Appendix C: Informed Consent Form

Appendix C: Informed Consent Form

Consent for Participation in a Clinical Research Study

PROTOCOL NUMBER: XXXXXPROTOCOL TITLE: Surgery versus Medical Treatment Alone for Patients with Significant Mitral

Regurgitation and Non-ischemic Congestive Heart Failure: the SMMART-HF studyPROTOCOL VERSION / DATE: September 13, 2007

INTRODUCTION

This study is being sponsored by a grant from the National Heart, Lung, and Blood Institute (NHLBI), which is run by the U.S. government. Portions of [INSERT RCC’s PI NAME HERE] salary and his/her research team’s salaries are being paid by this grant.

You are being asked to participate in the study because you have an enlarged heart with a leaky mitral valve. It is currently unknown whether surgery to fix this leaky valve helps people feel better or live longer. This research study plans to enroll 120 patients in the United States and Canada. Half of the patients would be randomly assigned to receive mitral valve surgery at the beginning of the study. The other half of patients would be asked to wait at least 18 months before considering such surgery. The goal is to find out if this type of surgery is helpful in treating patients with leaky mitral valves. Your participation in this research study is completely voluntary.

PURPOSE OF THE STUDY

The purpose of this study is to determine if adding surgical mitral valve repair to regular treatment in patients with heart failure (1) improves heart function, (2) helps patients feel better, and (3) is safe. Mitral valve repair is not an experimental procedure.

BACKGROUND

Heart failure with an enlarged heart is a common medical problem. Approximately 4 out of 10 patients with such heart failure develop a leaky mitral valve. The reason for this mitral valve failure is thought to be directly related to the increased heart size. As the heart enlarges, it pulls the valve leaflets apart. The result is that the valve can no longer perform its normal function, and blood spills backward every time the heart beats.

Allowing blood to flow backward is thought to make an already weak heart even weaker. The presence of a leaky mitral valve in patients with heart disease is associated with shorter survival. Whether patients do worse because of the leaky valve is unknown; it is possible that leaky valves only indicate worse heart failure but do not actually cause death.

Current available therapies Fortunately, a few medications used to treat heart failure have been shown to decrease leaking of the mitral valve and slow the progression of heart failure. These include ACE inhibitors which lower blood pressure (for example, captopril, lisinopril, and enalapril), nitrates (isosorbide dinitrate), and beta-blockers (carvedilol, and metoprolol). Placement of a special pacemaker that triggers both sides of the heart at the same time (called cardiac re-synchronization therapy or bi-ventricular pacing) has also been shown to decrease the leaking of the mitral valve in patients with heart failure. You are probably taking some of these drugs.

September 13, 2007 Patient Initials______ Page 1 of 8

Surgical treatment for leaky mitral valves in patients with heart failure usually consists of placement of an artificial ring around the valve. These rings tighten up the mitral valve, bringing the valve leaflets closer together so that they close better and prevent backflow of blood.

Romano and Bolling. J Cardiac Surgery 2004;19(5):396-400.

Rarely, major changes in the mitral valve structure will require complete valve replacement rather than repair with a ring. Valve replacement has several disadvantages compared to repair with a ring, including clotting of blood on the artificial valve. This is why ring placement is preferred when possible. Preliminary studies of mitral valve repair in patients with heart failure have been promising but limited.

Surgery to fix the mitral valve in patients with enlarged hearts is controversial. Surgical placement of a ring does improve mitral valve function in most patients, but it is unknown whether this major surgery actually helps patients feel better or live longer. Some experts believe that medical therapy alone without surgery is equally effective without the potential risks of surgery. One of the major concerns about using surgery to treat a leaky mitral valve involves the danger of undergoing open-heart surgery. About 1 in 50 heart failure patients who have open heart surgery die within the first 30 days after surgery.

PROCEDURES

The primary procedure involved in this study is surgical mitral valve repair with placement of a ring around the valve. Half of the patients who agree to be in the study will be randomly chosen to undergo open heart surgery with probable placement of a mitral valve ring at the beginning of the study. The other half of the patients will be asked to delay such surgery for at least 1½ years. If you agree to be in the study you will have a 50% chance of undergoing surgery (similar to a coin toss); you will not know if you will get surgery or not until after you agree to be in the study. All patients will receive the best treatment with medicines and pacemakers, regardless of whether they have surgery or not.

In order to determine whether you have an abnormal mitral valve which qualifies for this study, a transesophageal echocardiogram is required. This procedure involves the placement of an ultrasound probe down the throat and into the stomach to take clear pictures of the heart and the mitral valve.

In order to evaluate whether the surgery is helpful, you will be required to undergo a number of tests at the beginning of the study and then repeat these tests 6 more times (at 1, 3, 6, 12, and 18 months). The tests will involve the following:


Cardiopulmonary exercise stress testing. This involves exercising on a bicycle while being attached to machines which record breathing and heart function.

Chest wall echocardiogram (routine ultrasound of the heart) A blood sample (taking blood from a vein with a needle) collection for biomarkers will be taken for

laboratory evaluations 6-minute walk test Answering routine medical questions Answering questions from the Minnesota Living with Heart Failure Questionnaire This

questionnaire has 21 questions that can indicate impairment in specific areas such as physical impairment (8 questions), social impairment (8 questions) and psychological impairment (5 questions)

Physical examination by a doctor

We want to enroll patients in the study who are willing to receive either surgery or medical therapy alone. You will not be able to choose which therapy you will get.

If you enter the study you will be expected to attend a series of clinic visits over the 1½-year follow-up period. These will take place at:

Initial visit: Screening and Consent (-1 month prior to randomization) Review medical history and medications Sign Informed Consent Form Arrange follow up testing

Preliminary testing at (-1 to 0 months prior to randomization) Transesophageal echocardiogram (TEE) Cardiopulmonary stress test

Study Enrollment0 month: Clinic visit for random assignment to surgery or not,: with baseline testing

A blood sample collection for laboratory evaluations and biomarkers Chest wall echo (TTE) Heart Failure Questionnaire 6 minute walk test

0.5 months: Potential surgery (for 50% of patients)

Follow-up clinic visits after study assignments1 month: Clinic visit for follow-up evaluation

Check up and physical examination Review medical history and medications Heart Failure Questionnaire 6 minute walk test

3 months: Clinic visit for follow-up evaluation Check up and physical examination Review medical history and medications Heart Failure Questionnaire 6 minute walk test

6 months: Clinic visit for follow-up evaluation Check up and physical examination Review medical history and medications Heart Failure Questionnaire 6 minute walk test


A blood sample collection for laboratory evaluations and biomarkers Chest wall echo (TTE) Cardiopulmonary stress test

12 months: Clinic visit for follow-up evaluation Check up and physical examination Review medical history and medications Heart Failure Questionnaire 6 minute walk test A blood sample collection for laboratory evaluations and biomarkers Chest wall echo (TTE) Cardiopulmonary stress test

18 months: Clinic visit for follow-up evaluation Check up and physical examination Review medical history and medications Heart Failure Questionnaire 6 minute walk test A blood sample collection for laboratory evaluations and biomarkers Chest wall echo (TTE) Cardiopulmonary stress test

At the end of the 18 months after random treatment assignment, formal study follow-up will end. Long-term survival status may be collected beyond 18 months using the National Death Index.

Information about your medical history, prior surgeries, current medications, symptoms, and personal habits will be recorded. All data obtained from your evaluations and testing will be kept confidential and protected.

RISKS AND SIDE EFFECTS

While the therapies and tests performed as part of this procedure are all done regularly in the care of heart failure patients, they are associated with significant risks and side effects.

