ANZCTR - Registration

The ANZCTR website is back online for trial registration and updates. We apologise for any inconvenience caused while the site was inactive.

Reset your password and enable multi-factor authentication (MFA)

For ANZCTR account holders: to help ensure the cyber safety of your account, you’ll need to reset your password and set-up multi-factor authentication (MFA) as per the instructions below.

Go to the Login page, click ‘reset password’ and follow the instructions.
Check your email for the link to set a new password.
Create a new password that meets requirements. New passwords must include at least one lowercase letter, one uppercase letter, one number and one special character (e.g. !#$%&@).
Return to the Login page and enter your new password. A verification code will be sent to your email.
Check your email for the code and enter it on the Login page. If the code is entered incorrectly, you can re-enter the correct one or request a new one.

Learn more about MFA and its importance on the Australian Signals Directorate website.

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

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]

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

Condition category

Condition code

Infection

Studies of infection and infectious agents

Public Health

Other public health

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]

Prevention

Comparator / control treatment

No treatment Arm

Control group

Active

Outcomes

Primary outcome [1]

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]

Baseline and Day 14 post-baseline

Secondary outcome [1]

Frequency of pharyngeal carriage of a GAS strain homologous with the index case

Timepoint [1]

Baseline, Day14 post-baseline, Day30 post-baseline

Secondary outcome [2]

Frequency of iGAS and non-invasive GAS disease. This will be assessed as a composite outcome

Timepoint [2]

Baseline, Day 14 post-baseline and Day 30 post-baseline

Secondary outcome [3]

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 [3]

Post-baseline Day 14 and Day 30.

Secondary outcome [4]

Compliance of prescribed antibiotics

Timepoint [4]

Day 14 post-baseline

Secondary outcome [5]

Acceptability of prescribed antibiotics

Timepoint [5]

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?

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]

Government body

Name [1]

NHMRC

Address [1]

Country [1]

Australia

Primary sponsor type

University

Name

The University of Melbourne

Address

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

The Royal Melbourne Hospital Human Research Ethics Committee

Ethics committee address [1]

https://www.thermh.org.au/research/researchers/ethics

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

06/11/2024

Approval date [1]

28/01/2025

Ethics approval number [1]

Summary

Brief summary

Invasive group A Strep (iGAS) is a severe infection that can lead to death or lifelong disability in people of all ages.

When someone is diagnosed with iGAS, their household members have a much higher risk (2000x) of developing the same infection within the next month, a condition known as secondary iGAS, similar to the risk associated with meningococcal disease.

While close contacts of meningococcal disease cases are routinely prescribed preventive antibiotics, only mother-baby pairs are routinely given preventive antibiotics for secondary iGAS, leaving a lack of guidance for other household members. The ISAAC study aims to understand if other household contacts of iGAS cases should also be prescribed preventive antibiotics.

The study also aims to find out if taking a single dose of oral azithromycin is better than not taking any antibiotics at all, and if taking this shorter, single-dose oral antibiotic course could be as effective as the currently recommended longer or injectable antibiotic courses. Because these options are either  long or  painful, a single once-off oral medication (that you swallow) might be more preferable to household members. 
The trial aims to inform the public health management of invasive Strep A (iGAS) infections. Currently, household contacts are at a 2000 fold higher risk of also becoming unwell with iGAS in the 30 days after an initial case of iGAS. We think antibiotics are important to reduce this risk, but need to demonstrate both effectiveness of antibiotics and which antibiotic is the best to use. These are the main two questions of the trial.

By generating evidence on the need for preventive antibiotics among household contacts of iGAS cases and exploring alternative antibiotic options, the ISAAC study hopes to better inform public health authorities and doctors across Australia on how to best manage iGAS cases.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

A/Prof Katherine Gibney

Address

Department of Infectious Diseases, University of Melbourne at the Peter Doherty Institute of Infection and Immunity 792 Elizabeth Street, Melbourne Victoria 3000

Country

Australia

Phone

+610435952174

Fax

[email protected]

Contact person for public queries

Name

Katherine Gibney

Address

Department of Infectious Diseases, University of Melbourne at the Peter Doherty Institute of Infection and Immunity 792 Elizabeth Street, Melbourne Victoria 3000

Country

Australia

Phone

+610435952174

Fax

[email protected]

Contact person for scientific queries

Name

Katherine Gibney

Address

Department of Infectious Diseases, University of Melbourne at the Peter Doherty Institute of Infection and Immunity 792 Elizabeth Street, Melbourne Victoria 3000

Country

Australia

Phone

+610435952174

Fax

[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?

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.

Trial Review

Documents added manually

Documents added automatically