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

University College Dublin

Status and phase: Completed; Phase 4

Conditions: Respiratory Depression

Treatments: Drug: Naloxone; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT02885948

UCDCRC/15/006

Details and patient eligibility

About

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

Full 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.

Enrollment: 96 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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96 participants in 2 patient groups, including a placebo group

Naloxone

Experimental group

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.

Treatment:

Drug: Naloxone

Saline

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo