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: Neuromuscular Blockade for the Management of Post Cardiac Arrest Patients
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, Alex Weissman, 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
You or 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. (From this point on, “you” will refer to either you or your loved one.) The
main purpose of this study, sponsored by the American Heart Association, is to test the
effects of rocuronium, a drug that will relax/stop muscles from moving, for patients after
they have had a cardiac arrest.
Cardiac arrest is a very serious condition. You have already spoken to your provider
about the different treatment options, which include lowering the body temperature
(targeted temperature management or 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. Neuromuscular blockades (NMB) are a class of medications that paralyze your
muscles. NMBs are already used as treatment in some patients after a cardiac arrest to
reduce side effects from the TTM, such as shivering. They have also been shown to be
beneficial in other critically ill patients. Ideally after a cardiac arrest the body’s resources
should be focused to the recovery process. Frequently these resources will be used by
other non-essential activities, such as involuntary muscle movements. This is a waste of
resources that your body desperately needs to heal. Your brain in particular is very
sensitive to a lack of oxygen. We do not know exactly how NMB benefits critically ill
patients but we are proposing that it works by allowing resources to be focused on the
vital organs rather than muscles.
People who survive a cardiac arrest may continue to be at risk of death. This study is
being done to develop treatments that improve survival and reduce this risk. In this study,
we are evaluating if the use of a NMB after cardiac arrest is beneficial, and to describe the
body’s response this treatment. Specifically the NMB we will use is rocuronium, which is
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Institutional Review Board
Approval Date: 3/7/2017
Renewal Date: 3/6/2018
IRB #: PRO14060504
commonly used in the intensive care unit. NMBs will allow your body’s resourses to be
focused on your vital organs rather than your muscles. The NMB will keep you from
shivering and keep you from resisting the work of the ventilator (breathing machine). It
has also been suggested that NMB might help to decrease inflammatory markers in your
blood that have been associated with a worse outcome. If giving NMB is helpful and
effective, it might become something that we give routinely to patients after cardiac arrest
in the future.
Rocuronium is already used in clinical care and safe dosages have already been
determined. We will abide by these dosages and any safety considerations.
This study is being performed in partnership with Beth Israel Deaconess Hospital
(Boston, MA) and Brigham and Women’s Hospital (Boston, MA). Blood samples and
data, without names or any personal identifying information, may be shared with the
investigators at those sites. The University of Pittsburgh plans to enroll approximately 15
subjects aged 18 years or older.
DESCRIPTION OF STUDY DETAILS
1. Screening Procedures:
Screening procedures are tests and procedures that will be done to determine if you are
eligible to take part in the research study. For this research study, the screening procedures
will be a review of your medical record to see if you qualify for the study.
2. Randomization Procedures:
You will be randomly assigned (like the flip of a coin) to receive either a set dose and a
continuous drip of rocuronium or a placebo along with standard of care for 24 hours. You
have a 1 in 2 chance of receiving either the drug or the placebo. You will not be able to
choose the study group to which you will be assigned.
Depending upon the group to which you are assigned, you 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 provider/care team will be informed what
group you are in.
If one treatment arm is found to be less effective then the other while you are taking part
in the study, you will be informed and further treatment will be discussed.
3. Research Procedures:
If you qualify to take part in this research study, you will undergo these research
procedures:
A. Study Drug Dosing:
You will be administered either the rocuronium or the placebo. If you are
randomized to receive the rocuronium, you will first be sedated then you will
receive a standard dose of rocuronium
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University Of Pittsburgh
Institutional Review Board
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Renewal Date: 3/6/2018
IRB #: PRO14060504
a) The infusion will be continued for about 24 hrs
b) If you receive the placebo, you will receive a 50mL dose of a saline solution
(lightly salted water). The control arm will be “usual care” and the research
team will not prevent the use of NMB if clinically indicated thereby
preventing any potential harm to this group.
B. Blood Draws:
a) You will have blood draws at enrollment, and at 12 and 24 hours later, for a
total of 80 mLs of blood. The blood will be collected via a needle stick in
your arm if you do not already have an existing line in place. The blood is
being collected to look at lactate levels, which can tell us how well oxygen
and blood is flowing through your body.
b) There is also an optional blood draw that will take place just before you
receive the study drug, and again 24 hours after you have received the study
drug. These blood tests are looking at biomarkers, which test the way your
body responds to the study drug. You are under no obligation to participate
in this blood draw, even if you participate in the rest of the study. You will
have the option to participate or decline participation at the end of this form.
C. Data Collection:
We will record the following information that would be collected from you
anyway as part of usual care (i.e. the measurements are not being done for
research):
a) We will record information about your past medical history,
demographics, the details of your heart attack and all the emergency and
hospital treatment that you have received up until this point.
b) At time points at 0 hours, 12 hours, 24 hours, and 36 hours after
enrollment, we will follow along in your chart and record lab results from
your routine care.
c) We will record your vital signs (for example, heart rate, breathing rate,
temperature, blood pressure).
d) We may record information about the circumstances before and the method
in which you were resuscitated. As well as information about your health
history and medications that you take on a regular basis.
4. Monitoring/Follow-Up Procedures:
Procedures performed to evaluate the effectiveness and safety of the research procedures
are called “monitoring” or “follow-up” procedures. For this research study, the
monitoring/follow-up procedures include:
a) When you are discharged, we will record information about your length of
stay and final diagnosis.
