Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000753752
Ethics application status
Approved
Date submitted
5/04/2022
Date registered
26/05/2022
Date last updated
26/05/2022
Date data sharing statement initially provided
26/05/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Viral mitigation measures and preterm birth rate in high risk pregnant women
Scientific title
A pilot feasibility randomised controlled trial investigating the effect of viral transmission mitigation measures on the incidence of preterm birth in high-risk pregnant women.
Secondary ID [1] 306844 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record
Rolnik, D.L., Matheson, A., Liu, Y., Chu, S., Mcgannon, C., Mulcahy, B., Malhotra, A., Palmer, K.R., Hodges, R.J. and Mol, B.W. (2021), Impact of COVID-19 pandemic restrictions on pregnancy duration and outcome in Melbourne, Australia. Ultrasound Obstet Gynecol, 58: 677-687. https://doi.org/10.1002/uog.23743

The study was not registered in any trial registries given it was an observational, retrospective study. Our trial is a follow up to this study.

Health condition
Health condition(s) or problem(s) studied:
Preterm birth 325936 0
COVID-19 325937 0
Condition category
Condition code
Reproductive Health and Childbirth 323247 323247 0 0
Other reproductive health and childbirth disorders
Infection 323248 323248 0 0
Other infectious diseases
Public Health 323426 323426 0 0
Health service research

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The research team alongside research midwives will recruit pregnant women from the antenatal clinic at Monash Medical Centre who are high risk for having a preterm birth, where high risk will be defined as women who have had a previous preterm birth.

We will randomise these women to the 'intervention' and 'control' groups. The control group will undergo standard pregnancy care without any changes.

Women who are randomised to the 'intervention' group will be asked to comply with a set of viral mitigation measures, similar to those introduced in the in the stage 3 and 4 SARS-CoV-2 lockdowns in Melbourne, Australia.

Participants in the intervention group will be asked to comply with the following for the duration of the study:
1. Study participants should attempt to maintain social distancing where possible. They should refrain from leaving their homes unless required to do so,
such as shopping for essentials, to work or study, to seek/give care or for outside exercise. Study participants allocated to the intervention arm should
avoid having visitors to their home, unless it is their intimate partner. Study participants should try to maintain 1.5m distance between themselves and
another party unless in their own home or with an intimate partner.
2. Study participants will be instructed to wear a face mask/covering when outside their home and perform hand hygiene prior to removing their
mask/touching any aspect of their nose or mouth.
3. Study participants should aim to remain at home between the hours of 9pm and 5am unless they are required to leave for work/study or to seek/give
care, and should avoid travelling beyond 5km of their place of residence.

Participants will be recruited two weeks prior to the gestational age at which the study participant’s previous preterm birth occurred (i.e. if someone delivered in her previous pregnancy at 32+3 weeks, the intervention will start at 30+3 weeks). It will be conducted for six weeks (i.e two weeks prior and four weeks post the gestational age of the previous preterm birth) or until 34 weeks of gestation or until birth, whichever comes first.

Participants will be required to complete short surveys (which will be developed through Qualtrics XM) to assess their compliance with viral mitigation measures, activities, mood and quality of life at baseline and then on a fortnightly basis for the duration of the study.
Intervention code [1] 323305 0
Prevention
Comparator / control treatment
Women randomised to the control group will undergo standard pregnancy care without any changes. The research team will not ask them comply with any viral mitigation measures.

Standard pregnancy care involves between 2-4 weekly antenatal appointments, antenatal screening pathology (e.g serology testing, blood group, iron studies, vitamin D level), ultrasound scans, vaccinations (Pertussis, COVID-19 vaccination), growth scans if indicated in specific patient populations (e.g those with risk factors for fetal growth restriction), vaginal swabs (Group B Strep screening) etc.

