Measuring the Amount of Methadone or Morphine in the Blood of Neonates, Infants & Children After Cardiac Surgery.

NCT01094522 | Completed Phase 1 Results

• 2 other identifiers: SU-03012010-5083IRB Protocol # 16739
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 3

Brief Summary

Study Population: Neonates, infants and children from birth to 5 years of age undergoing cardiac surgery with CPB. The use of methadone to provide analgesia may be increasing due to advantages compared to other commonly used opioid analgesic drugs. While efficacy of methadone has been reported in adults, there is a paucity of information in neonates and infants. In the latter population, fentanyl and morphine are most commonly used for opioid analgesia following major surgery, while methadone is frequently used for weaning of opioid dependent and tolerant patients, in spite of the paucity of knowledge of methadone pharmacology in this population. There are several clinical problems associated with fentanyl and morphine, and methadone may offer superior efficacy with fewer side effects than these agents. We propose to study the pharmacokinetics (PK) and pharmacodynamics (PD) of methadone in neonates and infants in the intensive care unit following cardiac surgery.

Conditions

Pain

Outcome Measures

Primary Outcomes (2)

• Maximum Concentration of Morphine Including Its Metabolites (Morphine-3-glucuronide and Morphine-6-glucuronide)

  0, 15, 30 minutes, 1, 2, 4, 6 hrs, every 6 hrs up to 24 hrs

• Maximum Concentration of Methadone Including Its Metabolites (EDDP and EMDP)

  0, 15, 30 minutes, 1, 2, 4, 6 hrs, every 6 hrs up to 24 hrs

Secondary Outcomes (2)

• •Pain Scores (FLACC) During the 24 Hours Study Period

  24 hours

• •Amount of Study Drug Administered During the 24-hour Dosing Period

  24 hours

Study Arms (2)

Methadone

EXPERIMENTAL

One half the Study patients will be randomized to receive a loading dose of IV methadone, followed by IV doses (given by the ICU nurse), on a PRN basis, for pain control for up to 24 hours during their postoperative course while they are intubated.

Drug: Methadone

Morphine

ACTIVE COMPARATOR

One half the Study patients will be randomized to receive a loading dose of IV morphine, followed by IV doses (given by the ICU nurse), on a PRN basis, for pain control for up to 24 hours during their postoperative course while they are intubated.

Drug: Morphine

Interventions

Methadone DRUG

0.2 mg/kg (IV) for the Initial Loading Dose; followed by PRN ("as needed") doses (given by the ICU Nurses) starting at 0.035 mg/kg (IV) every 30 minutes, for postoperative pain. The PRN dose of methadone may be increased by the ICU doctors until the dose is adequate to relieve the patient's pain.

Methadone

Morphine DRUG

0.2 mg/kg (IV) for the Initial Loading Dose; followed by PRN ("as needed") doses (given by the ICU Nurses) starting at 0.035 mg/kg (IV) every 30 minutes, for postoperative pain. The PRN dose of morphine may be increased by the ICU doctors until the dose is adequate to relieve the patient's pain.

Also known as: MS

Morphine

Eligibility Criteria

• Age: Up to 5 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Neonates, infants and children from birth through 5 years of age undergoing mechanical ventilation following cardiac surgery for congenital heart disease. Congenital heart lesions include "two ventricle repairs", including tetralogy of Fallot, transposition of the great arteries, "unobstructed" total anomalous pulmonary venous return, truncus arteriosus, atrioventricular canal defect and ventricular septal defect.

You may not qualify if:

• Subjects will be excluded from the study because of prematurity (gestational age \< 37 weeks), weight \< 3.0 kg, severe hepatic dysfunction (elevation of conjugated bilirubin \> 2, AST/ALT \> 200 IU/L), significant renal dysfunction (serum Cr \> 1.5 mg/dL), participation within 30 days of study entry or within 5 times the half-life, whichever is longer, in another investigational drug study, or previous participation in this study. Patients will be excluded if they have received opioids for more than 12 hours of the 48-hour period prior to surgery. In addition, patients will be excluded if they have a history of other clinically significant medical problems, which, in the opinion of the investigator, would interfere with study participation.

Sponsors & Collaborators

• Stanford University: lead
• University of Colorado, Denver: collaborator
• Oregon Health and Science University: collaborator

Study Sites (3)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

University of Colorado

Denver, Colorado, United States

Location

Oregon Health & Sciences University

Portland, Oregon, 97239, United States

Location

Related Publications (2)

• Ward RM, Drover DR, Hammer GB, Stemland CJ, Kern S, Tristani-Firouzi M, Lugo RA, Satterfield K, Anderson BJ. The pharmacokinetics of methadone and its metabolites in neonates, infants, and children. Paediatr Anaesth. 2014 Jun;24(6):591-601. doi: 10.1111/pan.12385. Epub 2014 Mar 26.

  PMID: 24666686 RESULT

• Elkomy MH, Drover DR, Glotzbach KL, Galinkin JL, Frymoyer A, Su F, Hammer GB. Pharmacokinetics of Morphine and Its Metabolites in Infants and Young Children After Congenital Heart Surgery. AAPS J. 2016 Jan;18(1):124-33. doi: 10.1208/s12248-015-9826-5. Epub 2015 Sep 9.

  PMID: 26349564 RESULT

MeSH Terms

Conditions

Pain

Interventions

Methadone; Morphine

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ketones; Organic Chemicals; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Results Point of Contact

• Title: Dr. Gregory Hammer
• Organization: Stanford University School of Medicine

ham@stanford.edu

6507367359

Study Officials

• Gregory Hammer

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Anesthesia and Pediatrics

Study Record Dates

• First Submitted: March 25, 2010
• First Posted: March 29, 2010
• Study Start: March 1, 2010
• Primary Completion: June 1, 2012
• Study Completion: June 1, 2012
• Last Updated: September 18, 2017
• Results First Posted: August 9, 2017

Record last verified: 2017-08

Locations

US (3)