The Use of Low Dose Prophylactic Naloxone Infusion to Prevent Respiratory Depression With Intrathecal Morphine. (NAPRESSIM)
Primary Purpose
Respiratory Depression
Status
Completed
Phase
Phase 4
Locations
Ireland
Study Type
Interventional
Intervention
Naloxone
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Respiratory Depression
Eligibility Criteria
Inclusion Criteria:
- Subjects must be aged 18 years or above at baseline
- Diagnosed with any hepatobiliary condition requiring an elective major surgical resection under general anaesthetic.
- Subjects must be able and willing to give written informed consent and to comply with the requirements of this study protocol
Exclusion Criteria:
- Allergy/sensitivity to naloxone
- Female subjects who are pregnant or breast-feeding.
- Subjects who have received any other investigational agent within 2 months
- Subjects taking anticonvulsant medications for epilepsy
- Subjects who have a cardiac arrhythmia with an uncontrolled rate
- Subjects who have a history of chronic opioid use / chronic pain
- Any contraindication to intrathecal injection eg coagulopathy
- Documented history of obstructive sleep apnoea
- Treating clinician feels not in the patients best interests to be randomised
Sites / Locations
- Prof. Alistair Nichol
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Naloxone
Saline
Arm Description
The naloxone arm of the study will receive naloxone at a rate of 5mcg/kg/hr which equates to 0.25ml/kg/hr. Each 1 ml ampoule of solution contains 400 micrograms (0.4mg) naloxone hydrochloride present as naloxone hydrochloride dihydrate. Excipients: each 1ml contains 3.55mg sodium. This will be diluted to a concentration of 20mcg/ml with 0.9% NaCl. Presented as solution for injection or infusion. Clear colourless sterile solution.
The placebo arm of the study will receive an infusion of normal saline at a rate of 0.25ml/kg/hr.
Outcomes
Primary Outcome Measures
Respiratory depression
Secondary Outcome Measures
Measure of occurrence of pain
Requirement for rescue analgesia
Nausea/Vomiting
Pruritus
Full Information
NCT ID
NCT02885948
First Posted
July 4, 2016
Last Updated
December 17, 2017
Sponsor
University College Dublin
1. Study Identification
Unique Protocol Identification Number
NCT02885948
Brief Title
The Use of Low Dose Prophylactic Naloxone Infusion to Prevent Respiratory Depression With Intrathecal Morphine.
Acronym
NAPRESSIM
Official Title
The NAPRESSIM Trial. The Use of Low Dose Prophylactic Naloxone Infusion to Prevent Respiratory Depression With Intrathecal Morphine.
Study Type
Interventional
2. Study Status
Record Verification Date
December 2017
Overall Recruitment Status
Completed
Study Start Date
April 2016 (undefined)
Primary Completion Date
December 2017 (Actual)
Study Completion Date
December 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University College Dublin
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is an investigator led, randomised, double blind, placebo controlled, double arm comparator study.
Detailed Description
Delayed respiratory depression is a well-documented side effect associated with the use of intrathecal morphine. This respiratory depression has implications for patient safety and necessitates either the observation of the patient in a high dependency setting for at least 24 hours or the use of an alternative analgesic technique. Other associated side effects include pruritus, nausea and vomiting and sedation. Naloxone is the most effective treatment for these side effects. However, it is usually given as a reactive treatment when the side effect presents.
The hypothesis is that patients who are commenced on a naloxone infusion at low dose early after injection of intrathecal morphine will have a clinically significant reduction in incidence of these side effects. The primary endpoint is a reduction in respiratory depression.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Respiratory Depression
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
96 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Naloxone
Arm Type
Experimental
Arm Description
The naloxone arm of the study will receive naloxone at a rate of 5mcg/kg/hr which equates to 0.25ml/kg/hr. Each 1 ml ampoule of solution contains 400 micrograms (0.4mg) naloxone hydrochloride present as naloxone hydrochloride dihydrate.
Excipients: each 1ml contains 3.55mg sodium. This will be diluted to a concentration of 20mcg/ml with 0.9% NaCl. Presented as solution for injection or infusion. Clear colourless sterile solution.
Arm Title
Saline
Arm Type
Placebo Comparator
Arm Description
The placebo arm of the study will receive an infusion of normal saline at a rate of 0.25ml/kg/hr.
Intervention Type
Drug
Intervention Name(s)
Naloxone
Intervention Description
used to block the effects of opioids, especially in overdose
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Placebo Saline
Intervention Description
Placebo, ineffective control arm
Primary Outcome Measure Information:
Title
Respiratory depression
Time Frame
within 16 - 24 hours of participation
Secondary Outcome Measure Information:
Title
Measure of occurrence of pain
Time Frame
within 16 - 24 hours of participation
Title
Requirement for rescue analgesia
Time Frame
within 16 - 24 hours of participation
Title
Nausea/Vomiting
Time Frame
within 16 - 24 hours of participation
Title
Pruritus
Time Frame
within 16 - 24 hours of participation
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subjects must be aged 18 years or above at baseline
Diagnosed with any hepatobiliary condition requiring an elective major surgical resection under general anaesthetic.
Subjects must be able and willing to give written informed consent and to comply with the requirements of this study protocol
Exclusion Criteria:
Allergy/sensitivity to naloxone
Female subjects who are pregnant or breast-feeding.
Subjects who have received any other investigational agent within 2 months
Subjects taking anticonvulsant medications for epilepsy
Subjects who have a cardiac arrhythmia with an uncontrolled rate
Subjects who have a history of chronic opioid use / chronic pain
Any contraindication to intrathecal injection eg coagulopathy
Documented history of obstructive sleep apnoea
Treating clinician feels not in the patients best interests to be randomised
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter Doran, PhD
Organizational Affiliation
UCD
Official's Role
Study Director
Facility Information:
Facility Name
Prof. Alistair Nichol
City
Dublin
ZIP/Postal Code
Dublin 4
Country
Ireland
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
31792949
Citation
Cosgrave D, Vencken S, Galligan M, McGuinness S, Soukhin E, McMullan V, Nair S, Puttappa A, Boylan J, Hussain R, Conlon N, Doran P, Nichol A. The effect of a low-dose naloxone infusion on the incidence of respiratory depression after intrathecal morphine administration for major open hepatobiliary surgery: a randomised controlled trial. Anaesthesia. 2020 Jun;75(6):747-755. doi: 10.1111/anae.14931. Epub 2019 Dec 2.
Results Reference
derived
PubMed Identifier
29284510
Citation
Cosgrave D, Galligan M, Soukhin E, McMullan V, McGuinness S, Puttappa A, Conlon N, Boylan J, Hussain R, Doran P, Nichol A. The NAPRESSIM trial: the use of low-dose, prophylactic naloxone infusion to prevent respiratory depression with intrathecally administered morphine in elective hepatobiliary surgery: a study protocol and statistical analysis plan for a randomised controlled trial. Trials. 2017 Dec 29;18(1):633. doi: 10.1186/s13063-017-2370-0.
Results Reference
derived
Learn more about this trial
The Use of Low Dose Prophylactic Naloxone Infusion to Prevent Respiratory Depression With Intrathecal Morphine.
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