The Pharmacology and Hemodynamics of Dexmedetomidine in Children With Congenital Heart Disease

Atrial Septal Defect Clinical Trial

Official title:

The Pharmacology of Dexmedetomidine in Children With Congenital Heart Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00480740
• Other study ID #: IRB# 3908
• Status: Completed
• Phase: Phase 3
• First received: May 29, 2007
• Last updated: June 17, 2015
• Start date: December 2006
• Est. completion date: October 2011

Study information

• Verified date: June 2015
• Source: Children's Research Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to examine the pharmacokinetics, pharmacodynamics, and pharmacogenomics of dexmedetomidine in the following three pediatric patient populations: patients with bi-directional cavopulmonary anastomosis or a Fontan procedure, patients who have had a cardiac transplant, and patients with otherwise normal physiology who are undergoing closure of a patent ductus arteriosis or atrial septal defect.

Description:

While opioid analgesia is currently the mainstream for management of pain in the perioperative setting, it often leads to significant morbidity, including opioid tolerance and hyperalgesia. Looking at ways to decrease the need for opioids with the use of adjunct medications allows for the long-term goal of decreasing physiologic tolerance in children. This is especially relevant in the pediatric congenital heart population.

Dexmedetomidine is in a class of drugs known as alpha-2 agonists and is known to provide analgesia, attenuate opioid tolerance and inhibit the sympathetic stress response. While there are numerous published case studies of dexmedetomidine validating its effectiveness and safety, the pharmacologic and pharmacodynamic profile has not been established.

This study will examine the hemodynamics, pharmacokinetics, and pharmacogenomics of dexmedetomidine in patients with congenital heart disease. The dose-ranging effect of dexmedetomidine will also be investigated. The three groups being studied will be: patients with bi-directional cavopulmonary anastomosis or a Fontan procedure, patients who have had a cardiac transplant, and patients with otherwise normal physiology who are undergoing closure of a patent ductus arteriosis or atrial septal defect.

Comparison: Compare both invasive and noninvasive hemodynamic parameters at baseline sevoflurane and during maintenance dosing on dexmedetomidine. The pharmacokinetics of dexmedetomidine in the pediatric population following escalating loading doses and continuous infusion at timed intervals will be estimated. The efficacy of dexmedetomidine will be estimated by the amount of rescue doses of propofol that are given.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: October 2011
• Est. primary completion date: October 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 18 Years

Eligibility

Inclusion Criteria:

• age is birth to 18 years

• > or = 6 kg.

• American Society of Anesthesiology (ASA) I, II, or III

• undergone prior cardiac transplant, Fontan or has a patent ductus arterious or atrial septal defect.

• scheduled for cardiac catheterization

Exclusion Criteria:

• subject or family history of malignant hyperthermia

• known hepatic disorder determined by history physical exam or laboratory tests

• pregnant or lactating female

• receiving inotropic agents or has a pacemaker

• weighs less than 6 kg.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Atrial Septal Defect
• Bidirectional Cavopulmonary Anastomosis
• Cardiac Transplant
• Heart Defects, Congenital
• Heart Diseases
• Heart Septal Defects
• Heart Septal Defects, Atrial
• Patent Ductus Arterious

Intervention

Drug:
• Dexmedetomidine
Dexmedetomidine load of 1 microgram/kilogram over 10 minutes, followed by a 1 microgram/kilogram/hour infusion during the time of catheterization

Locations

Country	Name	City	State
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Children's Research Institute

Country where clinical trial is conducted

United States, 

References & Publications (2)

Finkel JC, Elrefai A. The use of dexmedetomidine to facilitate opioid and benzodiazepine detoxification in an infant. Anesth Analg. 2004 Jun;98(6):1658-9, table of contents. — View Citation

Finkel JC, Johnson YJ, Quezado ZM. The use of dexmedetomidine to facilitate acute discontinuation of opioids after cardiac transplantation in children. Crit Care Med. 2005 Sep;33(9):2110-2. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in Hemodynamic Variables Recorded During Administration of Sevoflurane + Dexmedetomidine.	Non-inferiority was shown when differences at steady-state (dexmedetomidine + sevoflurane) compared to baseline (sevoflurane alone) and its associated 95% confidence interval fell completely within the range of plus or minus 20%.The 95% confidence interval was normalized by subtracting the baseline values.; Bispectral Index: monitors electroencephalographic and electromyographic parameters to monitor the depth of anesthesia.	Up to 24 hours following cardiac catheterization	Yes