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

Primary Purpose

Bacterial Infections

Status

Completed

Phase

Phase 3

Locations

Fiji

Study Type

Interventional

Intervention

Azithromycin 500 mg Oral Tablet x 4

Matching Placebo

About this trial

This is an interventional prevention trial for Bacterial Infections

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion criteria:

Pregnant women at least 18 years old intending to deliver at Colonial War Memorial Hospital (CWMH)
Women who have been admitted to CWMH for delivery at the time of eligibility assessment
Women who expect to be available, with their infant, for the duration of the study, and who agree to adhere to all protocol requirements
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
Women who have provided written informed consent prior to study-related procedures being performed

Exclusion criteria:

Women who have a known macrolide allergy
Women who have taken antibiotics in the week prior to randomisation
A women who is unable or unwilling to provide informed consent for her participation in the trial or the participation of her infant
Women who decide prior to randomisation that they are no longer willing to participate or to have their infant participate
Women who have ever received, or who are anticipated to receive during the study period, any investigational agent other than the study drug
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
Women taking warfarin due to the potential for drug interactions with azithromycin
Women with any cardiac abnormality
Women taking other medications known to prolong the QT interval such as antiarrhythmics; antipsychotic agents; antidepressants; and fluoroquinolones;
Women with known electrolyte disturbances: including in cases of hypokalaemia and hypomagnesaemia
Women who will undergo general anaesthetic for delivery
Women carrying a foetus with intrauterine death confirmed before randomisation
Women carrying a foetus with a prognosis unlikely to survive
Women with known HIV infection and/or taking nelfinavir
Women who have participated in the study during a previous pregnancy
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).
Women with renal impairment
Women with hepatic impairment
Women with myasthenia gravis
Women who are taking any ergot medications

Sites / Locations

Colonial War Memorial Hospital and Mother and Child Health Clinics

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Azithromycin

Placebo

Arm Description

A single 2g dose of Azithromycin

Matching Placebo

Outcomes

Primary Outcome Measures

Cumulative incidence of skin and soft tissue infection by 3 months of age in infants

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

Cumulative incidence of skin and soft tissue infection, and other infections by 12 months of age in infants

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;

Cumulative incidence of maternal infection by 6 weeks and 12 months post-delivery

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

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

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

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

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

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

Number of infant and maternal participants with Staphylococcus aureus and/or Group A streptococcus with azithromycin nonsusceptibility cultured from impetigo swabs.

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

Swab study outcome - Prevalence of bacterial carriage as assessed by real-time quantitative PCR (qPCR)

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)

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)

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

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

To compare the infant and maternal microbiome of specified body sites at key time points in the intervention and placebo groups

Full Information

NCT ID

NCT03925480

First Posted

April 4, 2019

Last Updated

April 25, 2023

Sponsor

Murdoch Childrens Research Institute

Collaborators

Ministry of Health, Fiji

1. Study Identification

Unique Protocol Identification Number

NCT03925480

Brief Title

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

Acronym

PreYIAL

Official Title

Preventing Young Infant Infections Using Azithromycin in Labour (PreYIAL): a Blinded, Randomised, Placebo-controlled Trial

Study Type

Interventional

2. Study Status

Record Verification Date

April 2023

Overall Recruitment Status

Completed

Study Start Date

July 1, 2019 (Actual)

Primary Completion Date

May 25, 2022 (Actual)

Study Completion Date

February 28, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Murdoch Childrens Research Institute

Collaborators

Ministry of Health, Fiji

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Bacterial Infections

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Model Description

Blinded, randomized, placebo-controlled trial

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

Matched drug and placebo

Allocation

Randomized

Enrollment

2110 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Azithromycin

Arm Type

Experimental

Arm Description

A single 2g dose of Azithromycin

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Matching Placebo

Intervention Type

Drug

Intervention Name(s)

Azithromycin 500 mg Oral Tablet x 4

Intervention Description

A single prophylactic dose of antibiotic given during labour

Intervention Type

Drug

Intervention Name(s)

Matching Placebo

Intervention Description

Matching Placebo

Primary Outcome Measure Information:

Title

Cumulative incidence of skin and soft tissue infection by 3 months of age in infants

Description

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.

