Clinical trial NCT03925480: Preventing Young Infant Infections Using Azithromycin in Labour (PreYIAL) Trial
Official title: Preventing Young Infant Infections Using Azithromycin in Labour (PreYIAL): a Blinded, Randomised, Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Bacterial Infections
Lead sponsor: Murdoch Childrens Research Institute
Sponsor class: OTHER
Collaborators: name: Ministry of Health, Fiji
First posted: 2019-04-24
Enrollment: 2110
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Blinded, randomized, placebo-controlled trial
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Cumulative incidence of skin and soft tissue infection by 3 months of age in infants
timeFrame: 3 months
Secondary outcomes:
measure: Cumulative incidence of skin and soft tissue infection, and other infections by 12 months of age in infants
timeFrame: Birth to 12 Months
measure: Cumulative incidence of maternal infection by 6 weeks and 12 months post-delivery
timeFrame: Delivery to 12 months
measure: Cumulative incidence of antibiotic usage by 12 months in infants
timeFrame: Birth to 12 months
measure: Cumulative incidence of maternal antibiotic usage by 12 months post-delivery
timeFrame: Delivery to 12 months
measure: Number of infant participants with adverse events as assessed by adapted version of CTCAE v5.0 and DAID v2.1
timeFrame: Birth to 12 months
measure: Number of maternal participants with adverse events as assessed by adapted version of CTCAE v5.0 and DAID v2.1
timeFrame: Delivery to 12 months
measure: 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
timeFrame: Delivery/birth to 12 months
measure: Number of infant and maternal participants with Staphylococcus aureus and/or Group A streptococcus with azithromycin nonsusceptibility cultured from impetigo swabs.
timeFrame: Delivery/birth to 12 months
measure: Swab study outcome - Prevalence of bacterial carriage as assessed by real-time quantitative PCR (qPCR)
timeFrame: Delivery/birth to 12 months
measure: Swab study outcome - Density of bacterial carriage as assessed by real-time quantitative PCR (qPCR)
timeFrame: Delivery/birth to 12 months
measure: Swab study outcome - Risk of maternal carriage identified through qPCR of common organisms relevant to Sexually Transmitted Infections (STI)
timeFrame: Delivery/birth to 6 months
measure: Swab study outcome - Risk of antibiotic nonsusceptibility in culture isolates
timeFrame: Delivery/birth to 12 months
measure: Swab study outcome - The prevalence of infants with diagnoses that have been associated with microbiome dysbiosis
timeFrame: Delivery/birth to 6 months
Other outcomes:
Locations:
city: Suva
country: Fiji
facility: Colonial War Memorial Hospital and Mother and Child Health Clinics
state: Central
Study officials:
affiliation: Murdoch Childrens Research Institute
name: Fiona M Russell, BMBS PhD
role: PRINCIPAL_INVESTIGATOR
References: