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

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

This is an investigator led, randomised, double blind, placebo controlled, double arm comparator study.

Study Overview

• Status: Completed
• Conditions: Respiratory Depression
• Intervention / Treatment: Drug: Naloxone; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 4

Contacts and Locations

Study Locations

• Ireland
  • Dublin, Ireland, Dublin 4
    • Prof. Alistair Nichol

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: University College Dublin
• Investigators: Study Director: Peter Doran, PhD, UCD

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: April 1, 2016
• Primary Completion (Actual): December 1, 2017
• Study Completion (Actual): December 1, 2017

Study Registration Dates

• First Submitted: July 4, 2016
• First Submitted That Met QC Criteria: August 26, 2016
• First Posted (Estimate): September 1, 2016

Study Record Updates

• Last Update Posted (Actual): December 19, 2017
• Last Update Submitted That Met QC Criteria: December 17, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Respiratory Tract Diseases; Mood Disorders; Respiration Disorders; Depression; Depressive Disorder; Respiratory Insufficiency; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Narcotic Antagonists; Naloxone
• Other Study ID Numbers: UCDCRC/15/006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided