CONSENT TO ACT AS A PARTICIPANT IN A RESEARCH STUDY. Vivek Reddy, MD 811 Kaufmann Medical Building 3471 Fifth Avenue Pittsburgh, PA

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1 CONSENT TO ACT AS A PARTICIPANT IN A RESEARCH STUDY TITLE: POINT: Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke PRINCIPAL INVESTIGATOR: Vivek Reddy, MD 811 Kaufmann Medical Building 3471 Fifth Avenue Pittsburgh, PA CO-INVESTIGATORS: Tudor Jovin, MD Chritopher Streib, MD Deepak Gulati, MD Maxim Hammer, MD Srikant Rangaraju, MD Marcelo Rocha, MD Ashutosh Jadhav, MD Jonathan Elmer, MD Matthew Starr, MD Dan-Victor Giurgiutiu, MD Lillian Emlet, MD R. Viktoria Totoraitis Bradley Molyneaux, MD Nima Aghaebrahim, MD David Campbell, MD University of Pittsburgh, Department of Neurology 811 Kaufmann Medical Building 3471 Fifth Avenue Pittsburgh, PA Clif Callaway, MD Jon Rittenberger, MD Frank Guyette, MD Ankur Doshi, MD Alexandra Weissman, MD University of Pittsburgh, Department of Emergency Medicine SOURCE OF SUPPORT: National Institutes of Health- National Institute of Neurological Disorders and Stroke (NIH-NINDS) The National Institute of Neurological Disorders and Stroke (NINDS) and the University of Pittsburgh Medical Center are conducting a research study known as a clinical trial. Page 1 of 16

2 Your study doctor and coordinator will explain to you the details of what is involved in the clinical trial. This document is designed to help you understand what will happen in the study, why the study is being done, what the study investigators hope to accomplish, and what risks or benefits might be involved in the study. Clinical trials include only people who choose to take part. Please take your time in deciding whether you want to be involved in the clinical trial. You are encouraged to discuss your decision with your friends and family. You can also discuss it with your health care team. If you have any questions, you should ask your study doctor or coordinator for more explanation. If you decide to do this study, you will be asked to sign and date this form. A description of this research study is available on as required by U.S. law. This website does not include information that can identify you; at most, the website will include a summary of the study results. You can search this website at any time. Who is being asked to take part in this research study? You are being asked to participate in this research study because you have just had a transient ischemic attack (TIA) or a minor stroke. A TIA is a condition that produces stroke-like symptoms like sudden weakness on one side of the body or trouble speaking, but the symptoms are temporary. A total of 5840 patients in about 350 hospitals will participate in this research study, with about 50 people enrolled at UPMC. Why is this research being done? The purpose of this study is to determine the safety and effectiveness of the combination of low-dose aspirin and a medication called clopidogrel (also known by the brand name Plavix ) in reducing the risk of stroke, heart attacks and other complications in patients who have just had a TIA or minor ischemic stroke. Patients who have had a TIA have a higher risk of developing a stroke. Recognizing and treating TIAs can reduce your risk of a stroke. Often, medication to prevent blood clots from forming is used to prevent a stroke in patients with blockage of one of the arteries in the brain. Low-dose aspirin has been shown to be effective in preventing strokes and heart attacks in patients who have had a TIA. Clopidogrel is another medication that is used to prevent strokes and heart attacks in patients at risk for these problems. Clopidogrel is a type of medication called an antiplatelet drug, and it works by helping to Page 2 of 16

