Drug Abuse, Overdose
Conditions
Keywords
Naloxone, Administration, Intranasal, Injections, Intramuscular, Narcotic Antagonists
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.
Interventions
DRUGNaloxone, 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.
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.
DRUGNaloxone, 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
DRUGplacebo, intramuscular
Intramuscular Sodium Chloride Injection 9mg/ml, will be administered as a 2 ml intramuscular injection in the deltoid muscle
Sponsors
St. Olavs Hospital
Oslo University Hospital
Norwegian University of Science and Technology
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, 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.
Intervention model description
Double blinded, double dummy, randomized controlled trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| 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 | — |
| 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 | — |
| Adverse reactions to naloxone formulation | The time participants are in the care of ambulance personnel, estimated 40 minutes | — |
Countries
Norway
Outcome results
None listed