This section contains study documents forming the basis of the NINA-1 Trial.

Documents will be added at Sponsors discretion, and aim to reflect the Trial Master File. Please consult the file 00readme for a key to how documents are coded in this dataset.

If you have any specific document you would like access to, please contact us, and Sponsor will consider publication.

Some documents will be altered to facilitate open publication. In such case this will be clearly marked.

All documents are combined with approved translations into English and original document in Norwegian where necessary.

The NINA-1 Trial is a phase 3 drugs trial of nasal naloxone. It is double-blinded, double dummy, randomised controlled trial, two-centre study, non-inferiority design. The centres are Oslo University Hospital and St Olav’s Hospital, University Hospital of Trondheim. As we compare two different routes of administration, a dummy design is needed to blind the ambulance crew for the intervention. This means patients will receive a nasal spray and an intramuscular injection simultaneously, randomised for one to contain the antidote naloxone, the other inactive sterile saline solution. It is designed and powered to be a non-inferiority study with an estimated 200 participants to be included.

The primary endpoint is the proportion of participants with return of spontaneous respiration (≥10 breaths per minute) within 10 minutes of naloxone administration. The aim is to demonstrate that intranasal administration of naloxone is not clinically inferior to intramuscular administration. It is expected that 88% of the patients on IM treatment will be responders and an equivalent dose intranasal administration is expected to result in a similar responder rate. The non-inferiority margin is set at Δ=0.15. The null hypothesis is that the proportion of responders given intranasal naloxone is smaller than given intramuscular naloxone.