Optimal Dose of Prophylactic Naloxone in Reducing Opioid-Induced Side Effects in Children/Adolescents

NCT ID: NCT00330343

Last Updated: 2017-07-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 75 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-05-31
• Study Completion Date: 2009-06-30

Brief Summary

This is an investigator initiated dose finding study designed to determine the optimal dose of naloxone to prevent or minimize the most common side effects induced by opioids, namely itching, nausea, and vomiting. Male and female inpatients of the Children's Center of the Johns Hopkins Hospital, who are greater than 6 and less than 18 years of age with acute, moderate to severe pain, and who are to be treated with intravenous Patient controlled analgesia (IVPCA) morphine will be eligible for inclusion in this study. Patients will be recruited by a study investigator prior to the initiation of IVPCA therapy. The majority of patients will be post operative patients, and will start therapy and the investigational drug in the Post Anesthesia Care Unit or the Pediatric Intensive Care Unit. The investigators plan on studying between 10 and 99, male and female patients over a 2 year period.

Detailed Description

In patients of all ages, opioids are the cornerstone of management of moderate to severe pain. Regardless of method of administration, all opioids produce unwanted side effects, including pruritus, nausea and vomiting, constipation, urinary retention, cognitive impairment, tolerance, dependence, and (rarely) respiratory depression. Based on the results of a previously completed randomized controlled trial, children and adolescents with moderate to severe pain, are now routinely treated in the Children's Center of the Johns Hopkins Hospital with a low dose naloxone infusion (0.25 mcg/kg/HOUR) whenever morphine intravenous patient controlled analgesia (IVPCA) or parent/nurse controlled analgesia (IVPNCA) is initiated. Although the previous study showed a marked reduction in the incidence and severity of pruritus and nausea, approximately a third of the patients still experience these side effects. The primary purpose of this study is to reduce this failure rate by determining if there is an optimal dose of naloxone to prevent opioid induced side effects as determined by a dose finding classic up down dose escalation method. The second aim is to determine the pharmacokinetics of morphine and naloxone and their metabolites at each of the naloxone infusion rates attempted. The investigators will measure morphine, naloxone, and their metabolites using a liquid chromatographic-electrospray ionization-tandem mass spectrometric method (LC/MS/MS). The final aim is to determine the pharmacogenetics of responders and non-responders using DNA isolated from patient blood. To accomplish this the investigators will need a single blood collection from patients currently being treated with IVPCA morphine and low dose intravenous naloxone.

Conditions

Pain; Nausea; Pruritus

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Naloxone

continuous infusion of naloxone administered in escalating dosing from 0.05 mcg/kg/hr to 1.65 mcg/kg/hour

Group Type: EXPERIMENTAL

naloxone

Intervention Type: DRUG

continuous infusion of naloxone administered in escalating dosing from 0.05 mcg/kg/hr to 1.65 mcg/kg/hour

Interventions

naloxone

continuous infusion of naloxone administered in escalating dosing from 0.05 mcg/kg/hr to 1.65 mcg/kg/hour

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male and female patients greater than 6 and less than 18 years of age with acute, moderate to severe pain who are to start treatment with IVPCA morphine as inpatients of the Children's Center of the Johns Hopkins Hospital

Exclusion Criteria

• patients who require concomitant benzodiazepine administration
• allergic to opioids
• have been in an investigational drug trial within 1 month
• received opioids with in 7 days of the study
• parent with psychiatric illness which impairs their ability to provide consent parent who does not speak English

• Minimum Eligible Age: 7 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Johns Hopkins University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Myron Yaster, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

John Hopkins Hospital

Baltimore, Maryland, United States

Countries

United States

References

Maxwell LG, Kaufmann SC, Bitzer S, Jackson EV Jr, McGready J, Kost-Byerly S, Kozlowski L, Rothman SK, Yaster M. The effects of a small-dose naloxone infusion on opioid-induced side effects and analgesia in children and adolescents treated with intravenous patient-controlled analgesia: a double-blind, prospective, randomized, controlled study. Anesth Analg. 2005 Apr;100(4):953-958. doi: 10.1213/01.ANE.0000148618.17736.3C.

Reference Type: BACKGROUND

PMID: 15781505 (View on PubMed)

Gan TJ, Ginsberg B, Glass PS, Fortney J, Jhaveri R, Perno R. Opioid-sparing effects of a low-dose infusion of naloxone in patient-administered morphine sulfate. Anesthesiology. 1997 Nov;87(5):1075-81. doi: 10.1097/00000542-199711000-00011.

Reference Type: BACKGROUND

PMID: 9366459 (View on PubMed)

Other Identifiers

04-03-31-02

Identifier Type: -

Identifier Source: org_study_id