Trial of Vasopressin and Epinephrine to Epinephrine Only for In-Hospital Pediatric Cardiopulmonary Resuscitation (Vasopressin)

Study Description

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Brief Summary:

Cardiac arrest has a very poor prognosis, especially with prolonged efforts at resuscitation, and unfortunately, survivors are often severely neurologically impaired. CPA in children is often the result of a prolonged illness rather than a sudden, primary cardiac event as is frequent in adults. This necessitates that resuscitation research must be conducted separately for pediatric and adult patients. Authorities currently endorse the use of epinephrine for restoring spontaneous circulation based on its ability to maintain diastolic blood pressure and subsequent blood flow to the heart during resuscitation. However, human studies have shown no clear survival benefit of epinephrine and have elucidated concerning adverse effects. Recently, both the European Resuscitation Council and the American Heart Association have recognized the use of vasopressin as a promising vasoconstrictor and an alternative or adjunct to epinephrine in the resuscitation of adults. Vasopressin causes profound vasoconstriction without the adverse effects of epinephrine and is associated with improved blood flow to the heart and brain. This increased cerebral blood flow has been associated with better neurologic outcome in animal studies. In light of compelling animal and human studies of combined vasopressin and epinephrine, pediatric trials are indicated for vasopressin usage in pediatric CPR. This study will evaluate the addition of the administration of vasopressin to standard advanced CPR therapy (epinephrine alone) for pediatric patients that experience in-intensive care unit CPA to assess for improved time to return of spontaneous circulation (ROSC), survival to 24 hours, survival to hospital discharge, and neurologic outcome. When a patient experiences a CPA, standard Pediatric Advanced Life Saving (PALS) protocols as endorsed by the American Heart Association will be initiated. This will include receiving epinephrine as the first vasopressor medication. Patients will then be randomized to receive vasopressin (treatment group) or epinephrine (control group) as the second vasopressor medication, if needed. If more then two doses of vasopressor medication is required in either group, epinephrine will be administered according to the PALS algorithm until the end of the event. All CPA events meeting inclusion criteria will be entered into the National Registry of Cardiopulmonary Resuscitation (NRCPR) Database, which tracts all CPA events at Children's Medical Center Dallas. Prior to commencement of the RCT, a pilot trial of 10 patients will be completed to assess preliminary safety, feasibility, and effectiveness of combination epinephrine-vasopressin for pediatric in-intensive care unit CPA refractory to initial epinephrine dosing. All pilot patients will receive vasopressin as the second vasopressor medication.

Condition or disease	Intervention/treatment	Phase
Cardiopulmonary Arrest; Cardiac Arrest	Drug: Vasopressin; Drug: Epinephrine	Phase 1

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Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	130 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Prospective, Randomized, Controlled Trial of Combination Vasopressin and Epinephrine to Epinephrine Only for In-Intensive Care Unit Pediatric Cardiopulmonary Resuscitation
Study Start Date :	April 2008
Estimated Primary Completion Date :	April 2011
Estimated Study Completion Date :	December 2011

Arms and Interventions

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Arm	Intervention/treatment
Experimental: 1; Pediatric patients that experience in-hospital CPA who remain in cardiac arrest despite CPR and an initial, standard dose of epinephrine (0.01 mg/kg), will be randomly assigned to receive vasopressin (0.8 units/kg) rescue as the second vasopressor medication.	Drug: Vasopressin; One dose of vasopressin (0.8 units/kg) intravenously rescue as the second vasopressor medication.; Other Name: Pitressin
Active Comparator: 2; Pediatric patients that experience in-hospital CPA who remain in cardiac arrest despite CPR and an initial, standard dose of epinephrine (0.01 mg/kg), will be randomly assigned to receive standard dose epinephrine (0.01 mg/kg)rescue as the second vasopressor medication.	Drug: Epinephrine; One standard dose epinephrine (0.01 mg/kg) intravenously rescue as the second vasopressor medication.; Other Name: Adrenaline

Outcome Measures

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Primary Outcome Measures :

1. Combination vasopressin and epinephrine (CPA refractory to cardiopulmonary resuscitation and initial epinephrine dosing) will increase the proportion of patients surviving to hospital discharge by 25% compared to epinephrine alone. [ Time Frame: Immediate ]

Secondary Outcome Measures :

