Download Poseidon Informed Consent

eProst ID: 20090352
Version: 0.01
Approved
Approval Date: 9/21/2009
Exp. Date: 9/13/2010
Consent to Participate in a Clinical Research Study
Title of Study: A Phase I/II Randomized Pilot Study of the Comparative Safety and
Efficacy of Transendocardial Injection of Autologous Mesenchymal Stem Cells
Versus Allogeneic Mesenchymal Stem Cells in Patients With Chronic Ischemic Left
Ventricular Dysfunction Secondary to Myocardial Infarction.
The PercutaneOus StEm Cell Injection Delivery Effects On Neomyogenesis Pilot Study
(The POSEIDON-Pilot Study)
Principal Investigator: Joshua M. Hare, MD
Department: Department of Medicine, Division of Cardiology & Interdisciplinary Stem
Cell Institute
Phone Numbers: 305-243-1999 (24 hour access)
Email Address: [email protected]
Co-Investigators: Alan W. Heldman, MD; Juan Zambrano, MD; Si Pham, MD; Joel
Fishman, MD; Pradip Pattany, PhD; Ian McNiece, PhD; & Rick
Schwarz, PhD
Department: Department of Medicine, Division of Cardiology
Phone Numbers: 305-243-5138 / 305-243-5554
Email Address: [email protected]
READ THE FOLLOWING CAREFULLY
This consent form contains important information, so that you can decide if you wish to
take part in this study. If you have any questions that remain unanswered, please ask
the Study Doctor, or one of his research study personnel, before signing this form.
NAME: _________________________________
MRN: __________________________________
AGE: ___________ DOB: _____/_____/______
PAGE 1 OF 25
eProst ID: 20090352
Version: 0.01
Approved
Approval Date: 9/21/2009
Exp. Date: 9/13/2010
You are being asked to give permission to participate in a research study. Before you
give your consent (permission) to be part of this study, please read the following
information and ask as many questions as necessary to be sure that you understand
what your participation will involve.
PURPOSE
Heart failure is a serious and common condition. It is a condition in which the heart
muscle does not pump blood throughout the body as well as it should. Over a period of
years, the heart’s pumping ability continues to get worse and a heart transplant may
become necessary. Treatment options are extremely limited. Also, because of the small
number of donor organs, very few people receive heart transplants when they need
one.
Stem cells are cells that do not yet have a specific function in the body. Stem cells are
produced by the bone marrow (the spongy tissue inside of your bones). Human
mesenchymal stem cells (hMSCs) are a type of stem cell that can be grown from
human bone marrow. Stem cells can develop into other types of more mature cells,
such as blood and muscle cells. It is hoped that by placing these cells in the heart, they
can give rise to new muscle that will allow the heart to work better. This research study
is being conducted to determine whether giving human mesenchymal stem cells
(hMSCs) to patients with heart muscle damage is safe. We will also examine whether
this treatment improves heart function.
The hMSCs given to you in this study will either be taken from your bone marrow, or
taken from a human donor’s bone marrow. The procedure for getting the stem cells is
explained below. Giving patients their own hMSCs (autologous hMSCs) or a human
donor’s bone marrow hMSCs (allogeneic hMSCs) is an investigational procedure that
has been authorized by the Food and Drug Administration (FDA) for this study.
Previous studies in the United States, and around the world, have tested human adult
stem cell therapy as a potential treatment for patients with heart disease. Data from
these studies indicate that this method is safe. Also, some patients have shown signs of
improved heart function.
You are being asked to be in this research study because you have chronic heart failure
that resulted from a past heart attack. To be in this study, you must be able to walk for a
short period of time.
NAME: _________________________________
MRN: __________________________________
AGE: ___________ DOB: _____/_____/______
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eProst ID: 20090352
Version: 0.01
Approved
Approval Date: 9/21/2009
Exp. Date: 9/13/2010
You cannot be in this study if you:

Have poor kidney function. This will be determined by blood tests.

Have a known, serious radiographic contrast (x-ray dye) allergy with symptoms
such as breathing problems, low blood pressure, heart problems, or any reaction
to contrast in the past that required hospitalization.

Have an abnormal blood count with no known medical explanation.

Have a liver that is not working properly. This will be determined by blood tests.

Have a problem with your blood clotting that is not due to medication that you are
taking (i.e., Coumadin therapy).

Have known allergies to penicillin or streptomycin.

Have a history of aortic stenosis or insufficiency (heart valve disease).

Have had firing of your implantable defibrillator in the past 60 days.

Have an implanted prosthetic aortic valve or a heart constrictive device.

Need a cardiac catheterization to open up a blood vessel(s) in your heart. If you
require and are able to undergo a cardiac catheterization procedure you should
do so at least 3 months before enrolling in this study.

Have life-threatening arrhythmia (abnormal heart rate).

Have a history of advanced 2nd or 3rd degree heart block and are without a
pacemaker.

Have undergone an organ transplant.

Have a history of cancer within the past 5 years, except certain skin and cervical
cancers.

Have a life-threatening condition other than your heart condition that limits your
lifespan to less than 1 year.

Have a history of drug use or alcohol abuse within the past 24 months.

Are on medication to suppress your immune system, such as corticosteroids or
TNFα antagonists. If you are taking medications prescribed to you by a doctor,
NAME: _________________________________
MRN: __________________________________
AGE: ___________ DOB: _____/_____/______
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eProst ID: 20090352
Version: 0.01
Approved
Approval Date: 9/21/2009
Exp. Date: 9/13/2010
the study doctor will be able to tell you whether the medications you are taking
fall into either of these two classes of drugs.

