None listed
Conditions
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.
Interventions
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,
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.
Sponsors
The University of Melbourne
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Prevention
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Healthy volunteers
No
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.
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).
Outcome results
None listed