Time Frame

3 months

Secondary Outcome Measure Information:

Title

Cumulative incidence of skin and soft tissue infection, and other infections by 12 months of age in infants

Description

Time Frame

Birth to 12 Months

Title

Cumulative incidence of maternal infection by 6 weeks and 12 months post-delivery

Description

Time Frame

Delivery to 12 months

Title

Cumulative incidence of antibiotic usage by 12 months in infants

Description

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;

Time Frame

Birth to 12 months

Title

Cumulative incidence of maternal antibiotic usage by 12 months post-delivery

Description

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

Time Frame

Delivery to 12 months

Title

Number of infant participants with adverse events as assessed by adapted version of CTCAE v5.0 and DAID v2.1

Description

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.

Time Frame

Birth to 12 months

Title

Number of maternal participants with adverse events as assessed by adapted version of CTCAE v5.0 and DAID v2.1

Description

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.

Time Frame

Delivery to 12 months

Title

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

Description

Time Frame

Delivery/birth to 12 months

Title

Number of infant and maternal participants with Staphylococcus aureus and/or Group A streptococcus with azithromycin nonsusceptibility cultured from impetigo swabs.

Description

Time Frame

Delivery/birth to 12 months

Title

Swab study outcome - Prevalence of bacterial carriage as assessed by real-time quantitative PCR (qPCR)

Description

Time Frame

Delivery/birth to 12 months

Title

Swab study outcome - Density of bacterial carriage as assessed by real-time quantitative PCR (qPCR)

Description

Time Frame

Delivery/birth to 12 months

Title

Swab study outcome - Risk of maternal carriage identified through qPCR of common organisms relevant to Sexually Transmitted Infections (STI)

Description

Time Frame

Delivery/birth to 6 months

Title

Swab study outcome - Risk of antibiotic nonsusceptibility in culture isolates

Description

Time Frame

Delivery/birth to 12 months

Title

Swab study outcome - The prevalence of infants with diagnoses that have been associated with microbiome dysbiosis

Description

To compare the infant and maternal microbiome of specified body sites at key time points in the intervention and placebo groups

Time Frame

Delivery/birth to 6 months

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion criteria: Pregnant women at least 18 years old intending to deliver at Colonial War Memorial Hospital (CWMH) Women who have been admitted to CWMH for delivery at the time of eligibility assessment Women who expect to be available, with their infant, for the duration of the study, and who agree to adhere to all protocol requirements 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 Women who have provided written informed consent prior to study-related procedures being performed Exclusion criteria: Women who have a known macrolide allergy Women who have taken antibiotics in the week prior to randomisation A women who is unable or unwilling to provide informed consent for her participation in the trial or the participation of her infant Women who decide prior to randomisation that they are no longer willing to participate or to have their infant participate Women who have ever received, or who are anticipated to receive during the study period, any investigational agent other than the study drug 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 Women taking warfarin due to the potential for drug interactions with azithromycin Women with any cardiac abnormality Women taking other medications known to prolong the QT interval such as antiarrhythmics; antipsychotic agents; antidepressants; and fluoroquinolones; Women with known electrolyte disturbances: including in cases of hypokalaemia and hypomagnesaemia Women who will undergo general anaesthetic for delivery Women carrying a foetus with intrauterine death confirmed before randomisation Women carrying a foetus with a prognosis unlikely to survive Women with known HIV infection and/or taking nelfinavir Women who have participated in the study during a previous pregnancy 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). Women with renal impairment Women with hepatic impairment Women with myasthenia gravis Women who are taking any ergot medications

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Fiona M Russell, BMBS PhD

Organizational Affiliation

Murdoch Childrens Research Institute

Official's Role

Principal Investigator

Facility Information:

Facility Name

Colonial War Memorial Hospital and Mother and Child Health Clinics

City

Suva

State/Province

Central

Country

Fiji

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

The de-identified data set collected for this analysis of the PreYIAL trial will be available six months after publication of the primary outcome. The study protocol, analysis plan and consent forms will also be available. The data may be obtained from the Murdoch Children's Research Institute by emailing

IPD Sharing Time Frame

From 6 months following publication of primary results for 15 years

IPD Sharing Access Criteria

Prior to releasing any data the following are required: a data access agreement must be signed between relevant parties, the DSMB must see and approve the analysis plan describing how the data will be analysed, there must be an agreement around appropriate acknowledgement and any additional costs involved must be covered. Data will only be shared with a recognised research institution which has approved the proposed analysis plan.

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

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