Test positive for HIV, hepatitis B or hepatitis C infection.

Are currently participating (or participated within the previous 30 days) in another
research study.

Are a female patient who is pregnant, nursing, or of childbearing potential and
not taking birth control.

Are unable to lie flat for at least 30 minutes.

Have a history of asthma or chronic obstructive pulmonary disease.
NUMBER OF STUDY PARTICIPANTS
This is a pilot (preliminary) safety study. This study will test the safety of giving different
doses of autologous (from you) and allogeneic (from a donor) hMSCs. A total of 30
people will participate in this study. Half of the participants will get autologous hMSCs.
Half of the participants will get allogeneic hMSCs. This study is being performed at the
University of Miami, Miller School of Medicine and The Johns Hopkins Hospital.
DURATION OF STUDY
The total length of your participation in this study will be 13 months, including follow-up
visits. If you agree to participate in this study you will spend a minimum of 4 days in the
hospital. After you leave the hospital, you will need to come back in two weeks to be
examined by the study team. You will then come back one day per month for the next 6
months to be examined by the Study Team. Most of these monthly visits will take less
than an hour. However, the month 3, 6 and 12 visits may last between 4 and 6 hours
because you will have additional tests at that time. The final visit will be 13 months after
the start of your participation in this study.
You will be asked to have separate blood and bone marrow samples taken for genetic
testing. If you agree, we will request that you sign a separate genetic research consent
form. These blood and bone marrow specimens will be identified so they can be linked
NAME: _________________________________
MRN: __________________________________
AGE: ___________ DOB: _____/_____/______
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eProst ID: 20090352
Version: 0.01
Approved
Approval Date: 9/21/2009
Exp. Date: 9/13/2010
to you. They may also be stored indefinitely. You do not have to participate in the
genetic portion of this research to take part in the main study.
PROCEDURES
Summary of Procedures (A detailed description of the procedures follows this table)
Study Interval
Procedures to be Performed
Screening Phase
o Sign Informed Consent
Form
o History and Physical
o Vital Signs
o 12-Lead ECG
o 48-Hour Ambulatory ECG
o Echocardiogram
o Concomitant Medications
Evaluation
BASELINE VISIT #1
Baseline Phase
Timing of bone marrow aspiration will
depend on which Treatment Group you
are randomized to during this visit.
If Group A (Autologous): The bone
marrow aspiration will take place 4-6
weeks before your catheterization (see
Day 1 below).
If Group B: Allogeneic hMSCs will be
prepared for infusion by the University of
Miami 4-6 hours before your
catheterization (see Day 1 below).
Day 1 (Catheterization Day)
The actual date will depend on whether
you are randomized to Treatment Group
A (1A or 2A or 3A) or Treatment Group B
(1B or 2B or 3B) (see Day 1 below).
o HIV and Hepatitis Blood
Tests
o Blood and Urine Tests
o CT Scan of Chest,
Abdomen, and Pelvis
BASELINE VISIT #2
o
o
o
o
o
o
History and Physical
Vital Signs **
Randomization
Bone Marrow Aspiration *
Biomarker Test (Group A)
Concomitant Medications
Evaluation
o CT Scan of Heart
* Bone Marrow Aspiration will
occur for those patients
randomized to Group A (1A or
2A or 3A).
** All procedures listed above
will occur within 14 days of the
final screening exam
o
o
o
o
o
o History and Physical
o Catheterization
o Investigational Agent (stem
cell injection)
o Post-Procedural Care
o Biomarker Test (Group B)
o Serum or Urine Pregnancy
Test
o Concomitant Medications
Evaluation
o Vital Signs
o 12-Lead ECG
o 48-Hour Ambulatory ECG
o Echocardiogram **
o Adverse Event Assessment
o Blood and Urine Tests
** Echocardiogram will be
performed immediately postcatheterization and 4-6 hours
post catheterization
Treadmill to Assess VO2 **
Six-Minute Walk Test **
Pulmonary FEV1 **
MLHF Questionnaire **
NYHA Functional Class
Assessment
** All procedures listed above
will occur within 14 days of the
final screening exam
NAME: _________________________________
MRN: __________________________________
AGE: ___________ DOB: _____/_____/______
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eProst ID: 20090352
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Approved
Study Interval
Days 2, 3, & 4
You will remain in the hospital for
days 2 through 4.
Approval Date: 9/21/2009
Exp. Date: 9/13/2010
Procedures to be Performed
o Post-Procedural Care
o 12-Lead ECG
o Vital Signs
o Blood and Urine Tests
o Adverse Event Assessment
o Concomitant Medications
Evaluation
o
o
o
o
Echocardiogram (Day 2)
48- Hour Ambulatory ECG
Pulmonary FEV1(Day 4)
Serum Troponin & CK-MB
Test (Day 2)
Day 14
o
o
o
o
Months 1, 2, 3, 4, & 5
o
o
o
o
o
o
History and Physical
12-Lead ECG
Vital Signs
Blood and Urine Tests
Adverse Event Assessment
Pulmonary FEV1 (Months 2
& 4 only)
o Concomitant Medications
Evaluation
o
o
o
o
o
48-Hour Ambulatory ECG
Echocardiogram (Month 3)
NYHA Functional Class
MLHF Questionnaire
Serum or Urine Pregnancy
Test
Month 6
o
o
o
o
o
o
o
o
o
History and Physical
Vital Signs
12-Lead ECG
Pulmonary FEV1
Treadmill to Assess VO2
Six-Minute Walk Test
Echocardiogram
MLHF Questionnaire
Concomitant Medications
Evaluation
o
o
o
o
o
o
Blood and Urine Tests
Biomarker Test
48-Hour Ambulatory ECG
NYHA Functional Class
Adverse Event Assessment