3 keep platelets (small blood cells needed for normal blood clotting) in the blood from sticking together and forming harmful blood clots. This helps your blood flow more easily, and provides more protection against a future heart attack or stroke. Clopidogrel is approved for the prevention of a second stroke, and is taken once per day. Aspirin has also been shown to be effective in helping to prevent a second stroke or TIA, and is approved in doses ranging from 50 to 325 mg per day. Several studies that tested the combination of clopidogrel and aspirin have suggested that taking these two medications together may protect patients even more from major stroke and heart attack after a TIA or minor stroke, in comparison to taking aspirin alone, but these studies were small and the risk of bleeding was increased. The POINT trial has been designed to find out whether the combination of aspirin and clopidogrel reduces the risk of stroke, heart attacks and other complications compared to aspirin alone in patients like you. What procedures will be performed for research purposes? Before you begin the main part of the study... If you agree to take part in this study and sign this consent, you will be assessed to see if you meet the entry criteria for the study. In addition to the tests and exams performed as part of your routine care, your treating physician will also check whether or not you are eligible to participate in the study by performing the following: 1. A complete physical examination and medical history, including any medications you are currently taking, since there are some medications you cannot take while you are in this study. 2. A neurological evaluation using either the NIH Stroke Scale (NIHSS) or the ABCD 2 score. (If you have already had a physical examination and neurological assessment as part of your routine care, they may not need to be repeated for the study. If they were not done, or need to be repeated, the examination and neurological assessment will be done at no cost to you.) 3. If you are female and not post-menopausal or have not had a prior hysterectomy, you will undergo a urine or blood serum test to determine if you are pregnant. The drugs in this study can affect a fetus, so pregnant women may not participate in this study. You may not be enrolled in this study until all of these tests and procedures have been completed, and a study doctor has reviewed the results. During the main part of the study After those procedures are completed, and it has been determined that you are eligible for this study, you will be randomly assigned to one of the two groups described below. Page 3 of 16

4 Randomization means that you are put into a group by chance. You will have an equal chance of being placed in one of the two groups. This is a double-blind study, which means that neither your study doctor nor you will know which of the study drug groups you will be randomly assigned to. However, this information will be available in the case of an emergency. Group 1: If you are assigned to this group, you will take an initial dose of 600mg of clopidogrel on the first day of your participation in the study (8 tablets of 75mg each) and then you will take 75mg (1 tablet) of clopidogrel each day for the next 89 days. You will also take mg of aspirin each day for 90 days; the dose of aspirin will be determined by your treating physician. OR Group 2: If you are assigned to this group, you will take an initial dose of 8 tablets of placebo, a tablet containing an inactive substance, on the first day of your participation in the study, and then 1 tablet of placebo each day for the next 89 days. You will also take mg of aspirin each day for 90 days; the dose of aspirin will be determined by your treating physician. The current accepted treatment for stroke prevention is aspirin. Just before your discharge from the hospital, an appointment for your next visit in about 90 days will be made and information about how to contact your study doctor in case of an emergency will be given to you. You will be asked for your contact information, such as your address and any alternative contacts, so that we can keep in touch with you throughout the study. You can choose not to provide alternative contacts. Study Visits: One Week About 1 week after your first dose, the Study Coordinator will call you or ask you in person whether you ve been taking your study medications, and collect information about any side effects or possible events you might be experiencing that are associated with the study medication. The Coordinator will also collect information about your other medications and will ask you to complete a short survey about any neurological symptoms you may have had since your discharge. 30 Day Telephone Contact About 30 days after your first dose, the Study Coordinator will contact you to ask you whether you ve been taking your study medications, and whether you are experiencing any side effects or other possible adverse events. Event Visit If it is thought that, based on information you provide, you might have had a stroke, TIA Page 4 of 16

5 or heart attack, you will be scheduled for an evaluation. At the visit, you will: answer any questions about your study medications and any side effects or adverse events be evaluated using two scales, the modified Rankin Scale (mrs) and the NIH Stroke Scale (NIHSS) have your blood pressure taken complete another survey about any neurological symptoms you may have had since enrolling in the study. 90 Days You will need to return to UPMC for a study visit 90 days after starting the study. At the follow-up visit you will: answer questions about your study medications and any side effects or adverse events be evaluated using the modified Rankin Scale (mrs) and the NIH Stroke Scale (NIHSS) have your blood pressure taken complete another survey about any neurological symptoms you may have had since enrolling in the study If the visit is done by telephone, then you will: answer questions about your study medications and any side effects or adverse events be evaluated using the modified Rankin Scale complete the Stroke-Free and the Morisky Questionnaires At the end of the study, your treating physician will discuss with you the best choice for antiplatelet drugs like those in the study. Depending on costs, side effects, and your own preferences, clopidogrel, aspirin, or the medication aspirin/dipyridamole (also known as Aggrenox ) may be the best choice. If for some reason we are unable to locate you for the 90 Day follow up visit, we will ask your alternate contact and/or review your medical chart to find out if you have been seen by another doctor within your hospital system and if you have had a stroke, TIA, or heart attack during the 90-Day follow up period. In order to make sure that we include the full 90-Day period in our review, we will need to review your chart after the 90 day study period has ended. This means that we may continue to collect information about you up to 150 days from your enrollment. The total length of your participation in this study is approximately 3 months. The amount of time needed to evaluate you and assign you to a treatment group is about 2 hours. The telephone follow-up at day 7 will take about 15 minutes. The telephone Page 5 of 16

6 contact at day 30 will take about 15 minutes. The follow-up visit at 90 days after your discharge from the hospital will take about 1 hour or less if completed by telephone. About 2 hours will be needed if you are scheduled for an in-person evaluation. Therefore, a total of about 4-5additional hours of participation will be needed from you if you join the study. About 2 hours will be needed if you are scheduled for an evaluation because it is thought that you might have had a stroke, TIA or heart attack. What are the possible risks, side effects, and discomforts of this research study? You may have side effects while on the study. Everyone taking part in the study will be watched carefully for any side effects. However, not all the side effects that may happen are known. Side effects may be mild or very serious. Your health care team may give you medicines to help lessen side effects. Many side effects go away soon after you stop taking the study drugs; in some cases, side effects can be serious, long lasting, or may never go away. You should talk to your study doctor about any side effects you experience while taking part in the study. Risks and side effects include: 1. Randomization: You will be randomly assigned to a study group, with an equal (50:50) chance of being assigned to a study group. The treatment you receive may prove to be less effective or to have more side effects than the other study treatment or than other available treatments. This will not be known until after the study is completed and the data have been analyzed. Placebo risks: If you are in the group that receives placebo, your condition will go without the active (study) treatment for about 12 weeks. If you are already taking aspirin and clopidogrel, or if your medical institution commonly treats this condition with aspirin and clopidogrel and you are randomized to the group taking placebo, then you will actually receive less treatment on the study than you would off the study. This could increase your risk of stroke compared to not participating in the study. This will not be known until after the study is completed and the data have been analyzed. However, you will continue receiving aspirin if you are assigned to the group that receives placebo. 2. Side effects from study drugs: All medications have possible risks and side effects, even those that have been approved by the US Food and Drug Administration (FDA). Known side effects of each of the study medications are listed below. Patients who have a known hypersensitivity (allergic reaction) to any of the study medications should not participate in this study. Side effects from clopidogrel: Clopidogrel works by thinning the blood in order to help blood flow more easily. Since blood clotting may take longer than normal while you re taking clopidogrel, you may experience longer bleeding from cuts, and you may also bruise more easily. You should tell your study doctor promptly if you Page 6 of 16

7 experience any unexplained bruising or unusual bleeding (e.g., bleeding from an unusual site or that takes a very long time to stop), particularly if also accompanied by a fever, signs of infections, extreme tiredness or feeling generally unwell. Superficial and internal bleeding, including bleeding into the brain, are also side effects of clopidogrel; internal bleeding and bleeding into the brain are serious conditions that can result in death. The most common side effects of clopidogrel include abdominal or stomach pain, diarrhea, skin reactions (rash, itching), aching muscles and/or joints, dizziness, fever, headache and a decrease in the number of a type of white blood cell called a neutrophil. In rare cases, clopidogrel may cause stomach bleeding; symptoms of stomach bleeding include darker (sometimes black), tarry stools and stomach pain. There have also been rare reports of a serious bleeding disorder called thrombotic thrombocytopenic purpura (TTP) associated with clopidogrel; this side effect is most likely to occur during the first two weeks of treatment. During the trial, you must immediately tell your study doctor about any abnormal or unexpected events and in particular about any warning sign of brain attack (feeling weak, or numb on one side, blurry vision, or no vision usually in one eye, unable to talk clearly, dizziness or falling, or severe headache), any anginal pain (chest pain during rest or exercise), any bleeding (overt bleeding, spontaneous bruise), infection (fever, shivering, sore throat), skin rash, severe diarrhea, or jaundice (yellow discoloration of the skin). If you are hospitalized in a hospital where the study doctor does not work, whatever the reason is, you (or one of your relatives) must inform your study doctor as soon as possible. You must also tell your primary care doctor that you are taking part in this study. Side effects from aspirin: Aspirin has two main types of side effects: it can cause gastrointestinal upset and it can increase bleeding. The most common side effects associated with aspirin use are gastrointestinal-related, and include stomach pain, heartburn, nausea and/or vomiting. In rare cases, more serious effects, such as bleeding, have been observed in individuals taking aspirin for extended periods of time. Even less commonly, hemorrhagic stroke (bleeding in the brain) can occur. The side effects of aspirin are generally dose-related, and tend to occur more often in doses that are higher than the dose of aspirin taken in this study. Side effects from aspirin and clopidogrel: The biggest risk in this study is bleeding resulting from the combination of aspirin and clopidogrel. This combination has not been tested right after a TIA or minor ischemic stroke, so rates of bleeding must be estimated from other studies of stroke and acute coronary syndromes such as heart attack and unstable angina or chest pain. It is likely, based on the results of those studies, that clopidogrel combined with aspirin is associated with a slightly higher risk of major Page 7 of 16

8 bleeding. The combination of aspirin and clopidogrel may increase the risk of complications with surgeries or other procedures, such as endarterectomy (a surgical procedure to remove material called plaque from inside an artery), or may delay the performance of these procedures due to concerns about bleeding risk; a delay could increase your risk of stroke. Side effects from discontinuing medications for study purposes: If you are currently taking a drug that blocks platelets (such as clopidogrel or dipyridamole) or blocks clotting (such as warfarin), this drug will be stopped before you enter the study; if you have a reason to be on one of these specific drugs, your doctor will not enroll you in this trial. Also, some doctors treat patients with TIA with clopidogrel and aspirin together. In this trial, there is a risk that you will receive weaker drugs than you would have gotten otherwise, and this could increase your risk of having a stroke but it could also reduce your risk of bleeding. This will not be known until after the study is completed and the data have been analyzed. Risks of blood draws: The risks and discomforts of drawing blood include temporary discomfort from the needle stick, the possibility of pain or bruising at the site of the blood draw, occasional feelings of lightheadedness and, rarely, infection at the site of the blood draw. Pregnant or nursing females: Because participation in this study may harm a pregnancy, you must not become pregnant or father a child while you are in this study. If so, you must tell your doctor at once. Acceptable methods of birth control include hormonal contraceptives, intrauterine device, abstinence, or spermacide and barrier. Also, women must not breast feed while in this study. If you are a woman and you are able to become pregnant, you will have a urine or blood serum test to make sure that you are not pregnant before you are permitted to undergo the experimental procedures. If you have questions, you are encouraged to speak with either the study doctor or your personal physician. Confidentiality: Participation in research will mean a loss of confidentiality, but information about you will be handled as confidentially as possible. Unknown Risks: The experimental treatments may have side effects that no one knows about yet. The researchers will let you know if they learn anything that might make you change your mind about participating in the study. For more information about risks and side effects, ask your study doctor. What are possible benefits from taking part in this study? Page 8 of 16

9 There is no guarantee that you will benefit from joining this study. If you are in the group that receives clopidogrel and it proves to treat your condition more effectively and with fewer side effects than the placebo, you may benefit from your participation. Your participation in the study may help the investigators better understand the safety and effectiveness of clopidogrel when used with aspirin to prevent stroke in patients with a TIA or a minor ischemic stroke, and the knowledge gained from participation in this research study may help other patients with TIA or minor ischemic stroke in the future. What treatments or procedures are available if I decide not to take part in this research study? If you choose to not take part in this study, you will be given the same care according to standard medical practices that you would normally receive upon entering the ED. Please talk to the study doctor, study coordinator, or your treating doctor if you have questions about your options. You do not have to be in this study to be treated for your condition. If you do not want to join this study, you will get the usual therapies that your treating physician prescribes following a TIA or minor ischemic stroke. There are several drugs approved by the FDA for the prevention of a stroke, including aspirin and clopodigrel. Aspirin is available without a prescription, and clopidogrel is available off the study; your primary care doctor may prescribe aspirin and clopidogrel together to treat your condition. Other drugs are available to you by prescription from your primary care doctor without participating in this study. You may also choose not to receive any treatment. You may wish to discuss your treatment options with your primary care doctor before you decide to participate in this study. If I agree to take part in this research study, will I be told of any new risks that may be found during the course of the study? We will promptly notify you if any new information develops during the course of this study that could cause you to change your mind about continuing to participate in this study. Page 9 of 16

10 Will my insurance provider or I be charged for the costs of any procedures performed as part of this research study? You will not be required to pay any extra money because of this study, but you will be responsible for the costs of the standard care for your condition. The study will pay for the study treatment medicine that is not standard care and for the materials for the extra research blood tests needed. The study will also pay for the follow-up visits related to the study. The normal costs of taking care of you for your stroke will have to be paid for by you or your insurance company. These costs are the same as you would be responsible for if you were not in this research study. Will I be paid if I take part in this research study? You will not be paid to participate in this study. Who will pay if I am injured as a result of taking part in this study? If you believe that the research procedures have resulted in an injury to you, immediately contact the Principal Investigator on the first page of this form. Emergency medical treatment for injuries solely and directly related to your participation in this research study will be provided to you by the hospitals of UPMC. Your insurance provider may be billed for the costs of this emergency treatment, but none of those costs will be charged directly to you. If your research-related injury requires medical care beyond this emergency treatment, you will be responsible for the costs of this follow-up care. At this time, there is no plan for any additional financial compensation. Who will know about my participation in this research study? Any information about you obtained from this research will be kept as confidential (private) as possible. All records related to your involvement in this research study will be stored in a locked file cabinet or password-protected computer database that only authorized study personnel can access. Your identity on these records will be indicated by a case number rather than by your name, and the information linking these case numbers with your identity will be kept separate from the research records. Your research results will be sent to researchers at NETT and the NINDS so they can analyze the study results and monitor the conduct of the study. Your information will be coded and sent electronically without your name or other information that may reveal your identity. You will not be identified by name in any publication of the research results unless you sign a separate consent form giving your permission (release). Page 10 of 16

11 Will this research study involve the use or disclosure of my identifiable medical information? This research study will involve the recording of current and future identifiable medical record information from your hospital and physician office records. The information that will be recorded will be limited to information concerning your evaluation for stroke. This information will be used to see if you are eligible for this study, what caused your symptoms, and what happened to you medically after your ED evaluation. This research study will result in identifiable information that will be placed into your medical record held at University of Pittsburgh Medical Center. The nature of the identifiable information resulting from your participation in this research study that will be recorded in your medical record includes: the fact that you participated in a research study, results of your CT scan, blood and urine tests and pregnancy test, if appropriate, and whether you were admitted to the hospital or discharged from the ED. Who will have access to identifiable information related to my participation in this research study? In addition to the investigators listed on the first page of this authorization (consent) form and their research staff, the following people may have access to your chart and research records: Authorized representatives of the University of Pittsburgh Research Conduct and Compliance Office may review your identifiable research information (which may include your identifiable medical record information) for the purpose of monitoring the appropriate conduct of this research study. Authorized representatives of the sponsor of this research study, the NINDS, and the NETT coordinating center will review and/or obtain identifiable information (which may include your identifiable medical information) related to your participation in this research study for the purpose of monitoring the accuracy and completeness of the research data and for performing required scientific analyses of the research data. In addition, representatives from the NINDS Clinical Research Collaboration (CRC) Operations Center, Neurological Emergencies Treatment Trials (NETT) Network (University of Michigan), the Statistical Data Management Center (prenancy; and the Medical University of South Carolina) may review information about you to check on the study. If you sign this consent form, you are allowing the study sponsor, the University of California (UCSF), and the FDA to review your medical records. Your name will not be used in any published reports about this study, and you will only be identified by a number in study records. Paper records will be kept in a locked file cabinet in a secure room, and computerized records will be kept on a secure server accessible only by Page 11 of 16