We will ask them to complete fortnightly surveys to assess which viral mitigation measures they are still following of their own accord given the SARS-CoV-2 pandemic is still ongoing, mood, quality of life, sleep and other activities.
Control group
Active

Outcomes
Primary outcome [1] 330989 0
Primary Outcome: Feasibility of this study.
We will measure feasibility using the following criteria alongside targets that will establish whether a larger trial would be feasible to conduct:

Patient eligibility rate
o Measured as the proportion of eligible women screened at Monash Medical Centre’s Antenatal Clinics who are expected to consent to taking part in this trial
o We will set a target of at least 50%

Patient recruitment rate
o The proportion of eligible pregnant women who are recruited and randomized
o We will set a target of at least 50%

Compliance rate
o The proportion of participants in the intervention group who are considered to have good compliance with the intervention
o Compliance will be measured using subjective (fortnightly surveys) measures.
o We will set a target of at least 75%.

Data completion rate
o This will be measured as the proportion of final surveys completed (i.e the survey that is conducted after the end of the intervention)
o We will set a target of at least 75%.

Data will be collected from patient's medical recods and via fortnightly surveys conducted throughout the intervention period.
Timepoint [1] 330989 0
Patient eligibility rate
o This will be measured following the recruitment of 100 women to the study.

Patient recruitment rate
o This will be measured following the recruitment of 100 women to the study.

Compliance rate
o This will be measured via surveys at baseline (i.e before the participant begins the study) and then on a fortnightly basis until the end of the study.

Data completion rate
o This will be measured as the proportion of final surveys completed (i.e the survey that is conducted after the end of the study).
Secondary outcome [1] 408391 0
Incidence of preterm birth (<34 weeks)
Timepoint [1] 408391 0
This will be measured when the patient gives birth by accessing their medical records (data-linkage).

Secondary outcome [2] 409047 0
Maternal quality of life
Timepoint [2] 409047 0
This will be measured at baseline and then on a fortnightly basis throughout the intervention via surveys. The survey for this study was designed specifically for this study by the research team based on other validated pregnancy questionnaires including the Beck Depression Inventory , Edinburgh Postnatal Depression Scale, QOL GRAV, EQ-5D-3L and the Multidimensional Scale of Perceived Social Support.
Secondary outcome [3] 409048 0
Pregnancy duration
Timepoint [3] 409048 0
This will be measured following the birth of the baby by accessing the patient's medical records (data-linkage).
Secondary outcome [4] 409161 0
Incidence of stillbirth
Timepoint [4] 409161 0
This will be measured following the birth of the baby by accessing the patient's medical records (data-linkage).
Secondary outcome [5] 409162 0
Incidence of iatrogenic delivery
Timepoint [5] 409162 0
This will be measured following the birth of the baby by accessing the patient's medical records (data-linkage).
Secondary outcome [6] 409163 0
Incidence of spontaneous delivery
Timepoint [6] 409163 0
This will be measured following the birth of the baby by accessing the patient's medical records (data-linkage).
Secondary outcome [7] 409313 0
Incidence of admission to Special Care Nursery (SCN)
Timepoint [7] 409313 0
This will be measured following the birth of the baby by accessing the patient's medical records (data-linkage).
Secondary outcome [8] 409314 0
Birthweight
Timepoint [8] 409314 0
This will be measured following the birth of the baby by accessing the patient's medical records (data-linkage).
Secondary outcome [9] 409315 0
Newborn health assessed by 5 minute APGAR score
Timepoint [9] 409315 0
This will be measured following the birth of the baby by accessing the patient's medical records (data-linkage).
Secondary outcome [10] 409994 0
Incidence of admission to the neonatal intensive care unit (NICU)
Timepoint [10] 409994 0
This will be measured when the patient gives birth by accessing their medical records (data-linkage).
Secondary outcome [11] 409995 0
Incidence of Respiratory Distress Syndrome (RDS) requiring intubation
Timepoint [11] 409995 0
This will be measured after the patient gives birth by accessing their medical records (data-linkage).
Secondary outcome [12] 409996 0
Incidence of Interventrincular Haemorrhage (IVH)
Timepoint [12] 409996 0
This will be measured after the patient gives birth by accessing medical records (data linkage).
Secondary outcome [13] 409997 0
Incidence of neonatal seizures
Timepoint [13] 409997 0
This will be measured after the patient gives birth by accessing medical records (data linkage).
Secondary outcome [14] 409998 0
Incidence of culture-positive neonatal sepsis
Timepoint [14] 409998 0
This will be assessed after the patient gives birth by accessing medical records (data linkage).
Secondary outcome [15] 409999 0
Incidence of retinopathy of prematurity requiring treatment
Timepoint [15] 409999 0
This will be assessed after the patient gives birth by accessing medical records (data linkage).
Secondary outcome [16] 410000 0
Incidence of necrotizing enterocolitis
Timepoint [16] 410000 0
This will be assessed after the patient gives birth by accessing medical records (data linkage).
Secondary outcome [17] 410001 0
Incidence of neonatal death
Timepoint [17] 410001 0
This will be assessed after the patient gives birth by accessing medical records (data linkage).

