Low-dose Epinephrine Infusion Tests in Adolescent and Pediatric Patients (LEAP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00548886
Recruitment Status : Terminated (Lack of enrollment)
First Posted : October 24, 2007
Results First Posted : March 6, 2015
Last Update Posted : December 6, 2017
Children's Healthcare of Atlanta
Information provided by (Responsible Party):
Peter Fischbach, Emory University

Brief Summary:

Long QT syndrome (LQTS)is a cardiac disorder that may lead to ventricular arrythmias and culminate in syncope and/or possible death.

Recently, researchers have developed a way of discovering patients with LQTS by using low doses of epinephrine by a continuous, intravenous infusion in adults. Epinephrine, or adrenaline, is produced by our bodies in times of stress. By producing adrenaline, your body allows itself to adapt to its stressful environment and take appropriate actions (i.e. fight or flight response). By simulating this response with very small amounts of epinephrine, researchers have shown prolongation of the QT interval does not occur in normal healthy adults. However, adults with confirmed LQTS Type 1 (LQTS-1) will prolong their QT interval when given low dose epinephrine. Therefore, this test can act as a safe means of identifying adults with LQTS-1 who do not have prolonged QT intervals on their resting EKGs.

However, LQTS is not just a disease of adults, it affects children as well. Currently the standard of care is to obtain resting EKGs on our pediatric patients which can miss those patients with concealed LQTS. Those patients, who are old enough, can undergo exercise testing. Yet this leaves young children unable to run on a treadmill without a diagnostic test.

Hypothesis: The low-dose epinephrine infusion stress test does not cause prolongation of the QT interval in an electrophysiologically normal healthy pediatric population.

Condition or disease Intervention/treatment Phase
Congenital Disorders Drug: Epinephrine Not Applicable

Detailed Description:

This study will involve asking fifty children coming to the hospital for their standard of care procedure to treat a separate cardiac condition to participate. Patients approached will already have an intravenous line in place for their procedure. After consent and assent as necessary are obtained, the patient be brought to a separate room for the low-dose epinephrine infusion trial. The patient will lie down on a table, be hooked up to an EKG machine and the infusion will start. The amount of epinephrine actually infused is based on the weight of the patient but is substantially less than the dose received from an epinephrine auto-injection for anaphylaxis. After about 40 minutes, the trial will be completed and the patient may return to the waiting room for their original procedure. We have performed this test on a number of pediatric patients suspected of having LQTS with promising results and with little to no side effects. The patient will be awake for the procedure and will be able to verbalize concerns or complaints. A pediatric electrophysiologist and nurse will be present throughout the entire procedure.

The purpose of this study is to determine if children who are infused with low amounts of epinephrine will also maintain their normal QT interval as it does with healthy adults. This study would hope to prove that low-dose epinephrine infusion trials can serve as a way of identifying children with LQTS so that they may be effectively treated and potentially have their lives saved.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 7 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Health Services Research
Official Title: Low-dose Epinephrine Infusion Tests in Adolescent and Pediatric Patients
Study Start Date : February 2008
Actual Primary Completion Date : January 2012
Actual Study Completion Date : June 2012

Arm Intervention/treatment
Experimental: Epinephrine
Healthy pediatric subjects will receive epinephrine. Epinephrine infusion will begin at 0.025 ug/kg/minute, for ten minutes.The epinephrine infusion will then be increased to 0.05 ug/kg/minute for five minutes. The epinephrine infusion will then be increased to a maximal dose of 0.1 ug/kg/minute for five minutes. The epinephrine infusion is then discontinued.
Drug: Epinephrine
We will follow the protocol outlined by Ackerman et al. known as the Mayo protocol4 which is currently used routinely in our electrophysiology laboratory. Epinephrine infusion will begin at 0.025 ug/kg/minute, for ten minutes and a twelve-lead electrocardiogram is obtained at time=0 minutes, 5 minutes, and 10 minutes. The epinephrine infusion will then be increased to 0.05 ug/kg/minute for five minutes and the electrocardiogram repeated. The epinephrine infusion will then be increased to a maximal dose of 0.1 ug/kg/minute for five minutes and electrocardiogram obtained. The epinephrine infusion is then discontinued and measurements are obtained at five minutes and ten minutes after stopping the epinephrine infusion. The total time of procedure will be 35 minutes.
Other Name: adrenaline

Primary Outcome Measures :
  1. Percentage of Subjects With a Positive Result in Absolute QT Interval [ Time Frame: 35 minutes ]
    QT interval refers to the time interval on the standard electrocardiogram from the beginning of the QRS complex to the end of the T wave. Each participant had four QT intervals measured at each timepoint and the average was calculated for each patient at each timepoint for an absolute QT interval. Lengthening of the absolute QT interval greater than 30 milliseconds on low dose epinephrine infusion would be considered a positive result.

Secondary Outcome Measures :
  1. Determine Interobserver Variability When Measuring QT Intervals [ Time Frame: During enrollment period ]
    Two pediatric electrophysiologists were given photocopies of rhythm strips obtained from the electrocardiograms and the electrophysiologists will then take four separate measurements of the QT interval from each rhythm strip. Interobserver variability was measured between the two electrophysiologists and their measurements on the same rhythm strip. False positive results will be based on measurement error.

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Ages Eligible for Study:   3 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Patients ages 3-18 years
  2. Patients undergoing device closure of an atrial septal defect in the cardiac catheterization lab
  3. normal electrocardiogram without prolonged absolute or corrected QT interval(less than 440 msec)

Exclusion Criteria:

  1. Patients with a history of any other structural or acquired heart disease besides the atrial septal defect.
  2. Patient with a family history of sudden cardiac death, or personal history of syncope.
  3. Patient on alpha or beta-blocking medications.
  4. Pregnancy.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00548886

United States, Georgia
Children's Healthcare of Atlanta
Atlanta, Georgia, United States, 30322
Sponsors and Collaborators
Emory University
Children's Healthcare of Atlanta
Principal Investigator: Peter Fischbach, MD, MA Emory University

Responsible Party: Peter Fischbach, Associate Professor, Emory University Identifier: NCT00548886     History of Changes
Other Study ID Numbers: IRB00008105
First Posted: October 24, 2007    Key Record Dates
Results First Posted: March 6, 2015
Last Update Posted: December 6, 2017
Last Verified: November 2017

Keywords provided by Peter Fischbach, Emory University:
QT Prolongation
QT Interval
Stress test

Additional relevant MeSH terms:
Epinephryl borate
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
Vasoconstrictor Agents