Naloxone Nasal Spray Compared With Naloxone Injection for Opioid Overdoses Outside the Hospital

Drug Abuse Clinical Trial

— NINA-1  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03518021
• Other study ID #: 2016-004072-22
• Secondary ID: 2016/20002016-00
• Status: Completed
• Phase: Phase 3
• Start date: May 15, 2018
• Est. completion date: October 6, 2020

Study information

• Verified date: October 2020
• Source: Norwegian University of Science and Technology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 286
• Est. completion date: October 6, 2020
• Est. primary completion date: October 6, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Drug Abuse
• Drug Overdose
• Overdose
• Substance-Related Disorders

Intervention

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.
• 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.
• 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, intramuscular
Intramuscular Sodium Chloride Injection 9mg/ml, will be administered as a 2 ml intramuscular injection in the deltoid muscle

Locations

Country	Name	City	State
Norway	Oslo University Hospital, Prehospital devision	Oslo
Norway	St Olavs Hospital, Department for Emergency Medicine and Prehospital Services	Trondheim

Sponsors (3)

Lead Sponsor	Collaborator
Norwegian University of Science and Technology	Oslo University Hospital, St. Olavs Hospital

Country where clinical trial is conducted

Norway, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Overdose complications	aspiration, cardiac arrest, death	The time participants are in the care of ambulance personnel, estimated 40 minutes
Secondary	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
Secondary	Opioid withdrawal reaction to naloxone reversal		The time participants are in the care of ambulance personnel, estimated 40 minutes
Secondary	Suitability of spray device in pre-hospital setting		The time participants are in the care of ambulance personnel, estimated 40 minutes
Secondary	Adverse reactions to naloxone formulation		The time participants are in the care of ambulance personnel, estimated 40 minutes
Secondary	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
Secondary	Recurrence of opioid overdose/ need for further pre-hospital naloxone within 12 hours of inclusion		12 hours
Secondary	reasons not to give rescue naloxone to non-responders		The time participants are in the care of ambulance personnel, estimated 40 minutes
Secondary	follow-up after care		The time participants are in the care of ambulance personnel, estimated 40 minutes