Clinical trial NCT02885948: The Use of Low Dose Prophylactic Naloxone Infusion to Prevent Respiratory Depression With Intrathecal Morphine.
Official title: The NAPRESSIM Trial. The Use of Low Dose Prophylactic Naloxone Infusion to Prevent Respiratory Depression With Intrathecal Morphine.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Respiratory Depression
Lead sponsor: University College Dublin
Sponsor class: OTHER
First posted: 2016-09-01
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Respiratory depression
timeFrame: within 16 - 24 hours of participation
Secondary outcomes:
measure: Measure of occurrence of pain
timeFrame: within 16 - 24 hours of participation
measure: Requirement for rescue analgesia
timeFrame: within 16 - 24 hours of participation
measure: Nausea/Vomiting
timeFrame: within 16 - 24 hours of participation
measure: Pruritus
timeFrame: within 16 - 24 hours of participation
Other outcomes:
Locations:
city: Dublin
country: Ireland
facility: Prof. Alistair Nichol
Study officials:
affiliation: UCD
name: Peter Doran, PhD
role: STUDY_DIRECTOR
References:
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.
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.