Optimal Dose of Prophylactic Naloxone in Reducing Opioid-Induced Side Effects in Children/Adolescents
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Naloxone continuous infusion of naloxone administered in escalating dosing from 0.05 mcg/kg/hr to 1.65 mcg/kg/hour |
Drug: naloxone
continuous infusion of naloxone administered in escalating dosing from 0.05 mcg/kg/hr to 1.65 mcg/kg/hour
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Naloxone Side Effects [0-48 hours after infusion begins]
incidence of nausea, vomiting, pruritus following naloxone infusion
Eligibility Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | John Hopkins Hospital | Baltimore | Maryland | United States | 21287 |
Sponsors and Collaborators
- Johns Hopkins University
Investigators
- Principal Investigator: Myron Yaster, MD, Johns Hopkins University
Study Documents (Full-Text)
None provided.More Information
Publications
- 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.
- 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.
- 04-03-31-02
Study Results
Participant Flow
| Recruitment Details | 75 participants were consented, but only 64 participants participated in this study and were placed in the experimental arm. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Naloxone |
|---|---|
| Arm/Group Description | |
| Period Title: Overall Study | |
| STARTED | 64 |
| COMPLETED | 59 |
| NOT COMPLETED | 5 |
Baseline Characteristics
| Arm/Group Title | Group 1 |
|---|---|
| Arm/Group Description | |
| Overall Participants | 64 |
| Age (Count of Participants) | |
| <=18 years |
64
100%
|
| Between 18 and 65 years |
0
0%
|
| >=65 years |
0
0%
|
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
12
(6)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
32
50%
|
| Male |
32
50%
|
| Region of Enrollment (Count of Participants) | |
| United States |
64
100%
|
Outcome Measures
| Title | Number of Participants With Naloxone Side Effects |
|---|---|
| Description | incidence of nausea, vomiting, pruritus following naloxone infusion |
| Time Frame | 0-48 hours after infusion begins |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Naloxone |
|---|---|
| Arm/Group Description | |
| Measure Participants | 64 |
| Number (95% Confidence Interval) [participants] |
32
50%
|
Adverse Events
| Time Frame | ||
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Group 1 | |
| Arm/Group Description | ||
All Cause Mortality |
||
| Group 1 | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Group 1 | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/59 (0%) | |
Other (Not Including Serious) Adverse Events |
||
| Group 1 | ||
| Affected / at Risk (%) | # Events | |
| Total | 32/59 (54.2%) | |
| Gastrointestinal disorders | ||
| Nausea, Vomiting or pruritis | 32/59 (54.2%) | 59 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Myron Yaster |
|---|---|
| Organization | JHU |
| Phone | 9552393 |
| myaster1@jhmi.edu |
- 04-03-31-02