Trial Review

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Trial registered on ANZCTR


Registration number
Help: Registration number
ACTRN12626000982314p
Ethics application status
Help: Ethics application status
Submitted, not yet approved
Date submitted
Help: Date submitted
20/07/2026
Date registered
Help: Date registered
11/08/2026
Date last updated
Help: Date last updated
11/08/2026
Date data sharing statement initially provided
Help: Data sharing statement date
11/08/2026
Type of registration
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Prospectively registered

Titles & IDs
Public title
Intranasal naloxone for the reversal of opioid overdose
Scientific title
An open-label non-inferiority trial of intranasal naloxone for the reversal of opioid overdose in Melbourne’s Medically Supervised Injecting Room
Additional trial identifiers [1] 317959 0
None
Universal Trial Number (UTN)
Trial acronym
INNAL
Related trial records

Health condition
Health condition(s) studied:
Opioid overdose 342924 0
Condition category
Condition code
Mental Health 339042 339042 0 0
Addiction
Public Health 339043 339043 0 0
Health service research

Intervention/exposure
Study type
Interventional
Description of the intervention or exposure
Participants will be randomly assigned to receive either an intranasal spray (intervention arm) or an intramuscular injection (control arm). The trial will be conducted over a 24-month period.

Participants in the intervention arm will receive one dose of 2 mg of intranasal naloxone hydrochloride once. Commercially available intranasal spray- Nyxoid, in a pre-filled intranasal delivery device containing 2 mg of Naloxone hydrochloride in 0.1 ml of fluid will be used.

The intranasal delivery device will be inserted into one nostril and the plunger depressed, delivering the contents as a fine atomised spray.

Intervention code [1] 334826 0
Treatment: Drugs
Description of the comparator or control
Participants in the control arm will receive 800 mcg of intramuscular naloxone hydrochloride. Commercially available pre-filled intramuscular injection- Prenoxad containing 1 mg of Naloxone hydrochloride per 1 ml will be used.

The injection will be delivered to a suitable large muscle, such as the deltoid.
Control group
Active

Outcomes
Primary outcome [1] 346285 0
Participant response to naloxone, defined as response without the requirement for a rescue dose of naloxone 10 minutes after administration of naloxone
Timepoint [1] 346285 0
10 mins post naloxone administration
Secondary outcome [1] 465313 0
Time from study drug administration to adequate respiration of greater than or equal to 8 breaths per minute
Timepoint [1] 465313 0
Continuously assessed from study drug administration until adequate respiration of greater than or equal to 8 breaths per minute is achieved.
Secondary outcome [2] 465314 0
Time from study drug administration to return to alertness defined as achieving “Alert” on the AVPU (Alert, Verbal, Pain, Unresponsive) scale.
Timepoint [2] 465314 0
Continuously assessed from study drug administration until the participant achieves an AVPU score of Alert.
Secondary outcome [3] 465315 0
Time from study drug administration to adequate oxygen saturation (SpO2) of greater than or equal to 95%
Timepoint [3] 465315 0
Continuously assessed from study drug administration until the participant achieves an oxygen saturation (SpO2) of greater than or equal to 95%
Secondary outcome [4] 465316 0
Drug residues detected in drug paraphernalia (typically needles/syringes but may also include mixing spoons) used at the overdose event. Drugs screened for include opioids (e.g. morphine), stimulants (e.g. methamphetamine), benzodiazepines (e.g. alprazolam), and other drugs identified through ongoing surveillance.
Timepoint [4] 465316 0
Once weekly throughout the 24-month study period.
Secondary outcome [5] 465556 0
Opioid withdrawal
Timepoint [5] 465556 0
15 minutes, 30 minutes and 24 hours (recorded within 1-7 days) post administration of naloxone
Secondary outcome [6] 465557 0
General wellbeing
Timepoint [6] 465557 0
24 hours (recorded within 1-7 days) post administration of naloxone
Secondary outcome [7] 465558 0
Post-rescuscitaion use of alcohol or other drugs (composite outcome)
Timepoint [7] 465558 0
24 hours (recorded within 1-7 days) post administration of naloxone

