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

Study Overview
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Brief Summary
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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.

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

Conditions
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Overdose, Drug Abuse

Intervention / Treatment
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* Drug: Naloxone, intranasal
* Drug: placebo, intranasal
* Drug: Naloxone, intramuscular
* Drug: placebo, intramuscular


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double blinded, double dummy, randomized controlled trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Naloxone, intranasal<br> | Drug: Naloxone, intranasal<br>* 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.<br>|
| Active Comparator: Naloxone, intramuscular<br> | Drug: Naloxone, intramuscular<br>* 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<br>|
| Placebo Comparator: placebo, intranasal<br> | Drug: placebo, intranasal<br>* 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.<br>|
| Placebo Comparator: placebo, intramuscular<br> | Drug: placebo, intramuscular<br>* Intramuscular Sodium Chloride Injection 9mg/ml, will be administered as a 2 ml intramuscular injection in the deltoid muscle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | aspiration, cardiac arrest, death | The time participants are in the care of ambulance personnel, estimated 40 minutes | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Naloxone, Administration, Intranasal, Injections, Intramuscular, Narcotic Antagonists