Surgical mitral valve repair: The main potential risk involved with the present study is associated with open heart surgery to repair the mitral valve. Possible side effects include stroke, neuropsychiatric abnormalities (worsened memory and ability to think clearly), myocardial infarction (heart attack), need for repeat surgery for an unsuccessful valve repair, and death. About 1 in 50 heart failure patients who have open heart surgery die within the first 30 days after surgery. Surgery causes the formation of scar tissue, which could slightly increase the risk of bleeding with future heart surgeries (such as heart transplantation). Blood transfusions are not uncommon following heart surgery; blood transfusions carry certain risks, including the possibility of activating the immune system which can then make future heart transplant matching more difficult.

Transesophageal echocardiography: This procedure includes risk involved with the patient being sedated (with drugs) as well as risks from the procedure itself. The main risks are discomfort (gagging), injury to the back of the throat, damage to the esophagus, infection, bleeding, triggering of dangerous rhythms of the heart, choking saliva or vomit into the lungs resulting in pneumonia or difficulty breathing, and death.

Cardiopulmonary exercise testing: Stress testing involves rare but significant risks of heart attack, fast dangerous beating patterns of the heart, stroke or artery clot, and death.


Blood draws: Minimal risk other than discomfort of the needle. About 30 milliliters (2 tablespoons) of blood will be drawn from a vein in your arm on 4 different occasions.

If you experience any of these side effects listed above, the sponsor may need to review your entire medical record.

Women of Childbearing Potential: Pregnancy may worsen heart failure. Additionally, undergoing open heart surgery while pregnant may expose the unborn child to significant risks. Therefore, pregnant women and women who are nursing their babies will be excluded from enrollment into the study. If you are a woman of childbearing potential, a pregnancy test will be done (a blood HCG level), and it must be negative before you can enter this study. If sexually active, you must agree to use appropriate contraceptive measures during the month between enrollment and possible surgery. This usually means two forms of contraception, a hormonal method and a barrier method). If you do become pregnant during this study, you must inform your study physician immediately.

You or your legally authorized representative will be informed in a timely manner if new information becomes available that may affect your willingness to continue participation in this study.

BENEFITS

You may or may not receive any medical benefit from your participation in this study. In the future, other people with a similar condition may benefit from the knowledge obtained from this study.

ALTERNATIVE TREATMENTS

If you choose not to participate in this study, your doctor will discuss alternative treatments with you which may include percutaneous mitral valve repair (surgical procedure done less invasively – without opening the chest).

RIGHT TO WITHDRAW

You may choose not to be in the study, or, if you agree to be in the study, you may withdraw from the study at any time. If you withdraw from the study, no new data about you will be collected for study purposes unless the data concern an adverse event related to the study. If such an adverse event occurs, we may need to review your entire medical record. All data that have already been collected for study purposes, and any new information about an adverse event related to the study, will be sent to the study sponsor.

Your decision not to participate or to withdraw from the study will not involve any penalty or loss of benefits to which you are entitled, and will not affect your access to health care. If you do decide to withdraw, we ask that you contact [INSERT RCC’s PI NAME HERE] in writing and let him or her know that you are withdrawing from the study (contact information below).

INVOLUNTARY WITHDRAWAL

Patients who agree to be in the study will need to undergo (1) transesophageal echocardiogram and (2) cardiopulmonary exercise stress testing prior to randomization. If you are found to have mitral valve disease which is not appropriate for this study (minimal regurgitation or primary abnormality of the mitral valve) or if the exercise capacity is too high, then you will be withdrawn from the study and not randomized to surgery.


COSTS

You will not be charged for tests or visits required by the study. Costs for regular heart failure care (including mitral valve surgery) will be charged to you or your insurance. Tests not conducted under this study will be charged to you or your insurance. You will not be paid for participation in the study. You will receive parking validation or reimbursement for study visits only.

If you do not sign this consent form, you will continue to receive care, but not as a part of this study.

WHAT IF YOU ARE INJURED BY THIS RESEARCH?

You should report any discomforts, problems, or research related injuries immediately to Dr. [INSERT RCC’s PI], the primary investigator for this study, at [xxx xxx-xxxx]. Immediate necessary medical care is available at [INSERT RCC INSTITUTION] in the event that you become sick or injured as a result of your participation in this research study. However, there is no commitment by [INSERT RCC INSTITUTION] physicians to provide monetary compensation or free medical care to you in the event of a study-related injury. Further information concerning this and your rights as a research subject can be obtained from the [INSERT RCC INSTITUTION’S] Institutional Review Board at [xxx-xxx-xxxx].

CONFIDENTIALITY AND PROTECTION OF RESEARCH SUBJECTS' IDENTITY

Study records that identify you will be kept confidential, as required by law. Federal Privacy Regulations provide safeguards for privacy, security, and authorized access. Your records will not be identified by name, social security number, address, telephone number, or any other direct personal identifier in study records disclosed outside of your hospital. For records disclosed outside of your hospital, you will be assigned a unique code number. The key to the code will be kept at the study site, [INSERT RCC’s Institution NAME HERE]. As part of the study, results of your study-related laboratory tests will be reported to the data coordinating center, the Duke Clinical Research Institute (DCRI).

Your records may be reviewed in order to meet federal or state regulations. Reviewers may include representatives from the National Institutes of Health, representatives from your hospital’s Institutional Review Board, and Duke Clinical Research Institute associates. If your research record is reviewed by any of these groups, they may also need to review your entire medical record.

By signing this consent, you are authorizing use of your test results for further laboratory evaluations and research.

The Data Coordinating Center (DCC), Duke Clinical Research Institute, which oversees all Heart Failure Network clinical trials, including this one, has obtained a Certificate of Confidentiality to further protect research information from forced disclosure. Avoiding 'forced disclosure' means that the doctors, researchers, and other staff involved with this medical research study can not be forced to provide any subjects' identities in any Federal, State or local, civil, criminal, administrative, legislative or other legal proceeding, by subpoena or other means. This Certificate of Confidentiality was issued to the DCC by the National Institutes of Health, a government agency.

EXPIRATION DATE OR EVENT FOR RECORD RETENTION

This consent/authorization will be retained for at least six years from the date it was last in effect.

Your study records will be retained in your research record for a minimum of two years after the study is concluded. At that time, one of two things will occur: either the research information not already in your


medical record will be destroyed or information identifying you will be removed from all study results. Any research information in your medical record will be kept indefinitely.

Your research information could be disclosed by someone who received it from us. If this happens, the information may no longer be covered by the federal privacy regulations.

Information that could identify you by name will not be used if the results of this study are published.

QUESTIONS

If you have any questions about this study, you can contact:[INSERT RCC’s PI NAME HERE]PI ADDRESSPI PHONE

If you have questions regarding your rights as a participant in this study, you can contact:[INSERT RCC’s IRB CONTACT NAME HERE]IRB ADDRESSIRB PHONE


STATEMENT OF CONSENT

"The purpose of this study, procedures to be followed, risks and benefits have been explained to me. I have been allowed to ask the questions I have, and my questions have been answered to my satisfaction. I have been told whom to contact if I have additional questions. I have read this consent form and agree to be in this study, with the understanding that I may withdraw at any time without affecting my future medical care. I have been told that I will be given a signed copy of this consent form."

___________________________________Name of Subject

___________________________________ ____________Signature of Subject Date

___________________________________Name of Legally Authorized Representative(if applicable)

___________________________________ ____________ Signature of Legally Authorized Representative Date(if applicable)

___________________________________Relationship of Legally Authorized Representative to Subject(if applicable)

_________________________________Name of Person Obtaining Consent

___________________________________ ____________Signature of Person Obtaining Consent Date

_________________________________Name of Witness(if applicable)

___________________________________ ____________Signature of Witness (if applicable) Date


Documents

Appendix C: Informed Consent Form