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OverdosePhase 3NINA-1NCT03518021

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

A Phase 3 study testing Naloxone, intranasal and Naloxone, intramuscular in people with Overdose and Drug Abuse, run by Norwegian University of Science and Technology at 2 sites in Norway.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Overdose, Drug Abuse
What is being tested?
Naloxone, intranasal and Naloxone, intramuscular
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
286 participants
Where
2 sitesNorway
Study dates
15 May 2018to 6 Oct 2020
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 11Show fewer
  • 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

Trial locations and contacts

2 sites in 1 country.

Norway2 sites

  • Oslo University Hospital, Prehospital devision

    Oslo

  • St Olavs Hospital, Department for Emergency Medicine and Prehospital Services

    Trondheim

Other trials in Norway

About this study

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

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.

Conditions
Overdose, Drug Abuse
Being tested
Naloxone, intranasal, placebo, intranasal, Naloxone, intramuscular, placebo, intramuscular
Keywords
Naloxone, Administration, Intranasal, Injections, Intramuscular, Narcotic Antagonists
Medical subject headings
Drug Overdose, Substance-Related Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Naloxone, intranasalDrug

    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, intranasalDrug

    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, intramuscularDrug

    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, intramuscularDrug

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

Study groups in NCT03518021
Study groupRoleWhat they receive
Naloxone, intranasalExperimentalNot described
Receives: Drug: Naloxone, intranasal
Naloxone, intramuscularActive comparatorNot described
Receives: Drug: Naloxone, intramuscular
placebo, intranasalPlacebo comparatorNot described
Receives: Drug: placebo, intranasal
placebo, intramuscularPlacebo comparatorNot described
Receives: Drug: placebo, intramuscular

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 40 minutes

Secondary outcomes (11)

  1. Changes in Glasgow Coma Scale (GCS) in patients treated with study medicine for opioid overdose

    Measured: The time participants are in the care of ambulance personnel, estimated 40 minutes

  2. Changes in oxygen saturation (SaO2) in patients treated with study medicine for opioid overdose

    Measured: The time participants are in the care of ambulance personnel, estimated 40 minutes

  3. Overdose complications

    aspiration, cardiac arrest, death

    Measured: The time participants are in the care of ambulance personnel, estimated 40 minutes

  4. Time from administration of naloxone to respiration above or equal to 10 breaths per minute

    Measured: The time participants are in the care of ambulance personnel, estimated 40 minutes

  5. Opioid withdrawal reaction to naloxone reversal

    Measured: The time participants are in the care of ambulance personnel, estimated 40 minutes

  6. Suitability of spray device in pre-hospital setting

    Measured: The time participants are in the care of ambulance personnel, estimated 40 minutes

  7. Adverse reactions to naloxone formulation

    Measured: The time participants are in the care of ambulance personnel, estimated 40 minutes

  8. Need for rescue naloxone, dose and route of administration during study visit

    Measured: The time participants are in the care of ambulance personnel, estimated 40 minutes

  9. Recurrence of opioid overdose/ need for further pre-hospital naloxone within 12 hours of inclusion

    Measured: 12 hours

  10. reasons not to give rescue naloxone to non-responders

    Measured: The time participants are in the care of ambulance personnel, estimated 40 minutes

  11. follow-up after care

    Measured: The time participants are in the care of ambulance personnel, estimated 40 minutes

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 May 2018
  2. Study start15 May 2018
  3. Primary completion6 Oct 2020
  4. Study completion6 Oct 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Double blinded, double dummy, randomized controlled trial
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
286 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03518021
Sponsor's protocol ID
2016-004072-22
Other IDs
2016/2000, 2016-004072-22, 2016
Acronym
NINA-1
Status last verified
Oct 2020
First submitted
3 May 2018
Last updated
8 Oct 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: NTNU has complete ownership and publishing rights of all results, regardless of outcome. The full protocol, Statistical Analysis Plan, information letter for consent and other trial documents will be published open access in the NTNU Open repository. The Clinical Study report and Statistical Analysis Report will also be made openly available, but open versions may be censored to ensure that it will not be possible to identify individual study participants. The datasets analysed during the current study will be made available from NTNU upon reasonable request and a methodological sound proposal based on the consent given by participants.

Publications

  • Skulberg AK, Tylleskar I, Valberg M, Braarud AC, Dale J, Heyerdahl F, Skalhegg T, Barstein J, Mellesmo S, Dale O. Comparison of intranasal and intramuscular naloxone in opioid overdoses managed by ambulance staff: a double-dummy, randomised, controlled trial. Addiction. 2022 Jun;117(6):1658-1667. doi: 10.1111/add.15806. Epub 2022 Feb 8.

    PubMed 35137493

  • Skulberg AK, Tylleskar I, Braarud AC, Dale J, Heyerdahl F, Mellesmo S, Valberg M, Dale O. NTNU intranasal naloxone trial (NINA-1) study protocol for a double-blind, double-dummy, non-inferiority randomised controlled trial comparing intranasal 1.4 mg to intramuscular 0.8 mg naloxone for prehospital use. BMJ Open. 2020 Nov 12;10(11):e041556. doi: 10.1136/bmjopen-2020-041556.

    PubMed 33184084

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Naloxone, intranasal and Naloxone, intramuscular in people with Overdose and Drug Abuse, run by Norwegian University of Science and Technology at 2 sites in Norway.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: 40 minutes). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03518021, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2020.

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