Vasopressin CPR Trial

Community Consultation

Children’s Medical Centerand The University of Texas

Southwestern Medical Center

Principal Investigator

Tia Tortoriello Raymond, M.D.

University of Texas Southwestern Medical Center

Children’s Medical Center Dallas

Department of Pediatrics

1935 Medical District Drive

Dallas, TX 75235

(214) 456-2281

Sub-investigator

Timothy G. Carroll, M.D.

University of Texas Southwestern Medical Center

Children’s Medical Center Dallas

Department of Pediatrics

1935 Medical District Drive

Dallas, TX 75235

(214) 456-7614

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

Study Purpose

To evaluate the use of Vasopressin when given to

pediatric patients in refractory cardiopulmonary arrest

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

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

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

Standard of Care for CPR

• Pediatric Advanced Life

Support (PALS) Guidelines

- protocol endorsed by

the American Heart

Association for pediatric

patients

Standard of Care for CPR

• Advanced Cardiac Life

Support (ACLS)

Guidelines

- protocol endorsed by

the American Heart

Association for adults

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

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

Need for Improved Outcome

• To better understand how to treat cardiac arrest

• Determine ways to improve survival after cardiac arrest

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

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”

Current Standard of Care“Off-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

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)

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

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

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

Patient Protection

The Institutional Review Board (IRB) is agroup of medical, scientific, and nonscientificmembers of the community

• Reviews all proposals for research on humans

• Assures patient safety

• Monitors community feedback

Patient Protection

• The UTSW IRB will decide whether or not to allow Children’s 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 trial’s progress

What is Informed Consent?

A process by which patients make informed decisions about

participating in research studies.

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

What is Exception from Informed Consent?

Patients are enrolled in a research study without giving

their informed consent

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_guide.htm

Consent Safeguards

• Obtaining consent is not feasible because intervention must be administered before consent from the subject’s LAR is feasible.

• Obtaining consent is not feasible as there is no reasonable way to identify prospective individuals likely to become eligible for participation.

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.

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

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

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

Procedure to “Opt Out”

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

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

Patients will be randomly assigned to either one of two groups (like flipping a coin)

Control Test

Epinephrine Only (standard of care)

Trial Design: After patient suffers a cardiac arrest

Epinephrine and

Vasopressin

50% 50%

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

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

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

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

Questions or

Comments?

Phone Number: (214) 456-7614 or

(214) 456-2281