Eligibility
Key inclusion criteria
Pregnant women (singleton or multiple gestation) who are at ‘high risk’ of having a preterm birth where ‘high-risk’ will be defined as pregnant women who have had a previous preterm birth (<34 weeks), either spontaneously or due to iatrogenic delivery.
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
We will exclude pregnant women carrying a foetus with one or more major congenital abnormalities.

We will exclude any pregnant women under the age of 18.

We will exclude pregnant women carrying a multiple gestation who have not had a previous preterm birth.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Participants will be randomized to either the intervention group, where they will be instructed to adhere to restriction measures initially imposed to mitigate Sars-CoV-2 transmission, or the control group where they will undergo standard pregnancy care. Randomization and allocation processes will be performed on the first day of the trial, through a computer-generated randomization list in RedCap. Redcap is a secure, web-based data collection and management software that meets Health Inurance Portability and Accountability Act (HIPAA) compliance standards.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomization and allocation processes will be performed on the first day of the trial, through a computer-generated randomization list in RedCap. Redcap is a secure, web-based data collection and management software that meets Health Inurance Portability and Accountability Act (HIPAA) compliance standards.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Given the primary objective of this trial is to establish feasibility, we will aim to recruit up to 100 ‘high-risk’ pregnant women, 50 of whom will be randomised to the intervention group and 50 of whom will be randomised to the control group.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
31/05/2022
Actual
Date of last participant enrolment
Anticipated
15/05/2023
Actual
Date of last data collection
Anticipated
30/06/2023
Actual
Sample size
Target
100
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 22137 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment postcode(s) [1] 37261 0
3168 - Clayton

Funding & Sponsors
Funding source category [1] 311170 0
Hospital
Name [1] 311170 0
Monash Medical Centre
Country [1] 311170 0
Australia
Primary sponsor type
Hospital
Name
Monash Medical Centre
Address
246 Clayton Rd
Clayton, Victoria 3168
Australia
Country
Australia
Secondary sponsor category [1] 312527 0
None
Name [1] 312527 0
None
Address [1] 312527 0
N/A
Country [1] 312527 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310700 0
Monash Health Human Research Ethics Committee
Ethics committee address [1] 310700 0
246 Clayton Rd, Clayton VIC 3168
Ethics committee country [1] 310700 0
Australia
Date submitted for ethics approval [1] 310700 0
23/02/2022
Approval date [1] 310700 0
16/03/2022
Ethics approval number [1] 310700 0
HREC/84541/MonH-2022-302345(v1)

Summary
Brief summary
On March 11th, 2020, the World Health Organization declared the outbreak of SARS-CoV-2 to be a pandemic. With case numbers rising sharply, Australian state and territory governments began introducing restriction measures including limitations on social gatherings, closure of non-essential services and social distancing rules with the aim of mitigating spread of the virus. The Victorian state government imposed a less stringent set of restrictions in March 2020, followed by a period of eased restricted and then a second, harsher set of restrictions in July 2020.

