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Trial registered on ANZCTR


Registration number
ACTRN12611000852954
Ethics application status
Approved
Date submitted
8/08/2011
Date registered
10/08/2011
Date last updated
4/06/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Randomised, double-blinded clinical trial comparing intranasal and intramuscular naloxone for suspected opioid overdose
Scientific title
Randomised, double-blinded clinical trial comparing intranasal and intramuscular naloxone for reversal of suspected opioid overdose in clients of the Sydney Medically Supervised Injecting Centre
Secondary ID [1] 262801 0
Nil
Universal Trial Number (UTN)
U1111-1123-3396
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Suspected acute opioid overdose 270508 0
Condition category
Condition code
Public Health 270670 270670 0 0
Other public health

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
800mcg/mL active naloxone intranasally and intramuscular placebo, or 800mcg/mL active naloxone intramuscularly and intranasal placebo. This will be a 'once off' intervention. If a second dose is required, this will be by the standard procedure of 800mcg/2mL intramuscularly.

Contents of the vial for IN administration will be drawn into one syringe. Staff will attach the syringe to a MAD, and administer 0.5mL (400mcg) into each nostril, depressing the syringe rapidly to achieve adequate atomisation. In this way, each study participants will receive 0.5mL of fluid in each nostril. Supportive care/oxygenation will be administered simultaneously, in accordance with existing MSIC clinical protocols
Administration of the IM injection will be by standard practice of drawing the full 1ml into a single 5ml syringe and administering to the deltoid muscle via a 21g needle.
Intervention code [1] 269146 0
Treatment: Drugs
Comparator / control treatment
1 mL saline for both intramuscular and intranasal placebo
Control group
Placebo

Outcomes
Primary outcome [1] 269389 0
No requirement of second ("rescue") dose of naloxone. A second dose of naloxone may be required where the participant has not satisfactorily recovered 15 minutes after initial presentation of overdose, ie: if the participant's Glasgow Coma Score is less than 13 and/or their respiratory rate is less than 10/minute.
Timepoint [1] 269389 0
15 minutes after first presentation of overdose
Secondary outcome [1] 287529 0
Glasgow Coma Score (GCS) greater than or equal to 13 as observed by trained clinician
Timepoint [1] 287529 0
From first administration of naloxone until 10 minutes post administration
Secondary outcome [2] 287574 0
Respiration rate greater than or equal to 10 per minute as observed by trained clinician
Timepoint [2] 287574 0
From first administration of naloxone until 10 minutes post administration

Eligibility
Key inclusion criteria
All clients with symptoms/signs of an opioid overdose requiring Naloxone administration will be eligible for entry. This is based on existing and approved MSIC protocols and clinical criteria for overdose (reduced level of consciousness as measured by the Glasgow Coma Score, pinpoint pupils, respiratory depression and/or reduced oxygen saturations as measured by pulse oximetry).
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Less than 18 years of age
Pregnant or suspected of being pregnant

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)
The participants will be enrolled into the study after the informed consent process has been completed and the participant has met all inclusion criteria and none of the exclusion criteria. The allocation schedule will be held off-site by the pharmacy packaging company who are also responsible for the randomisation of the study packs. All clients are potentially participants. They are allocated to either the active intranansal or active intramuscular groups by virture of the randomisation procedure undertaken by the pharmaceutical packaging company who are supplying the study packs. Participants will be consecutively enrolled during all operating hours of the service. All clients of the MSIC will be informed of the study at registration. The participant will be informed of their enrollment once they have fully regained consciousness. If they decline to participate, the data will be eliminated from the database.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
MSIC staff will manage drug overdoses using existing clinical protocols. These state that a client will receive airway management and oxygenation either via a Hudson mask or artificial ventilation (bagging) for five minutes before being assessed as to the need for naloxone. Where a client’s response after five minutes is inadequate, naloxone will be administered by a registered nurse in accordance with existing standing orders from the Medical Director.
Study participants will receive a random allocation of naloxone in one of 2 forms:
a. Active intranasal naloxone and intramuscular placebo, or
b. Intranasal placebo and active intramuscular naloxone
Study packs will be pre-prepared and contain two clearly labelled vials – 1) Intranasal - naloxone 800mcg/1mL or placebo (1mL) for IN administration and 2) Intramuscular - 800mcg/1ml or placebo for IM administration. The vials will be labelled as intranasal and intramuscular, therefore the person administering the drugs will be blinded to the treatment arms.
Contents of the vial for IN administration will be drawn into one syringe. Staff will attach the syringe to a MAD, and administer 0.5mL (400mcg) into each nostril, depressing the syringe rapidly to achieve adequate atomisation. In this way, each study participants will receive 0.5mL of fluid in each nostril. Supportive care/oxygenation will be administered simultaneously, in accordance with existing MSIC clinical protocols
Administration of the IM injection will be by standard practice of drawing the full 1ml into a single 5ml syringe and administering to the deltoid muscle via a 21g needle.
The study packs will be randomised using computer sequence generation techniques by the pharmacy packaging company who are supplying the study packs.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 269623 0
Government body
Name [1] 269623 0
NSW Health
Address [1] 269623 0
73 Miller Street, North Sydney, NSW 2060
Country [1] 269623 0
Australia
Primary sponsor type
Other
Name
Sydney Medically Supervised Injecting Centre
Address
66 Darlinghurst Road, Kings Cross, NSW, 2011
Country
Australia
Secondary sponsor category [1] 266655 0
None
Name [1] 266655 0
Address [1] 266655 0
Country [1] 266655 0
Other collaborator category [1] 252184 0
University
Name [1] 252184 0
Victoria University
Address [1] 252184 0
Cnr Nicholson and Buckley Street, Footscray, Victoria, 3011
Country [1] 252184 0
Australia
Other collaborator category [2] 252186 0
Other
Name [2] 252186 0
Burnet Institute
Address [2] 252186 0
85 Commercial Road, Melbourne, Victoria, 3004
Country [2] 252186 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 269572 0
South Eastern Sydney Local Health District HREC Northern Sector
Ethics committee address [1] 269572 0
Room G71, Edmund Blackett Building, Prince of Wales Hospital, Randwick, NSW, 2031
Ethics committee country [1] 269572 0
Australia
Date submitted for ethics approval [1] 269572 0
Approval date [1] 269572 0
18/07/2011
Ethics approval number [1] 269572 0
1/10/0146

Summary
Brief summary
The aim of this study is to determine whether naloxone, an opioid reversal agent, is as effective for the treatment of acute opioid overdose when administered via the intranasal (IN) route compared with the intramuscular route. The term 'opioid' refers to a class of drugs that includes heroin, and the prescription medications oxycontin and morphine. Injection of naloxone into a muscle is currently the standard method of emergency treatment for an opioid overdose on site at the Sydney Medically Supervised Injecting Centre. However, Naloxone can be administered as an intranasal (IN) spray using a 'mucosal atomisation device’. Evidence suggests that IN naloxone may be an effective and practical alternative. The significant benefits of IN administration include removing the risk of needlestick injury (and thus any blood borne virus transmission risk) to treating personnel. This is particularly relevant to ambulance officers and paramedics, as well as other emergency health care workers, such as in the hospital emergency department setting.

Additionally, given the ease of administration and reduced issues regarding disposal of used needles, the availability of IN naloxone may potentially be extended. This may include non health care workers who regularly deal with opioid overdose in community settings, and drug users’ peers, who are likely to be present in the event of an overdose. The Sydney Medically Supervised Injecting Centre (MSIC) provides the ideal setting for this study.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 32992 0
Dr Marianne Jauncey
Address 32992 0
Sydney Medically Supervised Injecting Clinic, PO Box 293, Kings Cross, NSW, 1340
Country 32992 0
Australia
Phone 32992 0
+612 9360 1191
Fax 32992 0
Email 32992 0
mjauncey@unitingcarenswact.org.au
Contact person for public queries
Name 16239 0
Prof Paul Dietze
Address 16239 0
PO Box 293, Kings Cross, NSW, 1340
Country 16239 0
Australia
Phone 16239 0
+61 3 9282 2111
Fax 16239 0
Email 16239 0
paul.dietze@burnet.edu.au
Contact person for scientific queries
Name 7167 0
Dr Marianne Jauncey
Address 7167 0
PO Box 293, Kings Cross, NSW, 1340
Country 7167 0
Australia
Phone 7167 0
+61 2 9360 1191
Fax 7167 0
+61 2 9360 0707
Email 7167 0
mjauncey@sydneymsic.com

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary