<To be printed on hospital headed paper> Patient Information Leaflet: Part 1 select-d Anticoagulation Therapy in SELECTeD Cancer Patients at Risk of Recurrence of Venous Thromboembolism Introduction This information sheet describes a research study that is taking place at the University of Warwick. Your health care provider is involved with recruiting participants for the study, and giving and monitoring care. The study is called select-d and is comparing two different types of treatment for a blood clot in people who have or have had cancer, and also looks into the ideal length of time to give the treatment for. Invitation It has been confirmed that you have a blood clot (sometimes called a thrombosis). These blood clots are more common in people who have had or are having treatment for cancer. We would therefore like to invite you to take part in this research study. Before you decide whether or not you are willing to participate, we would like to explain why the research is being done and what it will involve. Please take time to read the following information carefully and please feel free to discuss it with friends, relatives and your health care providers. Part 1 (this part) explains the purpose of this study and what will happen to you if you decide to take part. Part 2 provides you with more detailed information about the way the study will be carried out. select-d PIL v2.0; 05-Apr-2013 1
A member of your hospital or community care team will go through this information leaflet with you. Please ask us if there is anything that is not clear or if you would like more information. Please take time to decide whether or not you wish to take part. Please be assured that taking part in this research is entirely voluntary. If you decide not to take part, your medical care will not be affected in any way. What is the purpose of the study? Thrombosis or blood clots are a major problem facing people with cancer. It appears that cancer cells can release chemicals which make the blood thicker than usual and therefore more likely to form a clot. A thrombosis may cause a red, painful, swollen leg or arm (a deep vein thrombosis or DVT) or, if bits of the clot break off and are carried to the lungs, sudden onset of breathlessness, cough or chest pain (a pulmonary embolus or PE). The clots require treatment as some may be life-threatening. Advances have been made in developing new blood thinning treatments to treat blood clots, called anticoagulants. Standard treatment is with a daily injection under the skin of a blood thinning agent called dalteparin or Fragmin which has been shown to have advantages over warfarin in patients with cancer who were treated for 6 months. Dalteparin helps to dissolve the clot and prevent others forming. A new blood thinning agent called rivaroxaban or Xarelto has been used as an alternative to dalteparin in some research studies. Rivaroxaban has the advantage of being a tablet rather than an injection. Whether to stop or continue anticoagulation after 6 months, however, remains uncertain with no previous research studies having assessed this question in cancer patients to date. More research is needed on the effectiveness of rivaroxaban as it is not yet known whether dalteparin or rivaroxaban is better at treating and preventing clots in people with cancer or for how long the drugs should be taken (6 months or 12 months). The purpose of the study is to find out whether rivaroxaban is as good as dalteparin at treating clots and preventing other clots from forming, and whether it is better to give anticoagulant treatment for 6 or 12 months. select-d PIL v2.0; 05-Apr-2013 2
Why have I been invited? You have been invited to take part as you have cancer, or have had cancer in the past, and now have a blood clot. Do I have to take part? No. It is entirely up to you to decide whether or not to take part. If you do, you will be asked to sign a consent form. If you later change your mind about participating, you will be free to withdraw at any time and without giving a reason. If you decide not to take part, or if after joining the study you decide to withdraw, the standard of care you receive will not be affected. What will happen to me if I take part? All people who choose to take part in the study will be allocated their anticoagulant drug randomly (by chance) - we call this randomisation. The study will involve an initial 6 months treatment and then (for the majority of people but only if indicated) a further six months of treatment. Both treatments will be allocated by randomisation using a computer. You have an equal chance of receiving either treatment at each randomisation but you will not be able to choose. Your treatment will be randomly assigned to you by the Study Coordinating Centre at the University of Warwick. First Randomisation: The initial treatment will be: Group 1 Dalteparin injections given just under the skin (standard therapy in the UK). The injections will be given by yourself, a member of your family, a carer or a district nurse. or Group 2 Rivaroxaban tablets (research study therapy). Standard (non-trial) treatment would usually stop at six months after the onset of a blood clot. However, if you join the study, and have a DVT, you will have an ultrasound scan of the area around your DVT at about five months to see whether the blood clot has completely dispersed or if there is any of it left (known as residual vein thrombosis ). If the clot has select-d PIL v2.0; 05-Apr-2013 3
