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.

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

NTNU has complete ownership and publishing rights of all results, regardless of outcome. The full protocol, Statistical Analysis Plan, information letter for consent and other trial documents will be published open access in the NTNU Open repository. The Clinical Study report and Statistical Analysis Report will also be made openly available, but open versions may be censored to ensure that it will not be possible to identify individual study participants. The datasets analysed during the current study will be made available from NTNU upon reasonable request and a methodological sound proposal based on the consent given by participants.

Updated regularly, but no later than one year after publication of main results

NTNU will require data processor agreements for recipients conform to standards set out in Norwegian Law and the European General Data Protection Regulation. Any shared datasets will have pseudonymisation of personal data. If doubt NTNU will seek advice from Ethics Committee.

The whole study team, including the statistician, will be blinded until after database lock and the primary analysis are done. The allocation list will be stored by by the Hospital Pharmacy Trondheim. There will not be automatic unblinding of SAEs. Study personnel do not have any access to the allocation list. An emergency option for individual unblinding is available to medical monitor in case of SAE/ SUSAR Study workers are blinded to the different preparations. This is carefully performed by covering the vials with neutral and opaque labels for "study drug". The risk of for unintentional unblinding is very small. The procedure for securing credible blinding is described in the study protocol and approved by the Norwegian Medicines Agency.