1. Combination vasopressin and epinephrine will decrease the time to ROSC [ Time Frame: Immediate ]
2. Vasopressin and epinephrine will improve the proportion of CPA survivors with favorable neurologic outcome (short-term Pediatric Overall Performance Category) [POPC] score discharge of 1-3 or unchanged from hospital admission at the time of hospital . [ Time Frame: Period of hospitalization ]
3. Vasopressin and epinephrine will improve the proportion of CPA survivors with favorable neurologic outcome (short-term Pediatric Cerebral Performance Category) [PCPC] score of 1-3 or unchanged from hospital admission at time of hospital discharge. [ Time Frame: Period of Hospitalization ]
4. Combination vasopressin and epinephrine will improve 24 hour survival. [ Time Frame: 24 hrs ]
5. Combination vasopressin and epinephrine will decrease the proportion of patients who require prolonged CPR (CPR > 20minutes) to achieve sustained ROSC. [ Time Frame: Immediate ]
6. Combination vasopressin and epinephrine will increase organ recovery in those patients who meet brain death criteria following the CPA event. [ Time Frame: Period of hospitalization ]
7. Combination epinephrine and vasopressin will improve rates of return of spontaneous circulation (ROSC) [ Time Frame: Immediate ]

Eligibility Criteria

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Ages Eligible for Study:	up to 18 Years (Child, Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• All children, ages 0 to 18 years, admitted to the PICU who experience CPA requiring either chest compressions and/or defibrillation. This will include males, females and Spanish speaking individuals.
• Patients must require at least 2 doses of vasopressor medication during the CPA event (all patients would receive epinephrine as first dose, followed by either epinephrine or vasopressin as second dose depending on randomization, all subsequent doses required would be epinephrine) given via any route (intravenous, intraosseous, or endotracheal).

Exclusion Criteria:

• Do Not Attempt Resuscitate (DNAR) patients
• Chemical code only (i.e., no CPR/defibrillation)
• Events not requiring chest compressions and/or defibrillation
• Events with a pulse requiring synchronized or unsynchronized cardioversion
• Successful internal cardiac device defibrillation of Vfib/pVT that initiates the resuscitation event
• Defibrillation for Vfib/pVT without administration of a vasopressor
• All patients in the custody of the State of Texas
• Any patient whose parent or guardian "opts out" of the study
• Any patient who is pregnant
• Any patient whose attending physician "opts out" of the study
• Any patient who does not consent to follow up data collection

Contacts and Locations

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Contacts

Contact: Tia Tortoriello Raymond, M.D.	9725337175	Tiaraymond@me.com
Contact: Timothy G Carroll, M.D.	214-456-7614	Timothy.Carroll@Childrens.com

Locations

United States, Texas
Universtity of Texas Southwestern, Children's Medical Center	Recruiting
Dallas, Texas, United States, 75235
Contact: Tia Tortoriello Raymond, M.D. 214-456-2281 Tia.Tortoriello@Childrens.com
Principal Investigator: Tia Tortoriello Raymond, M.D.
Sub-Investigator: Timothy G Carroll, M.D.
Sub-Investigator: Vivian Dimas, M.D.
Sub-Investigator: Daniel Stromberg, M.D.
Sub-Investigator: Craig Huang, M.D.

Sponsors and Collaborators

University of Texas Southwestern Medical Center

Children's Medical Center Dallas

Investigators

Principal Investigator:	Tia Tortoriello Raymond, M.D.	Universtiy of Texas Southwestern

More Information

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Responsible Party:	Tia Tortoriello Raymond, MD, Medical City Children's Hospital
ClinicalTrials.gov Identifier:	NCT00628550 History of Changes
Other Study ID Numbers:	082007-065
First Posted:	March 5, 2008
Last Update Posted:	June 28, 2010
Last Verified:	June 2010

Keywords provided by University of Texas Southwestern Medical Center:

cardiac arrest; cardiopulmonary arrest; vasopressin	epinephrine; pediatrics; in hospital cardiopulmonary resuscitation

Additional relevant MeSH terms:

Epinephrine; Racepinephrine; Epinephryl borate; Heart Arrest; Heart Diseases; Cardiovascular Diseases; Vasopressins; Arginine Vasopressin; Vasoconstrictor Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action	Physiological Effects of Drugs; Adrenergic beta-Agonists; Bronchodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Anti-Asthmatic Agents; Respiratory System Agents; Mydriatics; Sympathomimetics; Hemostatics; Coagulants; Antidiuretic Agents; Natriuretic Agents