Clinical trial NCT00330343: Optimal Dose of Prophylactic Naloxone in Reducing Opioid-Induced Side Effects in Children/Adolescents
Official title: The Optimal Dose of Prophylactic Naloxone in Ameliorating Opioid Induced Side Effects in Children and Adolescents Receiving Intravenous Patient Controlled Analgesia (IVPCA) Morphine for Moderate to Severe Pain: A Pharmacodynamic, Pharmacokinetic, and Pharmacogenetic Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pain
Nausea
Pruritus
Keywords: morphine
naloxone
pediatrics
adverse effects
pain
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
First posted: 2006-05-26
Enrollment: 75
Sex: ALL
Minimum age (years): 7
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Participants With Naloxone Side Effects
timeFrame: 0-48 hours after infusion begins
Secondary outcomes:
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: John Hopkins Hospital
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Myron Yaster, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.