Trial Review

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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12621000062820
Ethics application status
Approved
Date submitted
29/10/2020
Date registered
25/01/2021
Date last updated
11/01/2024
Date data sharing statement initially provided
25/01/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Effectiveness and safety of large bolus intramuscular naloxone for opioid poisoning in the Emergency Department
Scientific title
Effectiveness and safety of large bolus intramuscular naloxone for opioid poisoning in the Emergency Department: A randomised controlled trial
Secondary ID [1] 302656 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Opioid poisoning 319564 0
Condition category
Condition code
Emergency medicine 317507 317507 0 0
Other emergency care
Injuries and Accidents 318332 318332 0 0
Poisoning

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients in the treatment arm will receive a 100mcg bolus of intravenous naloxone and a single 1600mcg bolus of naloxone via the intramuscular route. Patients will then be managed along the standard opioid poisoning pathway where they are closely observed and receive 100mcg naloxone IV 5 minutely as required to reverse respiratory depression (defined as a respiratory rate >9 and oxygen saturations >92% on room air) until they are discharged from the Emergency Department.
Intervention code [1] 318943 0
Treatment: Drugs
Comparator / control treatment
Patients in the control arm will receive a 100mcg bolus of intravenous naloxone and a single bolus of normal saline via the intramuscular route. Patients will then be managed along the standard opioid poisoning pathway where they are closely observed and receive 100mcg naloxone IV 5 minutely as required to reverse respiratory depression (defined as a respiratory rate >9 and oxygen saturations >92% on room air) until they are discharged from the Emergency Department.
Control group
Placebo

Outcomes
Primary outcome [1] 325541 0
Proportion of patients with recurrence of opioid toxicity (defined as respiratory rate <10 and/or oxygen saturations <93%) documented in patient medical records.
Timepoint [1] 325541 0
4-hour period following the intramuscular administration of either 1.6mg naloxone or saline
Secondary outcome [1] 388351 0
Proportion of patients with reversal of opioid toxicity (defined as respiratory rate greater than or equal to 10 and oxygen saturations greater than or equal to 93%) documented in patient medical records.
Timepoint [1] 388351 0
10 minutes following naloxone administration
Secondary outcome [2] 388352 0
Total number of IV naloxone administrations documented in patient medical records.
Timepoint [2] 388352 0
During presentation
Secondary outcome [3] 403959 0
Rate of naloxone infusion administration documented in patient medical records
Timepoint [3] 403959 0
During patient presentation
Secondary outcome [4] 403960 0
Rate of any clinically significant features of withdrawal (tachycardia, hypertension, vomiting, acute behavioural disturbance, myocardial infarction, arrhythmia, pulmonary oedema, seizure, Subjective Opioid Withdrawal score) documented in patient medical records.
Timepoint [4] 403960 0
4-hour period following the intramuscular administration of either 1.6mg naloxone or saline

Eligibility
Key inclusion criteria
Adult patients > 17 years old presenting to the Princess Alexandra Hospital Emergency Department that require naloxone to reverse respiratory depression (defined as a respiratory rate < 10 or oxygen saturations < 93%) due to suspected opioid poisoning
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Patients in which intravenous access is unable to be obtained
• Patients who have iatrogenic poisoning following opioid administration for acute pain
• Patients who are intubated and ventilated for management of concurrent conditions such as aspiration pneumonitis or to facilitate management of co-ingestions agents.
• Patients in police or corrections custody

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 is concealed by allocation of sealed opaque envelopes.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Sequence generation will be randomised by using a randomisation table created by computer software.
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
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Sample Size and Feasibility
Based on our recent retrospective series which reported a difference in the rate of naloxone infusions of 39% in the titrated IV naloxone group compared to 10% in the large bolus IM naloxone group following suspected poisoning and using an alpha value of 0.05 and a 1-beta value of 95% with a 5% adjustment for cross-over a sample size of 63 is required in each arm (126 total).
In the first 6 months of 2020 there were 69 patients with opioid poisoning who presented to the Princess Alexandra Hospital and received naloxone. Based on our retrospective series 60% of these patients receive naloxone in the emergency department with the other 40% receiving it in the field and needing no further naloxone. This would mean approximately 80 patients each year would be eligible for the study. It is likely the required sample size could be recruited in two years.

