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

NCT ID: NCT02885948

Last Updated: 2017-12-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 96 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-04-30
• Study Completion Date: 2017-12-31

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.

Conditions

Respiratory Depression

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Naloxone

Intervention Type: DRUG

used to block the effects of opioids, especially in overdose

Saline

The placebo arm of the study will receive an infusion of normal saline at a rate of 0.25ml/kg/hr.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo, ineffective control arm

Interventions

Naloxone

used to block the effects of opioids, especially in overdose

Intervention Type: DRUG

Placebo

Placebo, ineffective control arm

Intervention Type: DRUG

Other Intervention Names

Placebo Saline

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University College Dublin

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Peter Doran, PhD

Role: STUDY_DIRECTOR

UCD

Locations

Prof. Alistair Nichol

Dublin, , Ireland

Countries

Ireland

References

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.

Reference Type: DERIVED

PMID: 31792949 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29284510 (View on PubMed)

Other Identifiers

UCDCRC/15/006

Identifier Type: -

Identifier Source: org_study_id