TO BE PRINTED ON LOCAL TRUST HEADED PAPER
Version 1.2, 16th January 2015
SPIRO- CKD Trial
PARTICIPANT INFORMATION SHEET
We would like to invite you to take part in a research study. Before you decide, we would like
you to understand why the research is being done and what it would involve for you. Please
take time to read the following information carefully. Talk to others about the study if you wish.
Ask us if there is anything that is not clear or if you would like more information. Take time to
decide whether or not you wish to take part.
Part 1
What is the purpose of the study?
About 1 in 10 people in the UK have mild chronic kidney disease (CKD). Patients with kidney
disease are at increased risk of hardening of the blood vessels, which can lead to heart disease
and strokes. We are investigating a medication called spironolactone which has been used to
treat patients with high blood pressure, heart disease or liver disease for a long time. In a
smaller trial of patients with mild kidney disease, spironolactone seems to improve heart function
and reduces hardening of the blood vessels. We also noted that spironolactone reduced blood
pressure. We want to find out if spironolactone acts in a unique way to improve heart function
and blood vessel function or whether these effects are simply due to the lower blood pressure.
To do this we are running a new trial which will treat half of the patients with spironolactone and
half with another blood pressure lowering medication called chlortalidone. Chlortalidone is a
standard drug to treat blood pressure but works in a different way to spironolactone.
Do I have to take part?
No you do not. It is up to you to decide if you wish to join the study. If you agree to take part,
we will then ask you to sign a consent form. You are free to withdraw at any time, without giving
a reason. Your medical care will be unaffected whether or not you take part.
Why have I been invited?
You have been invited to take part in this research study because you have been found to have
evidence of mildly reduced kidney function according to the records available to us.
Who else is taking part?
We are inviting people like you, from different hospitals around the UK to take part. We need a
total of 350 patients with early kidney disease to participate in this research study.
What will happen to me if I take part?
Participation in this study is voluntary. If you decide that you would like to take part in this
study, a member of the study team, usually a research nurse, will explain the study to you and
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answer any questions you might have. They will ask you some questions about your health and
any medication you may be taking. You will then be asked to sign a consent form. You should
only do this if you are happy that you understand the project and want to take part.
Once you have agreed to take part and signed the consent form, we will arrange the first
investigations. Your initial study visit will involve the following tests:
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Measurement of height, weight and blood pressure
Blood sampling. A routine blood test from a vein in your arm. We would require
approximately 50ml (10 teaspoons) of blood
Urine sampling. We would require approximately 20 ml of urine (4 teaspoons)
Artery stiffness measurement. This simple test involves placing a pen-like probe onto the
pulse in the wrist, neck and groin to determine the stiffness and pattern of blood flow in
your arteries. No needles are involved and it is painless. This test takes 20-30 min
Cardiac MRI (magnetic resonance imaging). This scan creates detailed pictures of your
heart and arteries. It involves lying on a bed in an open-ended tunnel scanner. The scan
uses no X-rays or radiation and is painless and risk free. The duration of the standard
MRI scan for the main trial will be 30 minutes. If you consent to sub-study A it will take
an extra 5 minutes for some more images to be taken asking you to hold your breath
intermittently. These extra images will allow us to examine the function of your heart in
detail to see if the medications exert effects on the contraction or relaxation functions of
your heart. Please read the separate ‘Sub-Studies Information Sheet’ for more details
If you are prepared to do a more detailed cardiac MRI study, sub-study B, you will have a
small plastic tube called a cannula inserted into a vein in the arm. This is used to
administer a low dose of contrast called gadolinium which allows us to see any heart
damage. The gadolinium is safe and is routinely used in patients with mild stable kidney
disease and heart disease. There are no special precautions needed either before or
after the injection. The total scan time for sub-study B will be an extra 30 minutes taking
approximately 60 minutes in all. These extra images will allow us to examine the heart
walls to see whether the medications prevent fibrous tissue accumulating within the
walls. Please read the separate ‘Sub-Studies Information Sheet’ for more details
A 24 hour ambulatory blood pressure monitor. You will wear a portable monitor which will
be programmed to automatically record your blood pressure over a 24 hour period during
a normal day at home or work
A computer will then decide at random (like tossing a coin) which type of treatment you will have.