completely dispersed you will have no further treatment. However, if the scan indicates that the clot has not completely gone, or if you initially had a pulmonary embolism, you will be allocated by random, to a further six months of the tablet anticoagulant or a placebo (dummy) tablet. This is because we are hoping to find out whether the potential benefit of further anticoagulant treatment outweighs the potential side-effects. Longer treatments may have the benefit of giving more drug to the clot but they have the disadvantage of causing more treatment side effects. In this case, the most serious side effect is bleeding, which is discussed later in this leaflet. Second Randomisation: The second treatment will be: Group 1 Placebo (a dummy tablet that has no activity) or Group 2 Rivaroxaban (study tablets) Studies that have placebo treatments are necessary to produce the most reliable results about the treatment and whether longer or shorter anticoagulation therapy is more beneficial. It is important that neither you or your doctor or your research nurse knows which type of tablet you are taking so that information recorded within the trial is not influenced by this knowledge. However, this information can be found out by your doctor if there is an important clinical reason to do so. Information about your progress will be collected for two years. Part of the research is to compare whether either treatment has an impact on your quality of life (general wellbeing). To assess this, you will be asked to fill in questionnaires at certain intervals (before your treatment starts, every 3 months for the first year and then at 18 months and 24 months after the onset of the clot). We will also ask you to complete questionnaires about whether the disease and its treatment affect your finances. This is to monitor and identify any financial burden to participants and their families caused by either of the treatments given in this study. The research team will also record your progress in your hospital/gp notes during routine clinic visits. select-d PIL v2.0; 05-Apr-2013 4
At the start of the study, at 3 months, at 6 months and, if your treatment continues for a year, at 12 months, you will be also have an additional research blood sample taken from you. This will be used to add to a large databank of information that may be used by researchers to find out about cancer in the future. You will also be asked if we can keep any pieces of any tissue or cancer that may have been removed during your initial cancer surgery (if you had this). These are called tissue samples and may be used for future research. There are strict rules about keeping tissue samples. You can still take part in the study even if you do not want us to use your blood and tissue samples. More information about sample collection is given in Part 2. Expenses and payments We are unable to pay you for taking part in the research. You may incur some minor expenses if you take part, such as the cost of car parking for more frequent hospital visits. We will try and keep these to an absolute minimum and we will reimburse you for any additional travel expenses, if requested. What will I have to do? If you agree to take part, you will be asked to attend your scheduled visits (treatment and follow-up) which may be more frequent than if you are not on the study. You will also be asked to give an extra blood sample on 3 or 4 occasions and you will be asked to fill in some questionnaires to monitor your well-being and any financial implications of the study on 7 occasions. If you have a DVT, you will also need to have an additional ultrasound scan to see if you need to continue treatment for longer than 6 months. What are the potential disadvantages and risks of taking part? You will be asked to complete questionnaires which will take some time over and above your usual hospital/gp visits. The additional blood samples will be taken when you have standard blood tests and therefore should not cause you any additional discomfort. select-d PIL v2.0; 05-Apr-2013 5
Before participating in the research, you should consider if your participation will affect any insurance you may have and seek advice if necessary. There are certain side-effects to the drugs used in the study (although these will be the same if you are received drugs as standard treatment not in a trial). These are detailed below: Side-effects of treatment The side-effects of dalteparin and rivaroxaban are similar and the most serious is unusual or excessive bleeding or bruising. You will be given details of what to look out for and who to contact if you have any side-effects when you receive your treatment. However, if you have any bleeding that will not stop or is not normal for you (for example, a severe nose bleed or blood when you cough or go to the toilet) you must inform your doctor or nurse immediately. Participants who receive dalteparin may also experience discomfort at the injection sites. Possible risks to the unborn child The risks of anti-coagulant therapy on the unborn child are not fully known. It is therefore strongly advised that all people taking anticoagulants in the select-d trial use a reliable method of contraception during treatment and for six months afterwards, if they or their partner has the potential to conceive a baby. If you think you or your partner may be pregnant, you must inform your doctor or nurse immediately. Reliable methods of contraception include hormonal methods, such as the pill or implant, coils and condoms or caps with spermicide. Please speak to your doctor or nurse if you have any questions or concerns about this. What are the possible benefits of taking part? We cannot tell if the study will help you personally but the information we get from this study may help to improve the treatment of people with cancer in the future. select-d PIL v2.0; 05-Apr-2013 6
What if there is a problem? Any complaint you have will be addressed. More information will be given to you later in this document. What happens if I don t want to carry on with the study? If you withdraw or are unable to continue the study for any reason, we will only use the information that you have already given us to that point, unless you ask us to remove all your information (this may include your blood and tissue samples and questionnaires, if you wish). You may be asked to sign an additional form to confirm your wishes. Will my taking part in this study be kept confidential? Yes. All the information about your participation in this study will be kept confidential. The details are included in Part 2. Contacts for further information Your local contact for the study is: [INSERT NAME] [INSERT CONTACT DETAILS] Local Researcher: [Insert name and contact details of local investigator] Further information about research and about your type of cancer can be found at: http://www.cancerhelp.org.uk/ This completes Part 1 of the Information Leaflet. If the information in Part 1 has interested you and you are considering participation, please continue to read the additional information in Part 2 before making your decision. select-d PIL v2.0; 05-Apr-2013 7
