School of Medicine Department of Emergency Medicine Iroquois Building, Suite 400A 3600 Forbes Avenue Pittsburgh, PA 15261 412-647-3078 CONSENT TO PARTICIPATE IN A RESEARCH STUDY TITLE: Amantadine to Stimulate Wakefulness Following Post-Anoxic Encephalopathy Principal Investigator: Jon Rittenberger, MD, MS (412) 647-3078 Co-Principal Investigators: Clifton Callaway, MD, PhD; Ankur Doshi, MD; Adam Frisch, MD; Francis Guyette, MD; Alexandra Weissman, MD; Kelly Sawyer, MD; Mashashi Okubo, MD; Department of Emergency Medicine (412) 647-3078 Bradley Molyneaux, MD; Cameron Dezfulian, MD; Jonathan Elmer, MD; Lillian Emlet, MD, Department of Critical Care Medicine (412)-647-6249 Zohaib Akhtar, MD; Ciaran Cunningham, MD; Riaz Rahman, MD; Department of Internal Medicine (412) 232-5533 Source of Support: American Heart Association Why is this study being done? Your loved one has experienced a serious medical situation called cardiac arrest a condition where the heart stops beating, and which leads to death unless treated immediately. The main purpose of this study is to test the effects of amantadine, a neurostimulant (drug that helps the brain become more active), on the rate of awakening for patients after they have had a cardiac arrest. Cardiac arrest is a very serious condition. You have already spoken to the provider about the different treatment options, which include lowering the body temperature, referred to as targeted temperature management (TTM). TTM has been shown to improve brain function following a cardiac arrest. Treating patients with TTM is now standard care in post cardiac arrest patients with poor brain function after the arrest. When you have a cardiac arrest, the organs in your body do not get enough oxygenated blood for a period of time. This lack of oxygen to the brain can lead to coma. One method to accelerate awakening from coma is the use of neurostimulant medications, such as amantadine. Amantadine is currently used and is FDA (Food and Drug Administration) approved for use in patients with Parkinson s Disease to help control muscle movements and help ease stiffness. It was previously used in the treatment of influenza. Amantadine has been used to stimulate wakefulness in other brain injury states such as traumatic brain injury; however, it is not FDA approved for this use. Page 1 of 8
How many people will take part in the study? This study is being performed at the University of Pittsburgh. The University of Pittsburgh plans to enroll approximately 120 subjects aged 18 years or older who have experienced cardiac arrest and are currently in a coma. What will happen if my loved one takes part in this research study? Screening Procedures: Screening procedures are tests and procedures that will be done to determine if your loved one is eligible to take part in the research study. For this research study, the screening procedures will be a review of the medical record to see if he/she qualifies for the study. Women who are pregnant are excluded from this study. Pregnancy is determined via a pregnancy test. Women of childbearing age will be required to undergo a pregnancy test. Research Procedures: Your loved one will be randomly assigned (like the flip of a coin) to receive either a set dose of amantadine or a placebo along with standard of care for 7 days. Your loved one will have a 1 in 2 chance of receiving either the study drug or the placebo. You will not be able to choose the study group to which he/she will be assigned. Depending upon the group to which your loved one is assigned, he/she may receive a placebo instead of the study drug. A placebo is an inactive solution that looks like the study drug, but a placebo contains no active medication. Placebos are used to help determine if the results of the study are truly from the study drug. Your loved one s provider/care team will be informed what group he/she is in. If one treatment arm is found to be less effective than the other while your loved one is taking part in the study, you will be informed and further treatment will be discussed. If your loved one qualifies to take part in this research study, he/she will undergo these research procedures: A. Study Drug Dosing: Your loved one will be administered either the amantadine 100 mg or the placebo by mouth or feeding tube once or twice a day for 7 days. The number of doses per day depends on how their kidneys are functioning. A feeding tube is placed in order to feed comatose patients as part of standard clinical care. B. Blood Draws: Blood draws will be performed for 4 days of study participation. The blood will be collected via a needle stick in his/her arm if there is not already an existing line in place. The blood is being collected to look at amantadine levels in your loved one s blood. We will collect 5 ml of blood at 8 time points during the study, for a total of 40mL (approximately 2 ½ tablespoons). We would also like to keep these samples for future testing on brain injury. The samples will be de-identified. That means that they will be assigned a code, and the information linking the code to your loved one s identity will be stored in a separate secure location. Page 2 of 8
C. Data Collection: We will record the following information that was obtained as part of your loved one s usual care (i.e. the measurements are not being done for research): a) We will record information about past medical history, including demographics (name/gender/ethnicity), the details of the cardiac arrest and all the emergency and hospital treatment that were received up until this point. b) Throughout participation, we will review your loved one s chart and record lab results, CT results, MRI results, and EEG results from his/her routine care. c) We will record vital signs (for example, heart rate, breathing rate, temperature, blood pressure). d) We may record information about the circumstances before your loved one was resuscitated, and the method in which he/she was resuscitated, as well as information about health history and medications that he/she takes on a regular basis. What side effects or risks can my loved one expect from being in the study? As with any experimental procedure, there may be adverse events or side effects that are currently unknown and certain of these unknown risks could be permanent, severe or lifethreatening. Amantadine Common: Amantadine may cause some people to have anxiety, agitation, neurvousness, and difficulty concentrating. It can cause headache, irritability, loss of appetite, nausea, trouble sleeping or nightmares. In some people a purplish, red, net-like rash has been noted. Infrequent: Amantadine may cause some people to have blurred vision, difficulty urinating, dizziness, lightheadedness, changes in vision or hearing, or swelling in the feed or lower legs. It can also cause constipation or diarrhea. Rare: In rare cases, amantadine has been shown to cause seizures. It rarely can cause a decrease in vision or difficult coordinating movements, fever, chills, sore thorat, shortness of breath, increased blood pressure, rash, slurred speech, throughts of suicide or attempts at suicide. Blood Draw Infrequent: The risks associated with venipuncture include momentary pain during needle insertion and bruising at the site of needle insertion. Infection, excess bleeding, clotting, and fainting also are possible, though unlikely. However, it is very likely that your loved one will have an intravenous line from which we may draw, and so the blood draw will be painless. Rare: There is a very small risk that air or microorganisms may be introduced in your loved one s blood stream, but many steps will be taken to keep this risk at an absolute minimum as blood draws will be aligned with clinical blood draws if feasible. Page 3 of 8
LOSS OF CONFIDENTIALITY There is the potential for loss of confidentiality by participating in this study. Every effort will be made to protect the confidentiality of your loved one s identifiable information. However, if his/her participation becomes known, it could create a problem or hardship for him/her depending upon the type of information disclosed. POSSIBLE BENEFITS It is not possible to predict whether your loved one will benefit directly from participation in this study. However, his/her participation may help others in the future as a result of knowledge gained from the research. What are the costs of taking part in this study? Your loved one will not be paid for participating in this study. Your loved one and his/her insurer or third party payer will not be billed for research-related services or services related solely to the research. However, your loved one, or his/her insurer, will be billed for all other usual care services, and/or services not connected with the study, just as he/she would if not in the study. What are the alternatives to participation in this study? If you decide to not participate in this study, your doctor will continue to treat your loved one according to their usual standard of care treatment plan. What happens if my loved one is injured because he/she took part in this study? If you believe that the research procedures have injured your loved one, immediately contact the Principal Investigator, Dr. Rittenberger. The hospitals of UPMC will provide emergency medical treatment for injuries solely and directly related to your loved one s participation in this research study. His/her insurance provider may be billed for the costs of this emergency treatment, but none of those costs will be charged directly to your loved one. If the research-related injury requires medical care beyond this emergency treatment, your loved one will be responsible for the costs of this follow-up care. At this time, there is no plan for any additional financial compensation. Will this research study involve the use or disclosure of my loved one s identifiable medical record information? This research study will involve the recording of past, current and/or future identifiable medical information from your loved one s hospital and/or other health care provider records. This information that will be recorded will be limited to information concerning treatment (e.g. diagnostic information, lab and scan results, medications, medical history). This information will be used to determine your loved one s eligibility for this study and to follow his/her response once you are enrolled in the study. This research study will result in identifiable information that will be placed into your loved one s medical records held at UPMC. The nature of the identifiable information resulting from your participation in this research study that will be recorded in your medical record includes diagnostic information, lab and scan results, response to study treatment including adverse events (side effects). Page 4 of 8
Who will have access to my loved one s identifiable medical record information related to my participation in this research study? In addition to the investigators listed on the first page of this consent form and their research staff, the following individuals will or may have access to identifiable information (which may include your loved one s identifiable medical record information) related to his/her participation in this research study: Authorized representatives of the University of Pittsburgh Research Conduct and Compliance Office may review identifiable research information (which may include identifiable medical record information) for the purpose of monitoring the appropriate conduct of this research study. Authorized representatives of the UPMC hospitals or other affiliated health care providers may have access to identifiable information (which may include identifiable medical information) related to your loved one s 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) assessing internal hospital operations (i.e. quality assurance). Authorized representative of the FDA and American Heart Association may have access to this information as well In unusual cases, the investigators may be required to release your loved one s identifiable research information (which may include identifiable medical record information) in response to an order from a court of law. If the investigators learn that your loved one or someone with whom he/she is involved is in serious danger or potential harm, they will need to inform the appropriate agencies, as required by Pennsylvania law. Who will know about my loved one s participation in this research study? Any information about your loved obtained from this research, including personal health information, will be kept as confidential (private) as possible under the law; however, absolute confidentiality cannot be guaranteed. All records and samples related to your loved one s involvement in this research will be stored in a secure location. Your loved one s identity on these records and the samples will be indicated by his/her subject identification number rather than by name, and the information linking the subject identification number with your loved one s identity will be kept separate from the research records. De-identified data and blood samples may be shared with other investigators; however, there will be no way for these investigators to determine your loved one s identity. Your loved one will not be identified by name in any publication of the research results or in any other scientific publications or presentations unless he/she signs a separate consent form giving your permission (release). Page 5 of 8
For how long will the investigators be permitted to use and disclose identifiable information related to my loved one s participation in this research study? The investigators may continue to use and disclose, for the purposes described above, identifiable information (which may include identifiable medical information) related to your loved one s participation in this research study for an indefinite period of time. May my loved one have access to his/her medical record information resulting from participating in this trial? In accordance with the UPMC Notices of Privacy Practices document that you have been provided, your loved one is permitted access to information (including information resulting from participation in this research study) contained within your loved one s medical records filed with his/her health care provider. Is my loved one s participation in this research study voluntary? Participation is completely voluntary and a decision to participate, or to later withdraw from the study, will not affect either your loved one s current or future medical care at UPMC. If you agree to have your loved one participate and later change your mind, or if he/she later decides to withdraw, a written and dated notice of this decision needs to be sent to the investigator. You and your loved one have the right to request that all information collected to date and/or the blood samples be destroyed. We will continue to use data already collected or analyzed, and we will store blood samples collected before he/she withdraws unless you specifically request these be destroyed. If the investigators or treating providers feel that your loved one cannot complete the study requirements safely, they may withdraw your loved one from the study. ******************************************************************** 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 (1-866-212-2668) 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 agree 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 Page 6 of 8
SURROGATE CONSENT is unable to provide direct consent for study participation because: Participant s Name (Print) Therefore, by signing this form, I give my consent for his/her participation in this research study. Representative s Name (Print) Representative s Signature Witness Signature Relationship to Participant Date/Time Date /Time CERTIFICATION OF INFORMED CONSENT: I certify that I have explained the nature and purpose of this research study to the abovenamed 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 7 of 8
CONSENT FOR CONTINUED RESEARCH PARTICIPATION: I understand that I am currently participating in a research study. Permission for my participation in this study was obtained initially from my authorized representative (surrogate) because of my inability to provide consent when initial permission was requested. I have now recovered to the point where I feel that I can provide direct consent for continued participation in this research study. The study has been described to me and all of my questions have been answered. I understand that I have the right to request that all information collected to date and /or my blood samples be destroyed. Any additional questions or concerns about any aspect of this study will be answered by the researchers. Questions I might have about my rights as a research participant will be answered by the Human Subject Protection Advocate at 1-866-212-2668. By signing below, I agree to continue my participation in this research study. A copy of this consent form will be given to me. Participant s Signature Participant s Name (Print) Date/Time Page 8 of 8