will my taking part be kept confidential?
Once you have agreed to participate, information about you is sent to the ALIFE2 Trial Office
which will refer to you only by a unique trial number, your initials, date of birth and hospital
number so that you cannot be recognised. All information collected about you for this trial
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is strictly confidential. The information will be securely stored at Warwick Clinical Trials Unit
under the provisions of the 1998 Data Protection Act, and will be accessible only to
authorised personnel from the ALIFE2 Trial Office.
Occasionally, we may need to access your medical records in order to check that the
information provided about you is accurate. This will be done by clinical staff or designated
personnel from the Trial Office.
Government regulatory agencies may also require access to your medical records to ensure
that the trial is being run in accordance with UK law.
We will inform your General Practitioner of your participation in the trial. If you do not wish
your GP to be informed then you would not be able to participate.
Only the local investigator at your hospital will have access to your personal details and can
trace your identity. Data collected for the trial will be stored for up to 10 years after the end
of the trial, as required by UK legislation.
What will happen to the results of the trial?
Once the study is complete the results will be published and a final report will be written.
The results will be available on the Warwick Clinical Trials Unit website and will be provided
to your local hospital participating in the ALIFE2 trial. Information relating to the study may
be communicated in scientific meetings. You will not be identified in any reports or
publications and none of the data could be traceable to you personally.
Who has reviewed and approved the trial?
This trial was reviewed and approved by the NRES Committee West Midlands – Coventry &
Warwickshire, the Medicines and Healthcare products Regulatory Agency (MHRA) who are
the UK government’s authority who oversee all clinical trial activities and also by the
Research and Development Office at your hospital.
What if I want any more information about the study?
If you have any questions about any aspect of the study, or your participation in it which has
not been answered by this participant information leaflet, then please contact:
Principal Investigator: Ingrid Granne - Telephone number: 01865 740887
Senior Research Fellow in reproductive Medicine
Nuffield Dept. Obstetrics and Gynaecology, University of Oxford
Research Midwives – Arancha de la Horra, Nicola Higgins and Sarah Harding - Telephone
number: 01865 572258
Thank you for taking the time to read this Participant Information Leaflet
This project was funded by the National Institute for Health Research, Research for Patient Benefit - RfPB
(project number PB-PG-101332011).
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