Half of the people taking part will be prescribed spironolactone and the other half will be
prescribed chlortalidone. This medication needs to be taken once a day, every day during the
study (40 weeks) in addition to your usual medications. It is very important that the treatments
cause an equal fall in blood pressure with both medications. We will measure your blood
pressure regularly and adjust the medication in each treatment group if necessary using extra
but standard blood pressure tablets.
Over the course of the study, you will be followed-up with study visits to the hospital to check
your blood ‘potassium’ level at weeks 2, 4, 8, 24, 40 and 46. At 40 weeks, we will repeat all the
measurements performed at your first visit. You will then stop the trial medication. At the end
of the study (week 46 which is 6 weeks after the trial medication is stopped), we will ask you to
attend a final clinic to have a repeat blood and urine test, as well as repeat measurement of your
artery stiffness. A summary of the trial procedures is shown in the flowchart below.
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Flowchart of trial participation:
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What will I have to do?
You will need to take the study medicine regularly during the course of the study (40 weeks) and
attend all the study visits. We will ask you to report any missed tablets during the study period.
You should also continue taking all of your normal tablets. We will review your medication
before you start the study to make sure the study medication does not interfere with your usual
tablets.
We will ask you to tell us if your GP starts you on any new medicines during the study. If your
‘potassium’ level is found to be high or low on the blood test during the study period, we might
change the dose of your medication and ask you to restrict or increase certain foods using
information given in an information sheet.
What happens at the end of the research study?
After the last clinic visit (6 weeks after you finish the study medication) the results will be studied
and analysed. Your usual medical care will continue as before once the study is completed. You
will not re-start the study medication. All specimens collected during the study will be stored for
at least 5 years after the completion of this study. If you would like to know the results we will
send you a summary.
Will I get paid for taking part?
We are unable to pay you for participating but we will reimburse your travel expenses to and
from the hospital for all visits.
What alternative treatments are available?
There are currently no other medicines licensed for reducing stiffness of the blood vessels in
patients with early kidney disease.
What are the possible risks of taking part?
With the exception of the blood tests, study procedures should not cause any pain or discomfort.
A small number of patients find the MRI scanner claustrophobic. If this were to occur, you would
be removed from the scanner immediately.
There are small risks with spironolactone. These include: increased levels of potassium salt in
the blood, reduced kidney function or low blood pressure. If any of these occur we would reduce
the dose of this medication (change to alternate days) or stop it completely. However, the dose
of the trial medication is relatively low and you will be closely monitored during the study to
ensure that those risks are minimised.
Spironolactone should be avoided during pregnancy. If you are a woman of child-bearing age,
we would ask you for permission to perform a pregnancy test prior to starting the trial medication
and to agree not to become pregnant whilst taking it. If you do become pregnant during the
course of the study, you must stop taking trial medication immediately and inform our research
team so an appropriate course of action can be taken.
What are the other side effects of the treatment received when taking part?
Spironolactone and chlortalidone are generally well tolerated drugs without many side effects. In
rare cases (less than 1 in 100) side effects of spironolactone can be allergic reactions (usually
rash, hives or itching), change in bowel habit, dark urine, and in women irregular or missed
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menstrual periods. In men spironolactone can occasionally (about 1 in 20 men) cause slight
tender enlargement of the breast tissue. If this happens we would like you to continue to take
part in the study as we know this problem will always fully resolve when you stop the drug. You
can of course withdraw from the study if you feel this side effect is not tolerable.
Chlortalidone is usually well tolerated but occasionally can cause rashes, stomach upset, upset
salts in the blood (low sodium or potassium), an increase in blood sugar and gout.
What are the benefits of taking part?
Our previous research study showed that spironolactone improves heart function and reduces
hardening of the blood vessels in patients with mild kidney disease in our specialist hospital
kidney clinic. However, we are unable to guarantee any direct benefit to you as a result of taking
part in this study. Nonetheless, you will contribute to an improved understanding of
spironolactone and its effects on blood vessel and kidney disease. The information gained from
this study will also contribute to further studies and may help improve the treatment of people
with kidney disease in the future.
What if there is a problem?
Any complaint about the way you have been dealt with during the study or any possible harm
you might suffer will be addressed. The detailed information on this is given in Part 2 (contained
in this leaflet).
Will my taking part in the study be kept confidential?
Yes. We will follow ethical and legal practice and all information about you will be handled in
confidence. The details are included in Part 2.
What will happen if I don’t take part?
Participation is entirely voluntary. If you decide not to take part then you will continue to be seen
as before in outpatient clinics. A decision not to take part will not affect your routine care in any
way.
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.
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Part 2
What if relevant new information becomes available?
Sometimes we get new information about the treatment being studied. We will tell you and your
doctor about it and give you an opportunity to discuss it with a trial nurse or doctor. If this new
information means that we should stop the study, or change how we are running it, we will do
this and make sure that you are offered the best treatment.
What will happen if I do not want to carry on with the study?
You are free to withdraw from the study at any time and this will not affect your care. You can
either withdraw completely or choose to keep in contact with us to let us know your progress.
Information collected earlier in the study may still be used.
What if there is a problem?
If you have concerns about any aspect of this study, you should ask to speak to the research
coordinator who will do her best to answer your questions (contact numbers below).
We do not anticipate that anything will go wrong. We will of course take great care that nothing
goes wrong but if you are harmed by taking part in this research you should understand that
there are no special compensation arrangements. If you are harmed due to someone’s
negligence, then you may have grounds for a legal action but you may have to pay for it.
Regardless of this, if you wish to complain, or have any concerns about any aspect of the way
you have been approached or treated during the course of this study, the normal National Health
Service complaints mechanisms are available to you: ask to speak to the complaints manager of
the hospital.
If you have a concern about any aspect of this study you should ask to speak to the researcher
who will do their best to answer your questions (insert Local PI contact details here). If you
remain unhappy and wish to complain formally you can contact your local Patient Advice and
Liaison Services (PALS) group or local equivalent group (insert name where applicable) (insert
contact details here).
Will my taking part in the study be confidential?
Yes. We will follow ethical and legal practice and all information about you will be handled in
confidence. If you agree to take part, your doctor will send basic information about you and your
condition to the SPIRO-CKD Trial Office at the University of Birmingham Clinical Trials Unit
(BCTU), on paper and electronically, where it will be securely stored under the provisions of the
Data Protection Act 1998 and/or applicable laws and regulations. Information held by the NHS
may be used to follow your progress. The study data may also be looked at by representatives
of regulatory authorities and by other authorised people to check that the study is being carried
out correctly. Your GP, and other doctors involved in your clinical care, will be kept informed. All
those associated with the study will have a duty of confidentiality to you as a research
participant.
In line with Good Clinical Practice Regulations, at the end of the study, the data will need to be
securely archived for at least 5 years (but ideally not less than 25 years). Arrangements for
confidential destruction will then be made.
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Will my GP be told that I am in a study?
Yes, we will inform your GP of your involvement in the study.
What will happen to any samples I give?
During study visits, blood and urine samples will be taken from you. These will be labelled with
your trial number. These samples will be anonymised (labelled without your name) and initially
kept in a freezer in a secure room in the hospital dedicated for this trial. Samples may then be
sent to other storage centres and eventually the samples will be analysed to measure a variety
of markers of health status. The research laboratories doing this analysis are situated in the UK
and also overseas, within Europe. In some cases samples will be stored and analysed by a
pharmaceutical company (Astra Zeneca – a UK/ Swedish company have agreed to store and
analyse many of our samples). At the end of the study, some extra samples will be kept for 10
years and might be used for other future ethically approved studies.
Will any genetic tests be done?
No genetic tests will be performed routinely. If you give permission, we will extract DNA from
cells in your blood sample and analyse your genes to look for genetic factors that might
contribute to heart and blood vessel disease in kidney disease or to your response to drug
treatment. This is a separate part of the study and we will ask you if you want to take part in this.
What will happen to the results of the research study?
The results of the research will be published in international, peer-reviewed scientific journals.
The results will also be available on the website www.clinicaltrials.gov. No personal information
will be identifiable in any report or publication.
Who is organising and funding the research?
The study is being coordinated by the University of Birmingham Clinical Trials Unit and is funded
by the British Heart Foundation. The research doctors will not receive a payment for including
you in this study.
Who has reviewed the study?
This study has been reviewed and approved by the <insert name > Research Ethics Committee.
What if I have more questions or do not understand something?
We will be pleased to answer any questions you may have or clarify things you do not
understand. You can contact the SPIRO-CKD team on <insert contact details>.
If you wish to discuss the study with a doctor who is not directly involved with the study you may
contact Dr <insert name and contact details>.
Thank you for taking the time to read this Participant Information Sheet
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