Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625000375459
Ethics application status
Approved
Date submitted
4/04/2025
Date registered
28/04/2025
Date last updated
28/04/2025
Date data sharing statement initially provided
28/04/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
ISAAC: Invasive Strep A: defining the role of Antibiotic prophylaxis in Contact management
Scientific title
A Randomized, Open Label, Multisite Trial of Antibiotic Prophylaxis to Reduce Group A Streptococcus (GAS) Pharyngeal Carriage Among Household Contacts of Invasive Group A Streptococcal Disease (iGAS) Cases.
Secondary ID [1] 313290 0
NIL
Universal Trial Number (UTN)
NIL
Trial acronym
ISAAC
Linked study record
NIL

Health condition
Health condition(s) or problem(s) studied:
Invasive Group A Streptococcal Disease 336939 0
Condition category
Condition code
Public Health 333422 333422 0 0
Other public health
Infection 333410 333410 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will be randomly allocated to 1 of the 3 following treatment arms:

-Azithromycin, Oral Tablet, Single dose, 1g (child 20mg/kg, up to 1g). Liquid formulation will be used Only for paediatric participants who are unable to swallow tablets.
Intravenous (IV) azithromycin may be used is a neonate in special care nursery and who
has pre-existing IV access and who is unable to take an oral formulation
of azithromycin.

-Cefalexin, Oral tablet, Twice daily for 10 days, 1g (child 25 mg/kg, up to 1 g)

-Benzathine penicillin, Intramuscular, Single dose,
Adult or child equal or greater than 20 kg: 1.2 million units (2.3 mL)
Child between 10 kg to less than 20 kg: 0.6 million units (1.2 mL)
Child less than 10 kg: 0.45 million units (0.9 mL)

The oral formulation of the antibiotics, oral tablet and liquid suspension, will be self-administered by the participant. The intramuscular injection will be administered by a local physician.
The Sponsor will perform regular onsite and remote monitoring of the staff training and delegation logs to verify compliance with study protocol and Good Clinical Practice requirements. Participants will be asked to answer surveys to provide updates on adherence to antibiotic self –administration. Where the intramuscular injection will be administered locally, the study medication records will be checked against the participant enrolment list.
Intervention code [1] 330719 0
Prevention
Comparator / control treatment
No treatment Arm
Control group
Active

Outcomes
Primary outcome [1] 340985 0
Comparative effectiveness in clearance of pharyngeal GAS of: • Single dose oral azithromycin versus no antibiotic prophylaxis, • ß-lactam antibiotics versus no antibiotics, and • Single dose azithromycin versus ß-lactam antibiotics.
Timepoint [1] 340985 0
Baseline and Day 14 post-baseline
Secondary outcome [1] 445679 0
Frequency of iGAS and non-invasive GAS disease. This will be assessed as a composite outcome
Timepoint [1] 445679 0
Baseline, Day 14 post-baseline and Day 30 post-baseline
Secondary outcome [2] 445678 0
Frequency of pharyngeal carriage of a GAS strain homologous with the index case
Timepoint [2] 445678 0
Baseline, Day14 post-baseline, Day30 post-baseline
Secondary outcome [3] 446264 0
Acceptability of prescribed antibiotics
Timepoint [3] 446264 0
Day 14 post-baseline
Secondary outcome [4] 445681 0
Safety and tolerability (side effects) of prescribed antibiotics. Some common side efftects as reported in the product information are: nausea, vomiting, diarrhoea, abdominal pain and cramps. Some of the known rare side effects ( less than 0.1% ) include Torsades de pointes (very rare), ototoxicity, neurotoxicity.
Timepoint [4] 445681 0
Post-baseline Day 14 and Day 30.
Secondary outcome [5] 445682 0
Compliance of prescribed antibiotics
Timepoint [5] 445682 0
Day 14 post-baseline