Patient Information Leaflet: Part 2 select-d Anticoagulation Therapy in SELECTeD Cancer Participants at Risk of Recurrence of Venous Thromboembolism What if new information becomes available about clot treatment while I am on the trial? Sometimes we get new information about the treatment being studied. If this happens, your doctor will discuss this with you and decide whether or not you should continue in the study. If you decide not to continue, your doctor will make arrangements for your future care. If you do continue in the study, you may be asked to read a new Information leaflet and sign a new consent form. In the unlikely event of the study stopping before the end of your treatment, you will be treated according to the usual procedures at your hospital and in consultation with your doctor. Your progress will be followed in the same way as discussed earlier. What if there is a problem? If you are unsatisfied with the treatment that you receive by any member of staff (doctor, nurse etc.) you have the same rights as any NHS patient to voice and register your complaints through the hospital complaints procedure. If you have a complaint in relation to the study, you can contact the University of Warwick Deputy Registrar, Ms Joanna Horsburgh, by telephone: +44 (0)2476522713, email: J.Horsburgh@warwick.ac.uk or at: Ms J Horsburgh, Deputy Registrar s Office, University of Warwick, Coventry, CV4 8UW, United Kingdom. If you wish to complain formally, you can do this through the NHS Complaints Procedure. The person to be contacted for this is [Insert local complaints manager contact details]. In the event that something does go wrong and you are harmed during the research due to someone s negligence then you may have grounds for a legal action for compensation but you may have to pay your own legal costs. select-d PIL v2.0; 05-Apr-2013 8
Will information about me be kept confidential? Yes; we will follow professional, ethical and legal practice and all information which is collected about you during the course of the research will be kept strictly confidential. Information held by the NHS (such as your hospital number and date of birth) and records maintained by the General Register Office may be used to follow your health status. Any information about you which leaves the hospital will have your name and address removed so that you cannot be identified. Data collected for the study will be coded and the Chief Investigator will act as custodian of the data and regulate access. Authorised persons (e.g. representatives from the Sponsor, regulatory authorities and Research & Development departments) may need to look at information collected about you, including your medical notes. Confidentiality will be maintained at all times. With your permission, your GP will be notified that you are taking part in this study. He/she will be provided with a copy of this Patient Information Leaflet. What will happen to any samples I give? As mentioned in Part 1, we will request blood and tissue samples from you. If you give consent for us to collect these, they will be stored and used for future research about cancer which may take place within or outside the UK. The information attached to these samples will never include your name or address or any information that can identify you personally. Will any genetic tests be done on any of the samples I give? If you give consent for your blood and tissue samples to be used for other research projects they may include genetic tests. These studies will be approved by an ethics committee now or in the future before any blood or tissue is used. The genetic tests will not predict your personal risk of inheritance and they will have no effect on your insurance or other financial risks. The tests are usually those that help us understand how cancers and blood clots develop and how we can diagnose and treat them better. You can refuse to have your samples used in this way if you wish, without it affecting your participation in the study. select-d PIL v2.0; 05-Apr-2013 9
What will happen to the results of the research study? The results of the research will be published in scientific journals over the next few years. You will not be identified in person in any report or publication arising out of this study. If you wish, you can request a summary of the main results of the study when available. We will keep your health care provider informed of the study progress and they will be pleased to let you or your family know about the study outcome if you would like. Who is organising and funding the research? The research is being co-ordinated by the Warwick Clinical Trials Unit, based at the University of Warwick. The University of Warwick is the Sponsor for this study. The study is funded by Bayer plc. Who has reviewed the study? The study has been reviewed and given a favourable opinion by the West Midlands Coventry and Warwickshire Ethics Committee and the Medicines and Healthcare Products Regulatory Agency (MHRA). We have also worked with patient representatives who have regularly reviewed the study protocol and will continue to work with us throughout the study. What to do if you wish to take part in the study? If you wish to participate in this study you will be asked to sign a consent form after discussion with the researcher. You will also be given a copy of this information leaflet and a signed copy of the consent form to keep. If you decide that you do not want to take part, it will have no effect on any treatment or care that you will receive. Thank you for taking time to read this information leaflet and for considering the study. select-d PIL v2.0; 05-Apr-2013 10