Naloxone for the Treatment of Opioid-Induced Pruritus

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by University of British Columbia
Sponsor:
Information provided by (Responsible Party):
University of British Columbia
ClinicalTrials.gov Identifier:
NCT01071057
First received: February 17, 2010
Last updated: August 29, 2014
Last verified: August 2014
  Purpose

The purpose of this study is to improve how we treat itching, a common side effect associated with the use of morphine pain medication. Itching is a problem experienced by up to 30% of the children treated with pain medications in the morphine family.

Despite studies demonstrating the effectiveness of using naloxone to treat itchiness in adults receiving morphine pain medications, there are not many studies in children. This study is designed to study how well naloxone works for treatment of itching in children


Condition Intervention Phase
Pruritus
Drug: Naloxone
Drug: Saline/Morphine
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: Naloxone for the Treatment of Opioid-Induced Pruritus: A Double-Blind, Prospective, Randomized, Controlled Study

Resource links provided by NLM:


Further study details as provided by University of British Columbia:

Primary Outcome Measures:
  • Pruritus incidence and intensity [ Time Frame: 2 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Self-report pain scores [ Time Frame: 2 days ] [ Designated as safety issue: No ]
  • Morphine, ondansetron, diphenhydramine utilization [ Time Frame: 2 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 85
Study Start Date: December 2010
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Naloxone/morphine
Naloxone (12 µg/ml) mixed in a single infusion with morphine (1 mg/ml). The study solutions will be prepared by a pharmacist and diluted in saline to produce equal volumes to ensure proper blinding.
Drug: Naloxone
Basal infusion of 20µg/kg/hour, bolus dose of 20µg /kg, lockout of 5 minutes with hourly maximum not to exceed 150µg /kg/hr, maximum 6 bolus doses. Subject pain relief will be assessed and documented by nursing staff and supervised by the Acute Pain Service (APS). Morphine will be titrated to subject need according to APS PCA protocol.
Placebo Comparator: saline/morphine
Patients will be randomly assigned to one of two groups (Naloxone/morphine or saline/morphine) using computer-generated random numbers. On arrival to the PACU patients will be started on IV PCA and randomized study drug
Drug: Saline/Morphine
Basal infusion of 20µg/kg/hour, bolus dose of 20µg /kg, lockout of 5 minutes with hourly maximum not to exceed 150µg /kg/hr, maximum 6 bolus doses. Subject pain relief will be assessed and documented by nursing staff and supervised by the Acute Pain Service (APS). Morphine will be titrated to subject need according to APS PCA protocol.

Detailed Description:

Hypothesis: Naloxone co-administered simultaneously with standard Patient Controlled Analgesia (PCA) basal and bolus morphine will significantly reduce the incidence of Opioid Induced Pruritus (OIP) without affecting analgesia or opioid consumption in children.

Specific Objectives:

  1. To determine if naloxone (12 µg/ml) mixed in a single infusion with morphine (1 mg/ml) will be effective in the prevention of opioid induced pruritus (OIP).
  2. To determine if treatment with naloxone will result in attenuation of analgesia or an increase in opioid utilisation.
  3. To determine if treatment with naloxone will reduce other opioid induced side effects such as nausea and vomiting.

Methods: This study is divided into two phases. Phase 1 - Although, there are studies confirming the compatibility of morphine (4 mg/mL) with naloxone (16 µg/mL) in separate infusion pumps run into the same intravenous site, there are no studies confirming the chemical and physical compatibility of morphine and naloxone in the same syringe with the standard concentrations used at BCCH. Therefore, a compatibility and stability study of naloxone and morphine solution in the same syringe will be performed.

Phase 2 - Phase 2 is a blinded clinical trial where 70 subjects will be randomized to receive either morphine mixed with naloxone or morphine mixed with placebo.With institutional review board approval, and written parental/guardian informed consent (and assent if appropriate), we will recruit children, ages 5-16 years, receiving intravenous opioids via PCA for post-operative pain control. Subjects will be evaluated every 4 hr for pain scores, frequency of vomiting, nausea, pruritus, sedation, and respiratory depression. At 24 and 48 hr, the total morphine consumption will be calculated.

Data analysis: Differences in the incidence and intensity of pruritus between the two groups will be compared. We will review side effects using the following control variables: (1) demographic data; and (2) summation of opioid use in each 4 hr period for total opioid consumption. ANOVA and crosstabs will be used where appropriate to analyze data.

  Eligibility

Ages Eligible for Study:   5 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Children 5-18 years of age undergoing surgery at BCCH
  • ASA I - II.
  • Children receiving PCA morphine.
  • Informed consent/assent provided by child/parent/guardian.

Exclusion Criteria

  • Children with known abnormal developmental profile.
  • Children with known opioid allergy.
  • Inability/failure to obtain informed consent/assent from parent/guardian/child.
  • Children receiving concurrent opioids.
  • Children with pre-existing pruritus from non-opioid related cause.
  • Children receiving PCA hydromorphone or fentanyl.
  • ASA 3 and above.
  • Children who require admission to the Pediatric Intensive Care Unit (PICU). - Children involved in any investigational drug trial within the previous one month.
  • Any child in the study that experiences unmanageable pruritus within the protocol time frame and is converted to hydromorphone will continue to be monitored for 48 hours. However, this will be taken into account during statistical analysis of study results. Appropriate conventional rescue medication for pruritus (diphenhydramine 0.5mg/kg IV 4hrly PRN) will be provided for any child who continues to experience pruritus.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01071057

Contacts
Contact: Joanne Lim 604-875-2000 ext 6669 jlim2@cw.bc.ca

Locations
Canada, British Columbia
British Columbia Children's Hospital Department of Anesthesia Recruiting
Vancouver, British Columbia, Canada, V6H 3V4
Contact: Joanne Lim    604-875-2000 ext 6669    jlim2@cw.bc.ca   
Sponsors and Collaborators
University of British Columbia
Investigators
Principal Investigator: Gillian Lauder, Dr. University of British Columbia
Study Director: Roxane Carr, Dr. University of British Columbia
Study Director: Mark Ansermino, Dr. University of British Columbia
  More Information

No publications provided

Responsible Party: University of British Columbia
ClinicalTrials.gov Identifier: NCT01071057     History of Changes
Other Study ID Numbers: H09-03001
Study First Received: February 17, 2010
Last Updated: August 29, 2014
Health Authority: Canada: Health Canada

Keywords provided by University of British Columbia:
opioid-induced pruritus
naloxone

Additional relevant MeSH terms:
Pruritus
Signs and Symptoms
Skin Diseases
Skin Manifestations
Morphine
Naloxone
Analgesics
Analgesics, Opioid
Central Nervous System Agents
Central Nervous System Depressants
Narcotic Antagonists
Narcotics
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 30, 2014