Serum or Urine Pregnancy
Test
Month 12
o
o
o
o
o
History and Physical
Vital Signs
Blood and Urine Tests
12-Lead ECG
Pulmonary FEV1
o Concomitant Medications
Evaluation
o CT Scan of Heart, Chest,
Abdomen, and Pelvis
o
o
o
o
o
o
o
Echocardiogram
48-Hour Ambulatory ECG
Treadmill to Assess VO2
Six-Minute Walk Test
NYHA Functional Class
MLHF Questionnaire
Adverse Event Assessment
Month 13
History and Physical
Vital Signs
12-Lead ECG
Adverse Event Assessment
o Concomitant Medications
Evaluation
o Pulmonary FEV1
o 48-Hour Ambulatory ECG
NAME: _________________________________
MRN: __________________________________
AGE: ___________ DOB: _____/_____/______
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eProst ID: 20090352
Version: 0.01
Approved
Approval Date: 9/21/2009
Exp. Date: 9/13/2010
If you agree to be in this study, we will ask you to do the following things:
Screening Phase
First, we will do a screening evaluation. The purpose of the screening evaluation is to
find out if you are eligible to be in the study. At this visit, we will do a physical
examination and take vital signs (temperature, pulse and blood pressure). We will ask
about your medical history, including your past and present illnesses. You will need to
tell us about all medicines you are currently taking and discuss any current alcohol or
drug use. If you currently abuse drugs or alcohol, you will not be eligible to be in this
study.
On the day of your Screening appointment, we will draw a blood sample from a vein in
your arm (about 2 Tablespoons) for testing in the laboratory. We may ask you to not eat
or drink anything for 8 hours prior to the blood test. The tests will measure certain
chemicals (electrolytes) and count your blood cells. The Study Team will also request a
urine sample.
We will also be testing to see if you are infected with the HIV (the virus that causes
AIDS) and/or hepatitis (liver) viruses. For the HIV testing, we will ask you to sign a
separate consent form. If you are infected with HIV or have active hepatitis, you will not
be eligible to be in this study.
If you are a female of childbearing potential, we will do a pregnancy test (a blood test). If
you are pregnant, you will not be eligible to be in this study.
We will obtain the blood for all of these tests through a single needle puncture of a vein.
The blood will be drawn by a trained person.
You will have some tests of your heart function at this screening visit. First, we will do a
12-Lead electrocardiogram (ECG). In order to do this test, a trained expert will apply
pads to certain areas of your body. The ECG will provide a picture of the electrical
workings of the heart. It takes about 5 minutes to complete.
NAME: _________________________________
MRN: __________________________________
AGE: ___________ DOB: _____/_____/______
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eProst ID: 20090352
Version: 0.01
Approved
Approval Date: 9/21/2009
Exp. Date: 9/13/2010
You will also be asked to wear a 48-Hour Ambulatory ECG called a Holter monitor. The
Holter monitor is a machine that continuously records your heart's rhythms. The monitor
will be worn for 2 days during normal activity. You can go home with the monitor and do
not need to stay at the hospital. Electrodes (small conducting patches) will be applied
onto your chest and attached to a small recording device. You can carry the Holter
monitor in a pocket or in a small pouch worn around your neck or waist. You will receive
a diary (notebook) to write down any symptoms you experience while wearing the
device.
If you have a recorded episode of ventricular tachycardia (an irregular heart beat) on the
12-Lead ECG, or the 48-Hour Ambulatory ECG during this screening phase testing, you
will be removed from the study.
The Study Team will also complete an echocardiogram of your heart. This test will look
at how well your heart is pumping blood with each heartbeat. During this procedure, a
trained professional (a sonographer) will move a microphone-like object (a hand-held
device that sends and receives ultrasound signals) over your chest area. A small
amount of gel used on the end of the transducer helps it glide over the skin. The
transducer sends out high-frequency sound waves that are shown on a video screen
and saved to a computer.
A CT scan of your heart, chest, abdomen and pelvis will be performed. This test uses xrays and computers to produce images of your body. To increase the quality of these
pictures, an x-ray dye will be given by injection into a vein and by mouth prior to the CT
scan. An expert technologist will help you lie in the correct position on the examining
table. The table will then automatically move into place for imaging. It is very important
that you lie as still as possible during the procedure. You might be asked to hold your
breath briefly at intervals when the X-ray images are taken. The entire procedure should
be less than an hour.
This visit may take place over more than one day.
Baseline Phase
After all screening exams are completed and it has been determined that you are still
eligible for the study, you will be enrolled on the study. You will be randomized to either
Group 1A or 2A or 3A to receive autologous hMSCs or Group 1B or 2B or 3B to receive
allogeneic hMSCs. Randomization means that you are put into a group by chance,
NAME: _________________________________
MRN: __________________________________
AGE: ___________ DOB: _____/_____/______
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eProst ID: 20090352
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Approval Date: 9/21/2009
Exp. Date: 9/13/2010
similar to the flip of a coin. A computer program will place you in one of the study
groups. Neither you nor your doctor can choose the group you will be in.
Group 1 A: Five (5) participants will be treated with
20 million Autologous hMSCs given in total volume
of 0.5 milliliter.
These participants will not be treated less than 5
days apart and will each undergo full evaluation for
5 days to demonstrate there are no adverse events
prior to proceeding with Group 2.A
Group 2 A: Five (5) participants will be treated with
100 million Autologous hMSCs given in total
volume of 2.5 milliliter.
Group 1 B: Five (5) participants will be treated with
20 million Allogeneic hMSCs given in total volume
of 0.5 milliliter.
These participants will not be treated less than 5
days apart and will each undergo full evaluation for
5 days to demonstrate there are no adverse events
prior to proceeding with Group 2 B.
Group 2 B: Five (5) participants will be treated with
100 million Allogeneic hMSCs given in total volume
of 2.5 milliliter.
These participants will not be treated less than 5
days apart and will each undergo full evaluation for
5 days to demonstrate there are no adverse events
prior to proceeding with Group 3 A.
Group 3A: Five (5) participants will be treated with
200 million Autologous hMSCs given in total
volume of 5 milliliter.
These participants will not be treated less than 5
days apart and will each undergo full evaluation for
5 days to demonstrate there are no adverse events
prior to proceeding with Group 3 B.
These participants will each undergo full evaluation
for 5 days to demonstrate there are no adverse
events.
These participants will each undergo full evaluation
for 5 days to demonstrate there are no adverse
events.
Group 3B: Five (5) participants will be treated with
200 Allogeneic hMSCs given in total volume of 5
milliliter.
Baseline Visit #1 will take place following confirmation that you are still eligible for the
study. If you are randomized to Group 1A or 2A or 3A (autologous hMSCs) you will
have your bone marrow aspiration procedure during this visit. Your catheterization
procedure to receive hMSCs will be scheduled 4-6 weeks after the successful bone
marrow aspiration. Patients whose bone marrow aspirate fails to grow hMSCs will be
removed from the study.
Bone Marrow Aspiration: For this procedure one of the study doctors will
take bone marrow from your hip bone. You will receive medication, in your
NAME: _________________________________
MRN: __________________________________
AGE: ___________ DOB: _____/_____/______
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eProst ID: 20090352
Version: 0.01
Approved
Approval Date: 9/21/2009
Exp. Date: 9/13/2010
vein, to help with the pain and discomfort. The type of anesthesia (pain
medication) will be decided by the clinical research study team. At the
hospital you will be asked to sign another consent form for the anesthesia.
Usually the bone marrow aspiration will be done under a protocol of
"conscious sedation" where you will receive intravenous Fentanyl or
Demerol and Versed. This type of sedation induces an altered state of
consciousness that minimizes pain and discomfort. Patients who receive
conscious sedation usually are able to speak and respond to verbal cues
throughout the procedure, communicating any discomfort they experience
to the attending nurse and doctor. A nurse and a doctor will monitor your
heart rate and rhythm during the procedure. You will lie on your side to
enable the physician to have optimal access to your hip area. This area
will be cleaned with a germ-killing cleanser followed by the application of
numbing medicine (local anesthesia) for bone marrow aspiration. Next,
the study doctor will insert a special needle into your hip bone. The needle
has a tube attached to it, which creates suction. A small sample of bone
marrow fluid flows into the tube. The average amount of aspirate will be 50
ml (a little more than 3 tablespoons) with an expected range of 30 ml to 60
ml. The needle is removed. You may feel a small prick and a slight
burning sensation with the local anesthetic. Pressure is felt as the needle
is inserted into your body and when the aspiration is performed. More than
one aspiration will be performed to obtain enough stem cells. Up to 4
aspirations (separate needle punctures) may be necessary to collect your
bone marrow. When the procedure is over, a pressure dressing with
antibiotic ointment will be applied and will stay on for approximately 24
hours.
If you are randomized to Group 1B or 2B or 3B (allogeneic hMSCs), the hMSCs will be
prepared for infusion by the University of Miami approximately 4-6 hours prior to the
scheduled catheterization procedure on Day 1.
During the Baseline Visit #2 all patients will undergo additional testing to gather baseline
data. The Baseline Phase will take place within 14 days of the final screening exam.
NAME: _________________________________
MRN: __________________________________
AGE: ___________ DOB: _____/_____/______
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eProst ID: 20090352
Version: 0.01
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Approval Date: 9/21/2009
Exp. Date: 9/13/2010
You will have a number of additional tests and procedures completed during this
Baseline #2 visit, including:
A Treadmill Exam to Measure your Peak VO2 will be performed. This test shows the
maximum amount of oxygen your heart can provide to your muscles during activity. For
this procedure, you will first be asked to blow into a tube connected to a machine. Then
you will have small adhesive (sticky) electrodes put on your chest and sides. The wires
attached to these electrodes will connect you to a heart monitor. You will then start
walking until one of two things happen: Either you simply cannot go on and must stop,
or the Study Doctor will end the test when he/she has the information needed. The time
it takes to complete this test varies. It is usually less than an hour from start to finish.
A Six-Minute Walk Test will be performed. This test is performed by having you walk
for six minutes. During the test you will be allowed to stop and rest as often as desired,
but you may be encouraged to continue walking. After six minutes, the total distance
walked is measured and recorded.
A Pulmonary function test (FEVI) will be performed. You will have a lung test called
an FEV1. This is a test that measures the amount of air that you can blow in one
second when you blow out as hard as you can.
You will complete a MLHF Questionnaire. The MLHF (Minnesota Living with Heart
Failure) Questionnaire is a 21 item self-administered questionnaire. You will be asked to
complete this short survey during the Baseline visit and several additional times during
the study. Although the Study Team would like you to complete the entire form, you may
choose not to answer a question for whatever reason. The Study Team will use the
results to assess how your heart failure symptoms affect your quality of life.
Lastly, the Study Doctor will determine your New York Heart Association (NYHA)
Functional Classification. This is a simple way of classifying the extent of your heart
failure. This evaluation places you in one of four categories based on your physical
activity abilities.
Day 1
On Day 1 you will be admitted to the hospital for a cardiac catherization and injection of
the investigational agent (stem cells) into your heart. The stem cells will be either
NAME: _________________________________
MRN: __________________________________
AGE: ___________ DOB: _____/_____/______
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autologous hMSCs or allogeneic hMSCs. You will be requested to not eat or drink
anything for at least 8 hours prior to the catheterization.
During the procedure, a very small catheter (hollow tube) will be advanced from an
artery in your groin through the aorta into the heart. Once the catheter is in place, the
Study Doctor will use a device made by BioCardia Incorporated called a Helical Infusion
Catheter to inject your heart 10 times with stem cells. The entire process will take about
3 hours. The Study Doctor and other trained technicians and nurses will carry out the
procedure in a Cardiac Catheter Laboratory.
You will be awake and able to follow instructions during the catheterization. However, a
mild sedative will be given before the procedure to help you relax.
You may feel some discomfort at the site where the catheter is inserted. Local
anesthesia will be used to numb the site, so the only sensation should be pressure. You
may experience some discomfort from having to remain still for a long time.
After the procedure, the catheter is removed. You might feel a firm pressure at the
insertion site. This is done to prevent bleeding. You will also need to lie flat on your back
for a few hours after the test to avoid bleeding. This may cause some mild discomfort.
The Study Team and hospital staff will take your vital signs frequently for a couple of
hours after the procedure. You will also have an echocardiogram immediately following
the procedure and again 4-6 hours later. The echocardiogram will evaluate how well
your heart is pumping blood with each heartbeat (as described above in the Screening
Phase section).
You will also have blood and urine samples taken as well as a 12-Lead ECG performed
and a 48-Hour Ambulatory ECG (Holter monitor) applied.
You will need to remain in the hospital for the next four days. During this time the Study
Team and hospital staff will monitor your vital signs, the catheterization site, and watch
you closely for any adverse events (side effects).
NAME: _________________________________
MRN: __________________________________
AGE: ___________ DOB: _____/_____/______
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Days 2-4
Each day you are in the hospital, you will also have a 12-Lead ECG to look at your heart
rhythm and be required to wear a 48-Hour Ambulatory ECG (Holter monitor) The
monitor will continuously record your heart's rhythm. These are the same tests that
were completed for the Baseline Phase described above.
Additionally, blood and urine samples will be requested. These samples will look at the
composition of your blood and urine and help the Study Doctor monitor your safety.
You will be discharged (allowed to go home) from the hospital on day 4 unless you are
experiencing any bad reactions to the treatment, and the Study Doctor believes you
should remain hospitalized longer. Before being discharged you will repeat the
Pulmonary FEV1 (lung function) test that was also performed during the Baseline
Phase. Once discharged, you will be asked to visit the Study Team in 2 weeks (14
days) and then one day per month for the next six (6) months.
Day 14
You will need to see the Study Team 2 weeks (+ 3 days) following your catheterization
to review any adverse events (side effects) you may be experiencing. You will also have
the following tests/assessments:




