NINA-1: Naloxone Nasal Spray Compared With Naloxone Injection for Opioid Overdoses Outside the Hospital

Sponsor

Norwegian University of Science and Technology (Other)

Overall Status

Completed

CT.gov ID

NCT03518021

Collaborator

St. Olavs Hospital (Other), Oslo University Hospital (Other)

286

Enrollment

Locations

Arms

28.7

Actual Duration (Months)

143

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Overdose Drug Abuse	Drug: Naloxone, intranasal Drug: placebo, intranasal Drug: Naloxone, intramuscular Drug: placebo, intramuscular	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

286 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Double blinded, double dummy, randomized controlled trialDouble blinded, double dummy, randomized controlled trial

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

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.

Primary Purpose:

Treatment

Official Title:

NTNU Intranasal Naloxone Trial - a Double Blinded, Double Dummy, Randomized Controlled Trial of Intranasal Naloxone for Pre-hospital Use

Actual Study Start Date :

May 15, 2018

Actual Primary Completion Date :

Oct 6, 2020

Actual Study Completion Date :

Oct 6, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Naloxone, intranasal	Drug: Naloxone, intranasal Active compound naloxone 14 mg/ml, (±10%). Nasal spray will be administered with one puff (100 microL ±10%) in one nostril (1.4 mg dose) using the Aptar Unitdose device. The spray device should be inserted about 1 cm into a nostril, pointing towards the ipsilateral ear and the plunger pushed in a firm and gentle manner for the formulation to be sprayed into the nose. After the plunger is inserted the device is immediately removed from the nose and assisted ventilation continued.
Active Comparator: Naloxone, intramuscular	Drug: Naloxone, intramuscular Intramuscular comparator Naloxone Hydrochloride 0.4 mg/ml will be administered as a 2 ml intramuscular (IM) injection in the deltoid muscle, total dose of 0,8 mg naloxone IM
Placebo Comparator: placebo, intranasal	Drug: placebo, intranasal Same spray but without naloxone. Nasal spray will be administered with one puff (100 microL +/- 10%) in one nostril using the Aptar Unitdose device. The spray device should be inserted about 1 cm into a nostril, pointing towards the ipsilateral ear and the plunger pushed in a firm and gentle manner for the formulation to be sprayed into the nose. After the plunger is inserted the device is immediately removed from the nose and assisted ventilation continued.
Placebo Comparator: placebo, intramuscular	Drug: placebo, intramuscular Intramuscular Sodium Chloride Injection 9mg/ml, will be administered as a 2 ml intramuscular injection in the deltoid muscle

Outcome Measures

Primary Outcome Measures

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 [40 minutes]

Secondary Outcome Measures

Changes in Glasgow Coma Scale (GCS) in patients treated with study medicine for opioid overdose [The time participants are in the care of ambulance personnel, estimated 40 minutes]
Changes in oxygen saturation (SaO2) in patients treated with study medicine for opioid overdose [The time participants are in the care of ambulance personnel, estimated 40 minutes]
Overdose complications [The time participants are in the care of ambulance personnel, estimated 40 minutes]
aspiration, cardiac arrest, death
Time from administration of naloxone to respiration above or equal to 10 breaths per minute [The time participants are in the care of ambulance personnel, estimated 40 minutes]
Opioid withdrawal reaction to naloxone reversal [The time participants are in the care of ambulance personnel, estimated 40 minutes]
Suitability of spray device in pre-hospital setting [The time participants are in the care of ambulance personnel, estimated 40 minutes]
Adverse reactions to naloxone formulation [The time participants are in the care of ambulance personnel, estimated 40 minutes]
Need for rescue naloxone, dose and route of administration during study visit [The time participants are in the care of ambulance personnel, estimated 40 minutes]
Recurrence of opioid overdose/ need for further pre-hospital naloxone within 12 hours of inclusion [12 hours]
reasons not to give rescue naloxone to non-responders [The time participants are in the care of ambulance personnel, estimated 40 minutes]
follow-up after care [The time participants are in the care of ambulance personnel, estimated 40 minutes]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Reduced (below and equal to 8 breaths per minute) or absent spontaneous respiration
Miosis
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Oslo University Hospital, Prehospital devision	Oslo		Norway
2	St Olavs Hospital, Department for Emergency Medicine and Prehospital Services	Trondheim		Norway

Sponsors and Collaborators

Norwegian University of Science and Technology
St. Olavs Hospital
Oslo University Hospital

Investigators

Study Director: Øystein Risa, Norwegian University of Science and Technology
Principal Investigator: Arne K Skulberg, MD PhD, Norwegian University of Science and Technology