The Use of Low Dose Prophylactic Naloxone Infusion to Prevent Respiratory Depression With Intrathecal Morphine.

Study Overview
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Brief Summary
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This is an investigator led, randomised, double blind, placebo controlled, double arm comparator study.

Detailed Description
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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.

Official Title
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The NAPRESSIM Trial. The Use of Low Dose Prophylactic Naloxone Infusion to Prevent Respiratory Depression With Intrathecal Morphine.

Conditions
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Respiratory Depression

Intervention / Treatment
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* Drug: Naloxone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Naloxone<br>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. | Drug: Naloxone<br>* used to block the effects of opioids, especially in overdose<br>|
| Placebo Comparator: Saline<br>The placebo arm of the study will receive an infusion of normal saline at a rate of 0.25ml/kg/hr. | Drug: Placebo<br>* Placebo, ineffective control arm<br>* Other names: Placebo Saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Respiratory depression |  | within 16 - 24 hours of participation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure of occurrence of pain |  | within 16 - 24 hours of participation | 
| Requirement for rescue analgesia |  | within 16 - 24 hours of participation | 
| Nausea/Vomiting |  | within 16 - 24 hours of participation | 
| Pruritus |  | within 16 - 24 hours of participation |