Vasopressin CPR Trial

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Vasopressin CPR Trial

• Community Consultation
• Childrens Medical Center
• and The University of Texas
• Southwestern Medical Center

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Principal Investigator

• Tia Tortoriello Raymond, M.D.
• University of Texas Southwestern Medical Center
• Childrens Medical Center Dallas
• Department of Pediatrics
• 1935 Medical District Drive
• Dallas, TX 75235
• [phone]

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Sub-investigator

• Timothy G. Carroll, M.D.
• University of Texas Southwestern Medical Center
• Childrens Medical Center Dallas
• Department of Pediatrics
• 1935 Medical District Drive
• Dallas, TX 75235
• [phone]

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Who is sponsoring the study and how many patients
will be enrolled?

• The study is funded by the primary investigator
  and is not sponsored by industry
• Approximately 130 subjects will be enrolled in
  this study

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Study Purpose

• To evaluate the use of Vasopressin
  when given to
  pediatric patients in refractory cardiopulmonary
  arrest

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What is Cardiopulmonary Arrest?

• The person looses consciousness, stops breathing,
  and looses their pulse and blood pressure
• All the organs of the body are receiving no blood
  flow and hence no oxygen
• Cardiopulmonary resuscitation (CPR) is begun to
  help restart breathing and help the heart resume
  beating
• Will lead to death if CPR not performed, may lead
  to death if CPR is performed

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Can Cardiac Arrest be Reversed?

• Brain death and permanent death start to occur in
  4-6 minutes after cardiac arrest
• Can be reversed if treated within MINUTES
• Survival reduced by 7 to 10 percent with every
  minute that passes without CPR
• Few attempts at resuscitation succeed after 10
  minutes

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How do we treat Cardiopulmonary Arrest?

• Giving breaths and oxygen
• Chest compressions
• Defibrillation (electric shock to heart to
  restore normal heartbeat)
• Medications to restart heart
• Fluids
• ? Resuscitation ECMO

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Standard of Care for CPR

• Pediatric Advanced Life
• Support (PALS) Guidelines
• - protocol endorsed by
• the American Heart
• Association for pediatric
• patients

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Standard of Care for CPR

• Advanced Cardiac Life
• Support (ACLS)
• Guidelines
• - protocol endorsed by
• the American Heart
• Association for adults

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Standard of Care Limitations

• Excessive medications can cause
• Severely increased blood pressure
• Abnormal heart rhythms
• Depressed heart function
• Lack of oxygen and blood flow can cause
• Tissue damage to vital organs such as the brain,
  kidneys, intestines, and heart itself
• Acid build up in the blood

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Need for Improved Outcome

• More than 95 percent of cardiac arrest victims
  die before reaching the hospital
• Pediatric in-hospital cardiac arrest survival
  rate is extremely poor 27
• Those who do survive may have severe brain injury

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Need for Improved Outcome

• To better understand how to treat cardiac arrest
• Determine ways to improve survival after cardiac
  arrest

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What is Vasopressin ?

• Vasopressin is a drug approved by the Food and
  Drug Administration (FDA) for patients with
• Diabetes Insipidus (extreme thirst and frequent
  urination)
• Abdominal distention after surgery

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• Vasopressin is commonly used for the treatment
  of other disorders not currently approved by the
  FDA.
• The use of Vasopressin in this manner is
  referred to as Off-Label

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Current Standard of CareOff-Label

• The use of Vasopressin is recognized
• By the American Heart Association and European
  Resuscitation Council for use in the management
  of adult patients in cardiac arrest
• As a standard treatment for shock due to
  infection

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Vasopressin Experience in CPR

• In animal studies vasopressin has been shown to
  improve vital organ blood flow, particularly to
  the brain
• Leads to improved outcomes to get the heart
  restarted and survive
• Beneficial effects have been observed in adult
  human studies
• ALL studies have shown vasopressin to be equal or
  superior to epinephrine (current standard of care)

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Why Use Vasopressin?

• To improve the survival of pediatric patients
  during and after cardiac arrest
• To understand the impact that Vasopressin has on
  the treatment of pediatric patients in cardiac
  arrest

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Potential Benefits of Vasopressin

• Increase the proportion of patients with return
  of a normal heart rate and blood pressure
• Increase the likelihood of survival
• Increase the proportion of patients with
  favorable neurologic outcome

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FDA Review

• Tia Tortoriello Raymond, M.D. received clearance
  to proceed with this study from the Food and Drug
  Administration (FDA)
• The FDA authorized the use of exception from
  informed consent requirements for this study

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Patient Protection

• The Institutional Review Board (IRB) is a
• group of medical, scientific, and nonscientific
• members of the community
• Reviews all proposals for research on humans
• Assures patient safety
• Monitors community feedback

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Patient Protection

• The UTSW IRB will decide whether or not to allow
  Childrens Medical Center to conduct the
  Vasopressin CPR trial BASED ON SCIENTIFIC MERIT
  AND COMMUNITY FEEDBACK
• An independent data monitoring committee will
  oversee the trial
• The FDA will be kept informed of the trials
  progress

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What is Informed Consent?