12 authorized members of the study team. At your request, information collected about you from your participation in this study will be given to your primary care doctor. While these representatives understand the importance of maintaining the confidentiality of your data, the UPMC and University of Pittsburgh cannot guarantee the confidentiality of this information after it has been obtained by the study sponsor and coordinating center. Authorized representatives of the U.S. Food and Drug Administration may review and/or obtain identifiable information (which may include your identifiable medical information) related to your participation in this research study for the purpose of monitoring the accuracy of the research data. While the U.S. Food and Drug Administration understands the importance of maintaining the confidentiality of your identifiable research and medical information, the University of Pittsburgh and UPMC cannot guarantee the confidentiality of this information after it has been obtained by the U.S. Food and Drug Administration. Authorized representatives of the UPMC hospitals or other affiliated health care providers may have access to identifiable information (which may include your identifiable medical information) related to your participation in this research study for the purpose of (1) fulfilling orders, made by the investigators, for hospital and health care services (e.g., laboratory tests, diagnostic procedures) associated with research study participation; (2) addressing correct payment for tests and procedures ordered by the investigators; and/or (3) for internal hospital operations (i.e. quality assurance). In unusual cases, the investigators may be required to release identifiable information (which may include your identifiable medical information) related to your participation in this research study in response to an order from a court of law. If the investigators learn that you or someone with whom you are involved is in serious danger or potential harm, they will need to inform, as required by Pennsylvania law, the appropriate agencies. For how long will the investigators be permitted to use and disclose identifiable information related to my participation in this research study? The investigators may continue to use and disclose, for the purposes described above, identifiable information (which may include your identifiable medical information) related to your participation in this research study for a minimum of six years after final reporting or publication of a project. May I have access to my medical information that results from my participation in this research study? Page 12 of 16

13 In accordance with the UPMC Notices of Privacy Practices document that you have been provided, you are permitted access to information (including information resulting from your participation in this research study) contained within your medical records filed with your health care provider. Is my participation in this research study voluntary? Your participation in this research study, including the use and disclosure of your identifiable information for the purposes described above, is completely voluntary. (Note, however, that if you do not provide your consent for the use and disclosure of your identifiable information for the purposes described above, you will not be allowed to participate in the research study.) Whether or not you provide your consent for participation in this research study will have no effect on your current or future relationship with the University of Pittsburgh. Your decision to participate or not will have no effect on your current and future medical care at a UPMC hospital or affiliated health care provider or your current or future relationship with a health care insurance provider. Your doctor may be involved as an investigator in this research study. As both your doctor and research investigator, s/he is interested both in your medical care and the conduct of this research study. Before agreeing to participate in this research study, or at any time during your study participation, you may discuss your care with another doctor who is not associated with this research study. You are not under any obligation to participate in any research study offered by your doctor. May I withdraw, at a future date, my consent for participation in this research study? You may withdraw, at any time, your consent for participation in this research study, to include the use and disclosure of your identifiable information for the purposes described above. (Note, however, that if you withdraw your consent for the use and disclosure of your identifiable medical record information for the purposes described above, you will also be withdrawn from further participation in this research study.) Any identifiable research or medical information recorded for, or resulting from, your participation in this research study prior to the time you formally withdraw your consent may continue to be used and disclosed by investigators for the purposes described above. To formally withdraw your consent for participation in this research study, you should tell the staff or provide a written and dated notice of this decision to the Principal Investigator of this research study at the address listed on the first page of this form. Page 13 of 16