Vital Signs
12-Lead EKG
48-Hour Ambulatory ECG (Holter monitor)
Pulmonary FEVI (lung function test)
Months 1- 6
One day each month for the next six (6) months you will need to see the Study Team to
review any adverse events (side effects) and have the following tests/assessments:




History, Physical, and Vital Signs
12-Lead ECG
Blood and Urine Samples
48-Hour Ambulatory ECG (Holter monitor)
NAME: _________________________________
MRN: __________________________________
AGE: ___________ DOB: _____/_____/______
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
Approval Date: 9/21/2009
Exp. Date: 9/13/2010
MLHF Questionnaire
The Study Doctor will also determine your NYHA Functional Class
Month 2 Additional Test: During your month 2 visit you will have a Pulmonary FEV1
(lung function) test. This is the same test that was done during previous visits.
Month 3 Additional Tests: During your month 3 visit you will have an
echocardiogram. These are the same tests as were done during previous visits.
Your month 3 visit should last about 4 hours.
Month 4 Additional Test: During your month 4 visit you will have a Pulmonary FEV1
(lung function) test. This is the same test that was done during previous visits.
Month 6 Additional Tests: During your month 6 visit you will have an
echocardiogram. These are the same tests as were done during previous visits. The
Study Team will also request that you perform the treadmill exam to determine your
Peak VO2, a six-minute walk test and a pulmonary FEV1 (lung function) test during
this visit. Finally, the Study Team will take a sample of your blood and bone marrow
during this visit if you previously agreed to the genetic test. The total time for your
month 6 visit will be about 6 hours.
Month 12
You will be requested to return for a visit about 12 months after you began this study.
During this month 12 visit you will have:
 History, Physical, and Vital Signs
 Echocardiogram
 12-Lead ECG
 Pulmonary FEV1 (lung function test)
 Treadmill exam to measure Peak VO2
 Six-minute walk test
 48-Hour Ambulatory ECG (Holter monitor)
 Blood and Urine Samples
 MLHF Questionnaire
 The Study Doctor will also determine your NYHA Functional Class
 The Study Team will evaluate you for any adverse events
This visit should take about 6 hours.
NAME: _________________________________
MRN: __________________________________
AGE: ___________ DOB: _____/_____/______
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Month 13 (final visit)