• A process by which patients make informed
  decisions about participating in research
  studies.

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Informed Consent

• Traditionally required for all research studies
• Research studies compare 2 treatments (standard
  vs. investigational)
• Doctors describe each of these potential
  treatments
• Patients are informed of the potential risks and
  potential benefits associated with each of these
  treatments
• Patients choose whether to participate in the
  study

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What is Exception from Informed Consent?

• Patients are enrolled in a
• research study without giving
• their informed consent

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• A federal regulation (21 CFR 50.24), created
• in 1996, allows certain studies that meet the
• following criteria to use this exception
• Patients lives must be at risk
• Available treatments are not satisfactory
• Patients are unable to give consent
• Potential risks are reasonable, participation in
  the research could provide a direct benefit
  (increased survival) to the patient
• The research could not be practicably carried out
  without an exemption

http//www.fda.gov/ora/compliance_ref/bimo/err_gui
de.htm
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Consent Safeguards

• Obtaining consent is not feasible because
  intervention must be administered before consent
  from the subjects LAR is feasible.
• Obtaining consent is not feasible as there is no
  reasonable way to identify prospective
  individuals likely to become eligible for
  participation.

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Consent Safeguards

• The IRB has reviewed and approved the informed
  consent procedure and document.
• Additional protections of the rights and welfare
  of subjects provided through a process of
  community consultation.
• Additional protections of the rights and welfare
  of subjects provided through a process of public
  disclosure.

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Consent Safeguards

• Procedures must be in place to inform at the
  
• earliest feasible opportunity each subject or
• LAR of inclusion in the study.
• The patient or a legally authorized
  representative may decide to withdraw the patient
  at any time without penalty or loss of benefits

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Community Consultation

• Community consultation refers to ensuring the
  communities involved are provided an opportunity
  to discuss the proposed clinical investigation.
• Following completion of the study information
  about the study results must be disclosed
• to the community where the research was done
• the research community should have access to
  comprehensive summary data

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Community Consultation

• Must advise the community at risk of the study
  and ways to opt out
• For in-hospital resuscitation study this
  community would be the families/staff of the
  Pediatric ICU at CMC
• Focus group discussions with physicians, nurses,
  pharmacists, families
• Posters, brochures, website and study personnel
  available to explain the study in the PICU
• Press release and letter to all medical staff

www.childrens.com/Research/Vasopressin/index.cfm
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Procedure to Opt Out

• If a parent decides to opt out of the study, a
  sign will be placed on the patients bed that
  will clearly delineate that the patient is not
  included in the study.

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Public Disclosure

• Public disclosure refers to informing these
  communities about the study prior to starting and
  following completion.
• Prior to start of the study -- public disclosure
  of sufficient information to describe
• the nature and purpose of the study
• the fact that informed consent will not be
  obtained for most study subjects

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Trial Design After patient suffers a cardiac
arrest

• Patients will be randomly assigned to either one
  of two groups (like flipping a coin)
• Control Test
• Epinephrine Only
• (standard of care)

50
50
Epinephrine and Vasopressin
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Who Would Be Included?

• Patients who suffer a cardiac arrest in the
  Pediatric Intensive Care Unit
• Who are 0-18 years old
• Who require more than one dose of a medication to
  restart the heart

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Who Would Be Excluded?

• Patients who do not require chest compressions or
  defibrillation
• Patients who do not require epinephrine
• Patients who are pregnant
• Patients with known orders not to resuscitate

• Patients in the custody of the State of Texas
• Any patient whose parent or guardian opts out
  of the study
• Any patient whose attending physician opts out
  of the study

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Potential Risks of Vasopressin

• The risks of vasopressin are equal or less than
  the risks associated with epinephrine (current
  standard of care)
• Risks include
• Increase in liver enzymes, decrease in platelets
  (helps blood clot)
• Abnormal heart rhythm, low sodium, allergic
  reaction, and skin necrosis if the medications
  leaks out of the vein
• Increase in urine output
• Unforeseen happenings

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After the study is completed

• The results of the study will be revealed to the
  community after the trial has been completed
• The results of this study could change the
  protocol by which every pediatric patient that
  experiences cardiac arrest is resuscitated

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Questions or Comments?
Phone Number [phone] or [phone]