Risks and Benefits: Multiple studies with the same dosages of rocuronium over a short
time course (similar to this study) have not revealed any increased risk or potential harm.
The potential side effects of rocuronium include muscle weakness and very rare allergic
reactions. Emergency treatment will be available to treat allergic reactions. Other risks
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University Of Pittsburgh
Institutional Review Board
Approval Date: 3/7/2017
Renewal Date: 3/6/2018
IRB #: PRO14060504
include cross-sensitivity with other blocking agents and prolonged paralysis. To prevent
and minimize these risks, we will not enroll you if you’ve taken any other nerve blocking
agent, and we will closely monitor your progress until you no longer feel symptoms of
paralysis. Rocuronium is well tolerated and frequently used by all enrolling centers in
the care of critically ill patients. We will follow standard care procedures stating that
post-cardiac arrest patients treated with rocuronium will receive brain activity
monitoring. This will reveal any seizure activity to the treating clinical team in real-time.
Uncommon risks associated with sedation include coma, loss of airway reflexes and low
blood pressure. There is also a rare risk of anaphylaxis, which is a severe allergic
reaction. You will be monitored and treated for any issues that arise after you are
sedated.
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 you will have
an intravenous line from which we may draw, and so the blood draw will be painless.
There is a very small risk that air or microorganisms may be introduced in your blood
stream, but many steps will be taken to keep this risk at an absolute minimum at blood
draws will be aligned with clinical blood draws if feasible.
There is a risk of death after surviving cardiac arrest. While it is not known if the study
treatment will improve survival, it is unlikely to increase the risk of death.
As a result of your participation in this study, you are at risk for side effects listed in this
section. You should discuss these with the investigator and with your regular doctor if
you choose.
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 identifiable information.
However, if your participation becomes known, it could create a problem or hardship for
you depending upon the type of information disclosed.
POSSIBLE BENEFITS
It is not possible to predict whether you will benefit directly from participation in this study.
However, your participation may help others in the future as a result of knowledge gained
from the research.
Costs and Payments: You will not be paid for participating in this study. You and your
insurer or third party payer will not be billed for research-related services or services
related solely to the research. However, you, or your insurer, will be billed for all other
usual care services, and/or services not connected with the study, just as you would if not
in the study.
Alternatives to Participation: If you decide to not participate in this study, your doctor
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University Of Pittsburgh
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Renewal Date: 3/6/2018
IRB #: PRO14060504
will continue to treat you or your loved one according to their usual standard of care
treatment plan.
Compensation for Injury: If you believe that the research procedures have injured you,
immediately contact the Principal Investigator, Dr. Rittenberger. The hospitals of UPMC
will provide emergency medical treatment for injuries solely and directly related to your
participation in this research study. 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.
Confidentiality: In order to conduct this research study we will record current and/or
future identifiable information from your hospital records that are related to this cardiac
arrest. Only the investigators named on this form or their staff will have access to this
information. The information will be stored indefinitely. Any information we include in
our research records will be shared only with other members of our medical research
team, Beth Israel Deaconess Hospital, the study’s Data Safety and Monitoring Board, and
required federal and local agencies providing oversight, including the University’s
Research Conduct and Compliance Office and National Institutes of Health. We will
store this information indefinitely.
Any information about you obtained from this research, including your 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
involvement in this research will be stored in a secure location. Your identity on these
records and the samples will be indicated by your subject identification number rather
than by your name, and the information linking your subject identification number with
your identity will be kept separate from the research records. You will not be identified
by name in any publication of the research results or in any other scientific publications
or presentations unless you sign a separate consent form giving your permission (release).
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.
Right to Participate or Withdraw from Participation: Participation is completely
voluntary and a decision to participate, or to later withdraw from the study, will not affect
either your current or future medical care at UPMC. If you agree to participate and later
change your mind, or if you later decide to withdraw, a written and dated notice of this
decision needs to be sent to the investigator. You 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
you withdraw unless you specifically request these be destroyed.
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Approval Date: 3/7/2017
Renewal Date: 3/6/2018
IRB #: PRO14060504
If the investigators or treating providers feel that you or your loved one cannot complete
the study requirements safely, they may withdraw you or your loved one from the study.
Optional Biomarker Blood Draw
Please initial whether you permit the collection of the additional blood samples as described on page 3: ______ YES, I give my permission for blood samples to be collected for the biomarker testing ______ NO, I do not give my permission for blood samples to be collected for the biomarker testing Page 6 of 9
University Of Pittsburgh
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Renewal Date: 3/6/2018
IRB #: PRO14060504
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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. A copy of
this consent form will be given to me.
___________________________
Participant’s Signature
________________________
Printed Name of Participant
____________
Date/Time
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)
_______________________
Relationship to Participant
____________________________
Representative’s Signature
_______________________
Date/Time
____________________________
Witness Signature
______________________
Date /Time
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Institutional Review Board
Approval Date: 3/7/2017
Renewal Date: 3/6/2018
IRB #: PRO14060504
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
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University Of Pittsburgh
Institutional Review Board
Approval Date: 3/7/2017
Renewal Date: 3/6/2018
IRB #: PRO14060504
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 through the exception from informed
consent requirement or 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
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
continued 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.
_______________________
Investigator’s Name (Print)
_____________________
Investigator’s Signature
____________
Date/Time
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University Of Pittsburgh
Institutional Review Board
Approval Date: 3/7/2017
Renewal Date: 3/6/2018
IRB #: PRO14060504