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

NCT00628550 | Completed Phase 1 DMC

• 1 other identifier: 082007-065
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 1

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.

Conditions

Cardiopulmonary Arrest; Cardiac Arrest

Keywords

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

Outcome Measures

Primary Outcomes (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.

  Immediate

Secondary Outcomes (7)

• Combination vasopressin and epinephrine will decrease the time to ROSC

  Immediate

• 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 .

  Period of hospitalization

• 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.

  Period of Hospitalization

• Combination vasopressin and epinephrine will improve 24 hour survival.

  24 hrs

• Combination vasopressin and epinephrine will decrease the proportion of patients who require prolonged CPR (CPR > 20minutes) to achieve sustained ROSC.

  Immediate

Study Arms (2)

1

EXPERIMENTAL

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

2

ACTIVE COMPARATOR

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

Interventions

Vasopressin DRUG

One dose of vasopressin (0.8 units/kg) intravenously rescue as the second vasopressor medication.

Also known as: Pitressin

1

Epinephrine DRUG

One standard dose epinephrine (0.01 mg/kg) intravenously rescue as the second vasopressor medication.

Also known as: Adrenaline

2

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• Children's Medical Center Dallas: collaborator

Study Sites (1)

Universtity of Texas Southwestern, Children's Medical Center

Dallas, Texas, 75235, United States

Location

MeSH Terms

Conditions

Heart Arrest; Diabetes Insipidus

Interventions

Vasopressins; Epinephrine

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Pituitary Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Biogenic Monoamines; Biogenic Amines; Catecholamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Tia Tortoriello Raymond, M.D.

  Universtiy of Texas Southwestern

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 24, 2008
• First Posted: March 5, 2008
• Study Start: April 1, 2008
• Primary Completion: October 1, 2010
• Study Completion: October 1, 2010
• Last Updated: September 17, 2019

Record last verified: 2019-09

Locations

US (1)