Eligibility
Key inclusion criteria
1. Meets the trial definition of a household contact of an iGAS case.
2. Provided informed consent, or guardian / medical treatment decision maker
provided informed consent.
3. Able to undertake trial activities within protocol mandated time window.
4. Enrolled within 10 days of notification of the index iGAS case to public
health.
Minimum age
No limit
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Received any antibiotics in the past 7 days (at the time of screening).
2. Excluded from at least two of the trial arms.
3. Significant concomitant illnesses, condition or behaviour which, in the
investigator’s opinion, does not make the participant a good candidate for
the trial.
ARM SPECIFIC EXCLUSION CRITERIA:
ARM 1 [no antibiotics arm]
• People who have given birth in the past 28 days.
• Neonate less than or equal to 28 days of age.
• Antibiotic prophylaxis recommended in national or jurisdictional iGAS
contact management guidelines.
• Antibiotic prophylaxis recommended by treating clinician (i.e. the treating
clinician has indicated the participant should not be randomised to the ‘no
antibiotic’ arm).
ARM 2 [azithromycin arm]
• Allergy to azithromycin or other macrolide antibiotics (i.e., clarithromycin
or erythromycin).
ARM 3 [ß-lactam arm]
• Anaphylactic reaction to any penicillin-containing antibiotic, cephalosporin
antibiotic, or carbapenem antibiotic.
• Allergy to both penicillin and cefalexin (or cefalexin alone in settings where
IM benzathine penicillin is not preferred).

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed for this trial.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation is stratified by jurisdiction, household size (smaller or larger as per Key
Definitions) and eligibility
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
30/07/2025
Actual
Date of last participant enrolment
Anticipated
30/06/2028
Actual
Date of last data collection
Anticipated
1/08/2028
Actual
Sample size
Target
1809
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,NT,QLD,WA,VIC

Funding & Sponsors
Funding source category [1] 317740 0
Government body
Name [1] 317740 0
NHMRC
Country [1] 317740 0
Australia
Primary sponsor type
University
Name
The University of Melbourne
Address
Country
Australia
Secondary sponsor category [1] 321063 0
None
Name [1] 321063 0
Address [1] 321063 0
Country [1] 321063 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 316428 0
The Royal Melbourne Hospital Human Research Ethics Committee
Ethics committee address [1] 316428 0
Ethics committee country [1] 316428 0
Australia
Date submitted for ethics approval [1] 316428 0
06/11/2024
Approval date [1] 316428 0
28/01/2025
Ethics approval number [1] 316428 0

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

Contacts
Principal investigator
Name 137862 0
A/Prof Katherine Gibney
Address 137862 0
Department of Infectious Diseases, University of Melbourne at the Peter Doherty Institute of Infection and Immunity 792 Elizabeth Street, Melbourne Victoria 3000
Country 137862 0
Australia
Phone 137862 0
+610435952174
Fax 137862 0
Email 137862 0
[email protected]
Contact person for public queries
Name 137863 0
Katherine Gibney
Address 137863 0
Department of Infectious Diseases, University of Melbourne at the Peter Doherty Institute of Infection and Immunity 792 Elizabeth Street, Melbourne Victoria 3000
Country 137863 0
Australia
Phone 137863 0
+610435952174
Fax 137863 0
Email 137863 0
[email protected]
Contact person for scientific queries
Name 137864 0
Katherine Gibney
Address 137864 0
Department of Infectious Diseases, University of Melbourne at the Peter Doherty Institute of Infection and Immunity 792 Elizabeth Street, Melbourne Victoria 3000
Country 137864 0
Australia
Phone 137864 0
+610435952174
Fax 137864 0
Email 137864 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
Conditions for requesting access:
• Yes, conditions apply:
• Requires review on a case-by-case basis by the trial custodian, sponsor or data sharing committee
• Requires a scientifically sound proposal or protocol
• Requires approval by an ethics committee
• Requires a data sharing agreement between data requester and trial custodian or sponsor
What individual participant data might be shared?
• De-identified individual participant data:
• Published results
• Primary outcome(s)
What types of analyses could be done with individual participant data?
• Systematic reviews and meta-analyses
• Studies exploring new research questions
• Health economic analyses
• Studies testing whether findings can be repeated or confirmed
When can requests for individual participant data be made (start and end dates)?
From:
At the end of the study
To:
Not yet decided
Where can requests to access individual participant data be made, or data be obtained directly?
• Email of trial custodian, sponsor or committee: Principal Investigator: [email protected]

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


What supporting documents are/will be available?

No Supporting Document Provided


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.