Clinical trial NCT03518021: Naloxone Nasal Spray Compared With Naloxone Injection for Opioid Overdoses Outside the Hospital
Official title: NTNU Intranasal Naloxone Trial - a Double Blinded, Double Dummy, Randomized Controlled Trial of Intranasal Naloxone for Pre-hospital Use
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Overdose
Drug Abuse
Keywords: Naloxone
Administration, Intranasal
Injections, Intramuscular
Narcotic Antagonists
Lead sponsor: Norwegian University of Science and Technology
Sponsor class: OTHER
Collaborators: name: St. Olavs Hospital
name: Oslo University Hospital
First posted: 2018-05-08
Enrollment: 286
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double blinded, double dummy, randomized controlled trial
Primary purpose: TREATMENT

Brief summary: This trial will compare the clinical response to intramuscular and intranasal naloxone in pre-hospital opioid overdoses. Objective of the study is to measure and evaluate clinical response (return of spontaneous respiration within 10 minutes of naloxone administration) to a new nasal naloxone formulation in real opioid overdoses in the pre-hospital environment. The aim is to demonstrate that intranasal administration of naloxone is not clinically inferior to intramuscular administration, which is now standard treatment of care.


Eligibility criteria: Inclusion Criteria:

* Suspected opioid overdose clinically diagnosed by emergency medical service (EMS) based on the following criteria

  1. Reduced (below and equal to 8 breaths per minute) or absent spontaneous respiration
  2. Miosis
  3. Glasgow Coma Scale (GCS) below 12
* Palpable carotid or radial arterial pulse

Exclusion Criteria:

* Cardiac arrest
* Failure to assist ventilation using mask-bag technique
* Facial trauma or epistaxis or visible nasal blockage
* Iatrogenic opioid overdose when opioid is administered in- hospital, or by EMS or other health care workers in the pre- hospital setting
* Suspected or visibly pregnant participant
* Has received naloxone by any route in the current overdose
* in prison or custody by police
* EMS staff without training as study workers
* No study drug available
* Study drug frozen as indicated by Freeze Watch in kit or past its expiry date
* Deemed unfit for inclusion due to any other cause by study personnel at the scene; such as unsafe work environment for EMS

Primary outcomes:
measure: Proportion of patients with return of spontaneous respiration (above or equal to 10 breaths per minute) within 10 minutes of naloxone administration in pre-hospital opioid overdose
timeFrame: 40 minutes
Secondary outcomes:
measure: Changes in Glasgow Coma Scale (GCS) in patients treated with study medicine for opioid overdose
timeFrame: The time participants are in the care of ambulance personnel, estimated 40 minutes
measure: Changes in oxygen saturation (SaO2) in patients treated with study medicine for opioid overdose
timeFrame: The time participants are in the care of ambulance personnel, estimated 40 minutes
measure: Overdose complications
timeFrame: The time participants are in the care of ambulance personnel, estimated 40 minutes
measure: Time from administration of naloxone to respiration above or equal to 10 breaths per minute
timeFrame: The time participants are in the care of ambulance personnel, estimated 40 minutes
measure: Opioid withdrawal reaction to naloxone reversal
timeFrame: The time participants are in the care of ambulance personnel, estimated 40 minutes
measure: Suitability of spray device in pre-hospital setting
timeFrame: The time participants are in the care of ambulance personnel, estimated 40 minutes
measure: Adverse reactions to naloxone formulation
timeFrame: The time participants are in the care of ambulance personnel, estimated 40 minutes
measure: Need for rescue naloxone, dose and route of administration during study visit
timeFrame: The time participants are in the care of ambulance personnel, estimated 40 minutes
measure: Recurrence of opioid overdose/ need for further pre-hospital naloxone within 12 hours of inclusion
timeFrame: 12 hours
measure: reasons not to give rescue naloxone to non-responders
timeFrame: The time participants are in the care of ambulance personnel, estimated 40 minutes
measure: follow-up after care
timeFrame: The time participants are in the care of ambulance personnel, estimated 40 minutes
Other outcomes:
Locations:
city: Oslo
country: Norway
facility: Oslo University Hospital, Prehospital devision
city: Trondheim
country: Norway
facility: St Olavs Hospital, Department for Emergency Medicine and Prehospital Services
Study officials:
affiliation: Norwegian University of Science and Technology
name: Øystein Risa
role: STUDY_DIRECTOR
affiliation: Norwegian University of Science and Technology
name: Arne K Skulberg, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Skulberg AK, Tylleskar I, Braarud AC, Dale J, Heyerdahl F, Mellesmo S, Valberg M, Dale O. NTNU intranasal naloxone trial (NINA-1) study protocol for a double-blind, double-dummy, non-inferiority randomised controlled trial comparing intranasal 1.4 mg to intramuscular 0.8 mg naloxone for prehospital use. BMJ Open. 2020 Nov 12;10(11):e041556. doi: 10.1136/bmjopen-2020-041556.