Eligibility
Key inclusion criteria
Participants will be clients of the Medically Supervised Injecting Room (MSIR) who experience suspected overdose according to MSIR protocols and who have not chosen to opt out of the study.
Consistent with current MSIR protocols, only those who do not respond to five minutes of initial breathing support with 100% oxygen or bag-valve-mask (i.e. respiratory rate less than 8 breaths per minute, Glasgow Coma Scale score less than 13, and oxygen saturation less than or equal to 95%) will be eligible for inclusion.
To use the MSIR potential participants must:
• Indicate that they wish to inject drugs in the facility.
• Be aged 18 years or over.
• Not have any accompanying children.
• Not be pregnant.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Healthy volunteers
No
Key exclusion criteria
The study will follow MSIR exclusion criteria. They are:
• Pregnant women - If it is suspected by MSIR staff that a client may be pregnant, they are referred to a local alcohol or other drug program where they undergo a pregnancy test. The results are then returned to MSIR.
• Under eighteen years of age - If it is suspected a potential client may be under eighteen years old, formal identification (ID) is requested of the potential client by MSIR staff. If the person is over eighteen, a copy of the ID is kept on file. If the person is under eighteen, they are referred to a local drug and alcohol service.
• Anyone who presents as already intoxicated.
• Anyone accompanied by a child.
• Anyone who has not previously injected drugs.
No additional study-specific exclusion criteria will be applied.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation concealment at the point of enrolment will be maintained using sequentially numbered, sealed randomisation envelopes prepared by a trial coordinator not involved in enrolment. Each envelope will represent one allocation and contain a description of the medication assigned for that allocation. Envelopes will be thick and truly opaque and sealed with tamper-evident tape. Envelopes will be labelled externally only with the sequence number. Envelopes will be opened in strict numerical order only after eligibility and consent are confirmed. All allocations and openings will be logged, and any deviations (e.g. damaged seal) will be documented and reported.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer-generated sequence with permuted blocks of varying sizes (e.g., 4 or 6)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis
Primary Outcome: Response to naloxone administration (defined as adequate response within 10 minutes and no need for a rescue naloxone dose).
Our choice of response time (10 minutes) is informed by our previous trials and our choice of control dose (naloxone IM 800 mcg) is informed by pharmacokinetic data that suggest 2 mg/0.1ml intranasal naloxone should not produce an inferior response 10 minutes after administration. Assuming a patient response to 800 mcg naloxone administered intramuscularly of 92% (population response rate estimated from random effect meta-analysis of our existing trial study data) and assuming a margin of 10%, we estimate 164 overdose events per arm are required to test non-inferiority of 2 mg/0.1ml naloxone administered intranasally (one-sided, 2.5% significance and 90% power). The sample size accounts for 2% attrition (as observed in our previous trial) and for an approximate 4% inflation in variance estimation (design effect [deff] equal to 1.04) given that single participants can be enrolled multiple times during the study period. This design effect derives from our calculations of the within-participant homogeneity observed in our previous trial in which 70/197 treated overdoses involved repeat presentations of individual clients. Using a closed testing procedure and assuming a 92% response to 800 mcg naloxone administered intramuscularly, this sample size will also permit exploration of superiority (where non-inferiority is demonstrated) of 2 mg/0.1ml naloxone administered intranasally with a minimum detectable difference of 7.3% (one-sided, 2.5% significance and 90% power). Previous pharmacokinetic data suggest superiority is a possibility.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
23/11/2026
Actual
Date of last participant enrolment
Anticipated
20/11/2028
Actual
Date of last data collection
Anticipated
30/11/2028
Actual
Sample size
Target
328
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment postcode(s) [1] 46242 0
3121 - Richmond North

Funding & Sponsors
Funding source category [1] 322507 0
Government body
Name [1] 322507 0
National Health and Medical Research Council (NHMRC)
Country [1] 322507 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Burnet Institute
Address
Country
Australia
Secondary sponsor category [1] 325428 0
None
Name [1] 325428 0
Address [1] 325428 0
Country [1] 325428 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 320994 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 320994 0
Ethics committee country [1] 320994 0
Australia
Date submitted for ethics approval [1] 320994 0
17/11/2025
Approval date [1] 320994 0
Ethics approval number [1] 320994 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 152298 0
Prof Paul Dietze
Address 152298 0
Burnet Institute, 85 Commercial Road, Melbourne, Victoria, Australia 3004
Country 152298 0
Australia
Phone 152298 0
+614 0953 0027
Fax 152298 0
Email 152298 0
[email protected]
Contact person for public queries
Name 152299 0
Paul Dietze
Address 152299 0
Burnet Institute, 85 Commercial Road, Melbourne, Victoria, Australia 3004
Country 152299 0
Australia
Phone 152299 0
+614 0953 0027
Fax 152299 0
Email 152299 0
[email protected]
Contact person for scientific queries
Name 152300 0
Paul Dietze
Address 152300 0
Burnet Institute, 85 Commercial Road, Melbourne, Victoria, Australia 3004
Country 152300 0
Australia
Phone 152300 0
+614 0953 0027
Fax 152300 0
Email 152300 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No


What supporting documents are/will be available?

TypeCitationLinkEmailOther DetailsAttachment
Ethical approval  [email protected]
Study protocol  [email protected]


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.