Bacterial Infections
Conditions
Brief summary
A trial to assess cumulative incidence of skin and soft tissue infections (SSTI) in infants (by three months of age) born to mothers receiving a single-dose of 2 grams of oral azithromycin during labour (or immediately prior to delivery in the case of caesarean section), compared to infants whose mothers received placebo.
Detailed description
PreYIAL is a Phase III, double-blind, randomised, placebo controlled two arm trial of a single 2g dose of azithromycin or placebo, administered to women who have been admitted for delivery of their baby (either following onset of labour or for caesarean section). The trial includes an estimated 2110 mothers/infant pairs (1055 per arm), with 12 months of follow-up for the mother/infant pair. A swab-study within the main study involves 940 of the mother/infant pairs enrolled and involves follow-up for bacterial carriage outcomes, for 12 months.These swab-study participants will also be included in assessments of the infant and maternal microbiome.
Interventions
DRUGMatching Placebo
Matching Placebo
DRUGAzithromycin 500 mg Oral Tablet x 4
A single prophylactic dose of antibiotic given during labour
Sponsors
Ministry of Health, Fiji
Murdoch Childrens Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Matched drug and placebo
Intervention model description
Blinded, randomized, placebo-controlled trial
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Pregnant women at least 18 years old intending to deliver at Colonial War Memorial Hospital (CWMH) 2. Women who have been admitted to CWMH for delivery at the time of eligibility assessment 3. Women who expect to be available, with their infant, for the duration of the study, and who agree to adhere to all protocol requirements 4. Women who will have a main place of residence within the Greater Suva area for the follow-up period and within a practical distance of the study site to allow compliance with protocol-required visits and follow-up, including attending follow-up at specified clinics 5. Women who have provided written informed consent prior to study-related procedures being performed
Exclusion criteria
1. Women who have a known macrolide allergy 2. Women who have taken antibiotics in the week prior to randomisation 3. A women who is unable or unwilling to provide informed consent for her participation in the trial or the participation of her infant 4. Women who decide prior to randomisation that they are no longer willing to participate or to have their infant participate 5. Women who have ever received, or who are anticipated to receive during the study period, any investigational agent other than the study drug 6. Women who are CWMH, Murdoch Children's Research Institute (MCRI) or study site employees who work directly with study staff, or who are working on the study 7. Women taking warfarin due to the potential for drug interactions with azithromycin 8. Women with any cardiac abnormality 9. Women taking other medications known to prolong the QT interval such as antiarrhythmics; antipsychotic agents; antidepressants; and fluoroquinolones; 10. Women with known electrolyte disturbances: including in cases of hypokalaemia and hypomagnesaemia 11. Women who will undergo general anaesthetic for delivery 12. Women carrying a foetus with intrauterine death confirmed before randomisation 13. Women carrying a foetus with a prognosis unlikely to survive 14. Women with known HIV infection and/or taking nelfinavir 15. Women who have participated in the study during a previous pregnancy 16. Women who have been admitted for management of premature labour who have unruptured membranes (This is a temporary exclusion such that the participant may be assessed for eligibility again in the same or a subsequent admission to CWMH). 17. Women with renal impairment 18. Women with hepatic impairment 19. Women with myasthenia gravis 20. Women who are taking any ergot medications
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative incidence of skin and soft tissue infection by 3 months of age in infants | 3 months | Born to mothers receiving a single dose of 2g Azithromycin during labour. Assessed by history and physical examination at 7 days, 6 weeks and 3 months. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative incidence of maternal infection by 6 weeks and 12 months post-delivery | Delivery to 12 months | To compare intervention and placebo groups with regard to the cumulative incidence of maternal infection (mastitis, sepsis, post-operative wound infections, SSTI, fever, meningitis, pneumonia, abdominal or pelvic abscess, endometritis, urinary tract infection, pyelonephritis) by six weeks post-delivery, and similarly up to 12 months post-delivery |
| Cumulative incidence of antibiotic usage by 12 months in infants | Birth to 12 months | To compare intervention and placebo groups with regard to the cumulative incidence of the number of courses of antibiotics prescribed to the infant up to 12 months of age; |
| Cumulative incidence of maternal antibiotic usage by 12 months post-delivery | Delivery to 12 months | To compare intervention and placebo groups with regard to the cumulative incidence of the number of courses of antibiotics prescribed to the mother up to 12 months post-delivery |
| Number of infant participants with adverse events as assessed by adapted version of CTCAE v5.0 and DAID v2.1 | Birth to 12 months | To compare the number of adverse events including solicited non serious adverse events and all serious adverse events as per study specific definitions throughout the duration of the study. |
| Number of maternal participants with adverse events as assessed by adapted version of CTCAE v5.0 and DAID v2.1 | Delivery to 12 months | To compare the number of adverse events including solicited non serious adverse events and all serious adverse events as per study specific definitions throughout the duration of the study. |
| Number of infant and maternal participants with Staphylococcus aureus and/or Group A streptococcus as assessed by real-time quantitative PCR (qPCR) from impetigo swabs | Delivery/birth to 12 months | The proportion of participants that have Staphylococcus aureus and/or Group A streptoccoccus detected by qPCR from impetigo swabs at key time points throughout the duration of the study, between the two groups |
| Cumulative incidence of skin and soft tissue infection, and other infections by 12 months of age in infants | Birth to 12 Months | To compare intervention and placebo groups with regard to the cumulative incidence of infant infection (meningitis, sepsis, pneumonia, SSTI, fever, diarrhoea, urinary tract infection) up to 12 months of age; |
| Swab study outcome - Prevalence of bacterial carriage as assessed by real-time quantitative PCR (qPCR) | Delivery/birth to 12 months | Bacterial carriage, the proportion of participants that have at least one of the following bacterial species including GBS, SA, SPN, GAS or E. coli, assessed by qPCR at key time points throughout the duration of the study, between the two groups |
| Swab study outcome - Density of bacterial carriage as assessed by real-time quantitative PCR (qPCR) | Delivery/birth to 12 months | Density of bacterial carriage, reported as log 10 genome equivalents/ml, of the participants that have at least one of the following bacterial species including GBS, SA, SPN, GAS or E. coli, assessed by qPCR at key time points throughout the duration of the study, between the two groups |
| Swab study outcome - Risk of maternal carriage identified through qPCR of common organisms relevant to Sexually Transmitted Infections (STI) | Delivery/birth to 6 months | Maternal carriage of common organisms relevant to Sexually Transmitted Infections (STI) (including Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Mycoplasma genitalium, HSV-1 and HSV-2) as detected by qPCR at key time points throughout the duration of the study, between the two groups. |
| Swab study outcome - Risk of antibiotic nonsusceptibility in culture isolates | Delivery/birth to 12 months | Antibiotic non susceptibility, based on the proportion of samples from mothers and infants that are non susceptible to antibiotics cultured in the two arms, at key time points throughout the duration of the study |
| Swab study outcome - The prevalence of infants with diagnoses that have been associated with microbiome dysbiosis | Delivery/birth to 6 months | To compare the infant and maternal microbiome of specified body sites at key time points in the intervention and placebo groups |
| Number of infant and maternal participants with Staphylococcus aureus and/or Group A streptococcus with azithromycin nonsusceptibility cultured from impetigo swabs. | Delivery/birth to 12 months | The proportion of participants that have Staphylococcus aureus and/or Group A streptococcus that is non susceptible to azithromycin cultured from impetigo swabs at key time points throughout the duration of the study, between the two groups |
Countries
Fiji
Outcome results
None listed