14 If you want to stop being in the study, it will have no effect on your current or future relationship or medical care with your insurer, your doctor, the University of Pittsburgh, or any UPMC hospital or affiliated health care provider. If I agree to take part in this research study, can I be removed from the study without my consent? At any time, the study doctor may discontinue your participation in this study. The study doctor may decide to take you off this study if your health or safety may be at risk, you have not been following study instructions or because of a study administrative decision by the study sponsor or the study doctor. **************************************************************************************************** VOLUNTARY CONSENT The above information has been explained to me and all of my current questions have been answered. I understand that I am encouraged to ask questions, voice concerns or complaints about any aspect of this research study during the course of this study, and that such future questions, concerns or complaints will be answered by a qualified individual or by the investigator(s) listed on the first page of this consent document at the telephone number(s) given. I understand that I may always request that my questions, concerns or complaints be addressed by a listed investigator. I understand that I may contact the Human Subjects Protection Advocate of the IRB Office, University of Pittsburgh ( ) to discuss problems, concerns, and questions; obtain information; offer input; or discuss situations in the event that the research team is unavailable. By signing this form I consent to participate in this research study and provide my authorization to share my medical records with the research team. A copy of this consent form will be given to me. Participant s Signature Printed Name of Participant Date/Time Alternative Contacts Please place your initials in the YES box to the right, if you agree to allow study team members to contact your alternative contacts to discuss your participation in this study and find out how you are doing at the 90 Day visit, if we are unable to reach you. YES Page 14 of 16

15 Optional POINT Biomarkers Ancillary Study If you take part in the main study, you will also be asked for an optional one-time blood sample as part of an ancillary, or secondary, study of biomarkers. Biomarkers are molecules found in blood, other body fluids, or tissues that are signs of a specific condition or disease. If you agree to participate in the secondary study, we will collect about 2 teaspoons of blood (two 5 ml tubes) from you for a type of test called a biomarker test on your blood. The biomarker test will help us learn if you have specific biomarkers for the genes named ABCB1 and CYP2C19 which may affect how your body responds to being treated with clopidogrel, the medication being studied in this trial. The results of the biomarker tests can help us learn more about how effective clopidogrel can be for preventing stroke in people who have had a TIA and also have those specific biomarkers in their blood. The blood will be prepared for genetic analysis and stored at the Neurogenetics Laboratory at the Mayo Clinic in Jacksonville, Florida (MCF) for 20 years. The stored blood samples may be used in future studies for TIA and stroke. We will do our best to make sure that the personal information that we have collected is kept private. We will assign numbers to label the blood samples and no personal information will be on the tubes used to store the blood samples. The genetic test results will be provided to the Principal Investigator and statistician in the study. You will not receive the genetic test results. The secondary study is optional and you can decide to participate in just the main study. You can decide to stop participating in the secondary study at any time by letting your study doctor know and your blood sample will be destroyed. Please indicate if you wish to also participate in the optional ancillary study by reading each sentence below and entering your initials in the "Yes" box. If you have any questions about the optional ancillary study, please talk to the study doctor or nurse. No matter what you decide to do, it will not affect your care. 1. My blood sample may be taken for this research, as described in the Optional POINT Biomarkers Ancillary Study section above. YES YES Page 15 of 16

16 2. My blood sample may be kept for use in research to learn about biomarkers related to TIA and stroke. CERTIFICATION OF INFORMED CONSENT: I certify that I have explained the nature and purpose of this research study to the above-named individual(s), and I have discussed the potential benefits and possible risks of study participation. Any questions the individual(s) have about this study have been answered, and we will always be available to address future questions, concerns or complaints as they arise. I further certify that no research component of this protocol was begun until after this consent form was signed. Investigator s Name (Print) Investigator s Signature Date/Time Page 16 of 16