It has been observed that there has been a reduction in the rate of preterm birth in women exposed to restriction measures implemented to mitigate SARS-CoV-2 transmission; an effect that is more pronounced in women who have previously experienced a preterm birth.
We propose a two-arm randomized controlled feasibility clinical trial to be conducted in Monash Medical Centre (Melbourne, Australia). We will study pregnant women who are enrolled in the antenatal clinics and who have previously had a preterm birth (<34 weeks). Eligible participants will be randomized into two groups: the intervention group, where participants will be required to adhere to restriction measures originally imposed to mitigate transmission of the SARS-CoV-2 virus until birth or the control group, where participants will undergo standard pregnancy care.

The primary outcome of this trial will be feasibility, which will be assessed by measuring patient eligibility rate, recruitment rate, compliance rate and data completion rate. The secondary outcome measures of this trial will be the rate of preterm birth (<34 weeks), maternal quality of life and pregnancy outcomes. We will aim to recruit up to 100 pregnant women, 50 of whom will be randomized to the intervention and 50 of whom will be randomized to the control group.

The aim of this study is to establish feasibility and we acknowledge that the sample size is not significant enough to prove an effect on the rate of preterm birth. This study will establish a foundation upon which to conduct a larger randomized controlled trial, investigating the effects of restriction measures on the reduction of the rate of preterm birth and therefore play a role in preventing the significant health and economic consequences of preterm birth.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 118562 0
Prof Ben Mol
Address 118562 0
Monash Medical Centre
246 Clayton Rd, Clayton
Victoria 3168
Country 118562 0
Australia
Phone 118562 0
+61434122170
Fax 118562 0
Email 118562 0
ben.mol@monash.edu
Contact person for public queries
Name 118563 0
Dr Daniel Rolnik
Address 118563 0
Monash Health
246 Clayton Rd, Clayton
Victoria 3168
Country 118563 0
Australia
Phone 118563 0
+61452105585
Fax 118563 0
Email 118563 0
daniel.rolnik@monash.edu
Contact person for scientific queries
Name 118564 0
Dr Daniel Rolnik
Address 118564 0
Monash Health
246 Clayton Rd, Clayton
Victoria 3168
Country 118564 0
Australia
Phone 118564 0
+61452105585
Fax 118564 0
Email 118564 0
daniel.rolnik@monash.edu

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
In order to protect the confidentiality of participants, we will only present whole group data.


What supporting documents are/will be available?

Current supporting documents:
Doc. No.TypeCitationLinkEmailOther DetailsAttachment
15685Study protocol    383876-(Uploaded-24-05-2022-19-21-24)-Study-related document.docx
15686Informed consent form    383876-(Uploaded-05-04-2022-11-48-28)-Study-related document.docx
15687Ethical approval    383876-(Uploaded-05-04-2022-11-48-45)-Study-related document.pdf


Updated to:
Doc. No.TypeCitationLinkEmailOther DetailsAttachment
15685Study protocol    383876-(Uploaded-16-11-2023-21-11-41)-Study-related document.docx
15686Informed consent form    383876-(Uploaded-16-11-2023-21-13-21)-Study-related document.docx
15687Ethical approval    383876-(Uploaded-05-04-2022-11-48-45)-Study-related document.pdf

Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
Dimensions AIFeasibility of a pregnancy intervention mimicking viral transmission mitigation measures on the incidence of preterm birth in high-risk pregnant women enrolled in antenatal clinics in Melbourne, Australia: protocol for a pilot, randomised trial2023https://doi.org/10.1136/bmjopen-2023-075703
N.B. These documents automatically identified may not have been verified by the study sponsor.