Preventing Young Infant Infections Using Azithromycin in Labour (PreYIAL) Trial

Sponsor
Murdoch Childrens Research Institute (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT03925480
Collaborator
Ministry of Health, Fiji (Other)
2,110
1
2
46
45.9

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Azithromycin 500 mg Oral Tablet x 4
  • Drug: Matching Placebo
Phase 3

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
2110 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Blinded, randomized, placebo-controlled trialBlinded, randomized, placebo-controlled trial
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Matched drug and placebo
Primary Purpose:
Prevention
Official Title:
Preventing Young Infant Infections Using Azithromycin in Labour (PreYIAL): a Blinded, Randomised, Placebo-controlled Trial
Actual Study Start Date :
Jul 1, 2019
Actual Primary Completion Date :
Mar 30, 2022
Anticipated Study Completion Date :
Apr 30, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Azithromycin

A single 2g dose of Azithromycin

Drug: Azithromycin 500 mg Oral Tablet x 4
A single prophylactic dose of antibiotic given during labour

Placebo Comparator: Placebo

Matching Placebo

Drug: Matching Placebo
Matching Placebo

Outcome Measures

Primary Outcome Measures

  1. 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 Outcome Measures

  1. 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;

  2. 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

  3. 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;

  4. 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

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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.

  12. 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

  13. Swab study outcome - Effects of the intervention on the infant and maternal microbiome of specified body sites [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

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
Female
Accepts 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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Colonial War Memorial Hospital and Mother and Child Health Clinics Suva Central Fiji

Sponsors and Collaborators

  • Murdoch Childrens Research Institute
  • Ministry of Health, Fiji

Investigators

  • Principal Investigator: Fiona M Russell, BMBS PhD, Murdoch Childrens Research Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Fiona Russell, Professor, Murdoch Childrens Research Institute
ClinicalTrials.gov Identifier:
NCT03925480
Other Study ID Numbers:
  • HREC 38057
First Posted:
Apr 24, 2019
Last Update Posted:
Aug 12, 2022
Last Verified:
Aug 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Product Manufactured in and Exported from the U.S.:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Aug 12, 2022