Statistical analysis
Data will be analysed with descriptive statistics with continuous variables reported as medians, interquartile ranges and ranges. Dichotomous variables will be reported as proportions with 95% confidence intervals. Differences in groups will be assessed by Chi squared or Fisher’s exact test. A P-value of <0.05 will be considered statistically significant. A pre-defined subgroup for analysis is those that received naloxone in the pre-hospital setting prior to arrival to the Emergency Department.. Analysis will be performed in GraphPad Prism 8.3 for Mac OS (GraphPad Software, La Jolla, CA, USA).

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/10/2021
Actual
14/10/2021
Date of last participant enrolment
Anticipated
Actual
18/10/2023
Date of last data collection
Anticipated
Actual
18/10/2023
Sample size
Target
126
Accrual to date
Final
136
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 17914 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 31777 0
4102 - Woolloongabba

Funding & Sponsors
Funding source category [1] 307092 0
Hospital
Name [1] 307092 0
Princess Alexandra Hosptial
Country [1] 307092 0
Australia
Funding source category [2] 314513 0
Government body
Name [2] 314513 0
Queensland Advancing Clinical Research Fellowship
Country [2] 314513 0
Australia
Primary sponsor type
Hospital
Name
Princess Alexandra Hospital Clinical Toxicology Unit
Address
Ipswich Rd
Woolloongabba QLD 4012
Country
Australia
Secondary sponsor category [1] 307663 0
None
Name [1] 307663 0
Address [1] 307663 0
Country [1] 307663 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307209 0
Metro South HREC
Ethics committee address [1] 307209 0
Ethics committee country [1] 307209 0
Australia
Date submitted for ethics approval [1] 307209 0
12/11/2020
Approval date [1] 307209 0
14/12/2020
Ethics approval number [1] 307209 0
HREC/2020/QMS/70142

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

Contacts
Principal investigator
Name 106414 0
Dr Katherine Isoardi
Address 106414 0
Clinical Toxicology Unit Princess Alexandra Hospital Ipswich Rd Woolloongabba Q 4102
Country 106414 0
Australia
Phone 106414 0
+61 731763791
Fax 106414 0
Email 106414 0
[email protected]
Contact person for public queries
Name 106415 0
Katherine Isoardi
Address 106415 0
Clinical Toxicology Unit Princess Alexandra Hospital Ipswich Rd Woolloongabba Q 4102
Country 106415 0
Australia
Phone 106415 0
+61 731763791
Fax 106415 0
Email 106415 0
[email protected]
Contact person for scientific queries
Name 106416 0
Katherine Isoardi
Address 106416 0
Clinical Toxicology Unit Princess Alexandra Hospital Ipswich Rd Woolloongabba Q 4102
Country 106416 0
Australia
Phone 106416 0
+61 731763791
Fax 106416 0
Email 106416 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
Yes
Will there be any conditions when requesting access to individual participant data?
Persons/groups eligible to request access:
• Researchers who provide a methodologically sound proposal

Conditions for requesting access:
• -

What individual participant data might be shared?
• All of the individual participant data collected during the trial, after de-identification

What types of analyses could be done with individual participant data?
• Analysis to achieve the aims in the approved proposal

When can requests for individual participant data be made (start and end dates)?
From:
Immediately following publication, no end date

To:
-

Where can requests to access individual participant data be made, or data be obtained directly?
• Can access subject to approval by Principal Investigator Dr Katherine Isoardi ([email protected])

Are there extra considerations when requesting access to individual participant data?
No


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
9573Study protocol  [email protected] Study-related document.docx
16939Study protocol    Study protocol amended to version 3 Study-related document.docx



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.