CT scan of your heart, chest, abdomen, and pelvis
Specimens
Most of the collected specimens described above will be destroyed at the completion of
the study. The only exception is if you agreed to the genetic testing of your blood and
bone marrow. These samples may be retained indefinitely.
RISKS AND DISCOMFORTS
Cardiac Catherization
There may be slight discomfort in your groin during the insertion of the catheter into the
artery. Occasionally, a small accumulation of blood (hematoma) may form at the point of
insertion of the catheter. This may result in a small lump that will disappear.
Occasionally, a small amount of bleeding may occur around the catheter site. On rare
occasions, a local infection may occur around the catheter site. Other complications of
the arterial catheter occur very rarely and are usually seen only when the catheter
remains in the artery for extended periods of time. These complications may include
obstruction (blockage) of the artery and a decrease in the circulation of the leg.
The cardiac catheterization will expose you to some radiation. To give you an idea
about how much radiation you will get, we will make a comparison with an every-day
situation. Everyone receives a small amount of unavoidable radiation each year. Some
of this radiation comes from space and some from naturally-occurring radioactive forms
of water and minerals. This cardiac catheterization portion of the research study gives
your body the equivalent of about 1 extra year’s worth of this natural radiation.
Investigational Human Cell Injections into the Heart
If you are randomized to the investigational treatment in Group 1A or 2A or 3A you will
receive your own mesenchymal stem cells taken from your hip (autologous hMSCs). If
you are randomized to the investigational treatment in Group 1B or 2B or 3B you will
receive mesenchymal stem cells manufactured by the University of Miami (allogeneic
hMSCs). These investigational cells will be injected directly into your heart via an artery
in the right groin with an investigational catheter made by BioCardia (Helical Infusion
NAME: _________________________________
MRN: __________________________________
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Catheter). Previous animal and human studies in which mesenchymal stem cells were
injected into the heart have reported few complications.
However, there are possible risks of this procedure. Although extremely rare, these
risks include: ventricular and/or atrial arrhythmias (abnormal heart rhythms), myocardial
infarction (heart attack), fluid build-up around the heart, heart perforation, abnormal
tissue formation, and stroke. Death may also occur.
There may be other risks or side effects of this investigational treatment that are not yet
known. You will be informed of new findings during the study. You will be required to
stay in the hospital for a minimum of 4 days after the injections so the Study Doctor and
his staff can monitor your safety.
If you happen to receive allogeneic mesenchymal cells, it is possible that your body
might react and reject the cell therapy treatment. Human clinical research studies with
allogeneic mesenchymal cells in heart patients have provided evidence against
rejection due to graft versus host disease (GVHD, where functional immune cells in the
transplanted marrow recognize the recipient as "foreign" and mount an immunologic
attack).
Bone Marrow Aspiration
The risks associated with the bone marrow aspiration are small. The amount of pain
and discomfort will depend on your pain tolerance, which differs from person to person.
Some patients describe a sharp pain, others say it feels like a long hard punch or kick.
This usually lasts for 1-5 minutes starting during the actual procedure. Tenderness over
the area may last for a few days. Bleeding from the site or infection may occur but is
rare. The procedure will be performed by an experienced physician under conscious
sedation. Only participants in Group 1A, 2A, or 3A (autologous MSCs) will have bone
marrow collected.
Possible Risks with Anesthetics
The risks associated with the use of the anesthetics Fentanyl or Demerol and Versed
for conscious sedation include a brief period of amnesia after the procedure, headache,
nausea and vomiting or unpleasant memories of the procedure. These medications
have the potential to decrease your breathing and decrease your blood pressure
temporarily. Your blood pressure and level of oxygen in your blood will be monitored
during the procedure and if either decreases significantly you will receive treatment until
NAME: _________________________________
MRN: __________________________________
AGE: ___________ DOB: _____/_____/______
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they return to a satisfactory level. The study team will look for any allergic reactions you
may experience that are caused by the anesthetic.
Needle Insertion for Blood Drawing
The risks of blood drawing include: fainting, the occurrence of temporary discomfort
and/or bruise at the site of puncture; rarely, infection or the formation of a small clot or
swelling to the vein and surrounding area may occur.
CT scan
If you take part in this research, you will have several medical imaging studies that use
radiation. You will have two CT scans of your heart, chest, abdomen, and pelvis. CT
images are made possible through the use of radiation. The amount of radiation
exposure you will receive from undergoing your CT scans is about 4.2 rems in the first
year, 4.2 rems at the beginning of the second year and you will receive about 1.0 rem
during the injection of stem cells into the heart. Naturally occurring radiation (cosmic
radiation, radon, etc.) produces whole body radiation exposures of about 0.3 rems per
year. Occupationally exposed individuals (people who work around or with radiation) are
permitted to receive whole body exposures of 5 rems per year.
In addition, CT scans are performed during the injection of CT contrast (dye).
Reactions to the contrast agent are uncommon and occur in less than 1 in 1000 people.
These reactions can range from mild itching and hives, to serious reactions including
difficulty breathing and anaphylactic shock (low blood pressure and severe problems
with breathing). Anaphylactic shock can result in death. To minimize this risk, you will
not be allowed to join this study if you have a known allergy to CT contrast. In the event
you have an allergic reaction to CT contrast, a physician will be present to give you
medical treatment. There is also a small risk of kidney damage from the contrast agent.
Such damage is also rare and is usually, but not always, reversible. You will not be
allowed to have a CT with contrast if your kidney function is impaired.
In order to measure the blood flow in your heart you will receive an infusion of
adenosine, a commonly prescribed stress testing medication. Adenosine is a very short
acting drug and most of the side effects go away within 1-2 minutes after the infusion is
turned off. The side effects include flushing (44%), chest discomfort (40%), urge to
breathe deeply (28%), headache (18%), throat, neck or jaw discomfort (15%),
gastrointestinal discomfort (13%), and lightheadedness or dizziness (12%). Less
common side effects include arm or hand discomfort (4%), temporary ECG
abnormalities (3%), tingling of the limbs, hands and feet (2%), low blood pressure (2%),
NAME: _________________________________
MRN: __________________________________
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and nervousness (2%). Heart attacks, life-threatening abnormal heart rhythms and
death have been reported in very rare instances (<1%).
Echocardiogram
An echocardiogram is painless. The gel that is applied by a technician may feel cool.
There may be a sensation of pressure from the transducer (microphone-like device)
being placed on your chest in order to obtain an enhanced picture.
12-Lead ECG
Although there is no pain involved with the ECG procedure, the adhesive used to keep
the electrodes in place during the ECG may irritate your skin and cause redness.
48-hour ambulatory ECG
For this test you will wear a monitor and have electrodes (small conducting patches)
applied to your chest. Although painless, you will need to carry the monitor in a pocket
or in a small pouch worn around your neck or waist.
Treadmill determination of Peak VO2
You will be breathing for a while through your mouth and into a tube during this test.
You will also be walking on a treadmill. Some discomforts you may experience during
the test include: difficulty swallowing because you are breathing through your mouth, a
faster heart rate, and shortness of breath (difficulty breathing). A couple of common
discomforts after the exam are a dry throat and fatigue (tiredness).
Six minute walk test
During the six-minute walk test, you may develop shortness of breath (difficulty
breathing), your heart may go faster than usual, the level of oxygen in your blood may
decrease, and/or you may develop pain or soreness in your legs. You can choose to
stop at any time during the test.
Pulmonary Function (FEV1)
Since the test involves some forced breathing and rapid breathing, you may have some
temporary shortness of breath or lightheadedness. You breathe through a tight-fitting
mouthpiece, and you'll have nose clips. The risk is minimal for most people. There is a
small risk of collapsed lung in people with a certain type of lung disease.
NAME: _________________________________
MRN: __________________________________
AGE: ___________ DOB: _____/_____/______
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Pregnancy
This clinical research may involve unknown risks to unborn children; therefore, you must
practice medically accepted methods of birth control while you are on this study.
Acceptable methods of birth control include: birth control pills, depo-progesterone
injections, a barrier contraceptive such as a condom with or without spermicide cream
or gel, diaphragms or cervical cap with or without spermicide create or gel, or an
intrauterine device (IUD). Some additional pregnancy-related items you should be
aware of include:

We do not know the effect of this investigational therapy on babies before they
are born, or on nursing children. You should not breast feed your child while
participating in this study.

Pregnancy tests, paid for by the study team, will be done on all women who
might be able to get pregnant at the start of the study.

Men should not father children while in the study.

If you or your partner becomes pregnant during the study you should notify the
Study Doctor right away.

If you are a woman and you are planning to get pregnant, you should not be in
the study.
There may be uncommon or previously unknown risks that might occur. You should
report any problems to the study staff.
You have the right to ask any questions about the potential and/or known hazards of
this study at any time. You will be asked to tell the study doctor about any possible side
effects you might have at any time during the study.
HIV Testing
For HIV testing, you will be signing a separate consent form. By law, we must report test
results to the Florida Department of Health with information identifying you if you test
positive.
NAME: _________________________________
MRN: __________________________________
AGE: ___________ DOB: _____/_____/______
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If the blood test is positive for HIV infection there is also the possibility of emotional
distress and that your status in your workplace or other social organizations will be
impacted if you or others with knowledge of your HIV infection disclose this information.
BENEFITS
If you agree to participate in this study, there may be no direct benefit to you. There is a
chance that the human cells injected into your heart may improve your heart’s ability to
pump blood and you may feel better. However, because there is not much known about
the effects of human mesenchymal stem cells in humans, we do not know if you will
benefit from taking part in this study. Your condition may continue to become worse
despite receiving this experimental treatment.
The knowledge gained from this study may help others with chronic heart problems.
ALTERNATIVES
You may choose not to participate in this study. Alternative forms of therapy exist for
patients who have chronic heart problems. If you choose not to take part, you can
receive the standard therapy for people who have had a heart attack. Optimal
medication management would be the most common alternative therapy for you.
You do not have to join this study. If you do not join, your care at the University of
Miami will not be affected.
COSTS
Some of the tests and procedures in this study are research-related. The University of
Miami is sponsoring this study through a grant from the National Institutes of Health and
will pay for all research-related procedures and tests. BioCardia, Inc. will pay for the
catheter. You, or your insurance company, will be responsible for medical treatment
related to your heart condition, which includes tests and procedures related to your
medical care prior to and following your catheterization. If you have insurance, your
insurance company may or may not pay for these costs. If you do not have insurance,
or if your insurance company refuses to pay, you will be expected to pay. You should
check with your insurance company to determine whether these costs will be covered
NAME: _________________________________
MRN: __________________________________
AGE: ___________ DOB: _____/_____/______
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and whether there will be costs for any co-payments or deductibles. For further
information of what may or may not be billable to your insurance company, please
contact the study team and your insurance company.
INCENTIVES/PAYMENTS TO PARTICIPANTS
We will assist you for transportation, parking fares, and your time. You will receive $25
per visit for months 1-6, the month 12 visit and the month 13 visit. These payments are
meant to cover the time required to complete these study visits and all necessary travel
and parking expenses.
COMPENSATION FOR STUDY-RELATED INJURY
You may be exposed to risk of injury from participation in this study.
If injury directly related to the catheter occurs, BioCardia (the manufacturer of the
device) will cover the cost of treatment of these injuries. Funds to compensate for pain,
expenses, lost wages and other damages caused by injury from the catheter are not
routinely available.
If injury occurs as a result of other study related procedures (separate from the
catheter), treatment will, in most cases, be available. If you have insurance, your
insurance company may or may not pay for these costs. If you do not have insurance,
or if your insurance company refuses to pay, you will be expected to pay. Funds to
compensate for pain, expenses, lost wages and other damages caused by injury are not
routinely available.
VOLUNTARY PARTICIPATION / WITHDRAWAL FROM STUDY
Your participation in this study is voluntary. You may refuse to participate, or withdraw
from the study at any time, without penalty or loss of benefits to which you are otherwise
entitled. This will not affect the medical care you receive from the Study Doctor or the
University of Miami. You must tell the Study Doctor if you wish to stop taking part in the
study.
NAME: _________________________________
MRN: __________________________________
AGE: ___________ DOB: _____/_____/______
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Your participation in this study may be discontinued, without your consent, at any time
by the Study Doctor, if:
o the doctor believes that participation in the study is no longer in your best interest
o new information about the study treatment or other treatments become available
o you are unable to meet the requirements of the study
o the study is cancelled
o you are randomized to Group 1 (autologous hMSCs) and your hMSCs fail to
grow
The Institutional Review Board (IRB), Data and Safety Monitoring Board (DSMB), or
regulatory authorities may also discontinue your participation in the study. The study
doctors for this study are:
Joshua M. Hare, MD
Biomedical Research Building
1501 NW 10th Ave., Suite 824
Miami, FL 33136
Alan W. Heldman, MD
Clinical Research Building
1120 NW 14th Street, Suite 1119
Miami, FL 33136
If you cancel your permission after you have started in the study, the study staff and the
Study Doctor will stop collecting your health information. Although they will stop collecting
new information about you, they may need to use the data already collected to evaluate
the study results.
Student Rights
If you are a student, your desire not to participate, or your request to withdraw from the
study, will not affect your grades or other academic standings within the University.
Employee Rights
If you are an employee of the University, your decision to participate in or to withdraw
from the study, will not affect your employment within the University.
CONFIDENTIALITY
By signing this consent, you authorize the Investigator and his staff to access your
medical records and associated information as may be necessary for purposes of this
study. Your records and results will not be identified as pertaining to you in any
NAME: _________________________________
MRN: __________________________________
AGE: ___________ DOB: _____/_____/______
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publication without your expressed permission. The Investigator, and his collaborators
and staff, will consider your records confidential to the extent permitted by law. The
Food and Drug Administration (FDA) and Department of Health and Human Services
(DHHS) may review these research records. Your records may also be reviewed for
audit purposes by authorized University of Miami employees or other agents who will be
bound by the same provisions of confidentiality.
You will be assigned a unique code number when participating in this study. All
information about you that is collected will be linked to this number. The key to the code
will be kept in a locked file in the Study Investigator’s office. Only authorized members
of the Study Investigator’s team will have access to the room. Information about you will
also be processed and/or stored on a computer which is password protected.
The study site personnel may use your information to notify you of appointments, send
you appointment reminders, or schedule additional appointments.
WHOM TO CONTACT
If, at any time you have any questions about the study, you may contact Joshua M.
Hare, MD at 305-243-1999 or Alan Heldman, MD at 305-243-5138.
In case of study-related injury, please contact Joshua M. Hare, MD at 305-243-1999 or
Alan Heldman, MD at 305-243-513
If you have any questions relating to your rights as a research subject, please contact
the University of Miami’s Human Subject Research Office (HSRO), at 305-243-3195.
NAME: _________________________________
MRN: __________________________________
AGE: ___________ DOB: _____/_____/______
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AGREEMENT FOR BONE MARROW CELL STORAGE
Most of the collected bone marrow specimens will be destroyed at the completion of this
study. However, the research team would like to request your permission to use these
samples for future unidentified stem cell-related research. Only research approved by
an institutional review board (IRB) will be allowed to use these samples and information
for future studies.
Please select one of the choices below to indicate your preference regarding using your
samples and information for future research.
[ ] a. I give permission for my bone marrow sample and information to be utilized for
this study and for future stem cell-related research.
[ ] b. I DO NOT give permission for my biological samples and information to be
utilized for this study and for future stem cell-related research.
NAME: _________________________________
MRN: __________________________________
AGE: ___________ DOB: _____/_____/______
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AGREEMENT OF DECISION TO PARTICIPATE
You will receive a copy of this signed informed consent form.
I have read this consent, which is printed in English (a language which I read and
understand). This study has been explained to my satisfaction and all of my questions
relating to the human bone marrow cells and mesenchymal stem cells (investigational
treatment), the study procedures, risks and discomforts, and side effects have been
answered. If I have any further questions regarding this study, or in the event of a
study-related injury, I should contact the appropriate person named above. Based on
this information, I voluntarily agree to give permission (consent) for me to take part in
this study.
________________
Signature of Participant
__________________
Date
________________
Printed Name of Participant
_______________
Signature of Person Obtaining Consent
____________
Date
________________
Printed Name of Person Obtaining Consent
NAME: _________________________________
MRN: __________________________________
AGE: ___________ DOB: _____/_____/______
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