Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001450707
Ethics application status
Approved
Date submitted
4/10/2022
Date registered
14/11/2022
Date last updated
14/11/2022
Date data sharing statement initially provided
14/11/2022
Type of registration
Retrospectively registered

Titles & IDs
Public title
Investigating the use of biomarkers to predict pregnancy and long term complications in women who develop elevated blood pressure, gestational diabetes, fetal growth restriction or spontaneous preterm labour during pregnancy
Scientific title
Investigating the use of biomarkers to predict pregnancy and long term cardiovascular complications in women who develop elevated blood pressure, gestational diabetes, fetal growth restriction or spontaneous preterm labour during pregnancy
Secondary ID [1] 307916 0
Nil known
Universal Trial Number (UTN)
Trial acronym
BIOPIC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
pre-eclampsia 327562 0
Gestational Diabetes 327563 0
Spontaneous preterm birth 327564 0
Fetal growth restriction 327565 0
Condition category
Condition code
Reproductive Health and Childbirth 324653 324653 0 0
Antenatal care
Reproductive Health and Childbirth 325065 325065 0 0
Fetal medicine and complications of pregnancy
Reproductive Health and Childbirth 325233 325233 0 0
Complications of newborn

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
This observational study does not include any intervention to routine medical care of the participant.
Participation will involve completion of a questionnaire and collection of 3 blood samples.
The questionnaire will have questions regarding basic demographic information, past medical history, details of previous pregnancy/pregnancies (gestational age at delivery, complications during pregnancy, any antenatal interventions, mode of delivery and birth weight), as well as details of current pregnancy (pregnancy complications, antenatal interventions). This will take 10-15min to complete.
Blood samples will be collected once at time of recruitment, once at development of complications or at 36 weeks gestations, and finally at 6 months post birth.
For this study we will also be collecting de-identified data from participant's medical records. This include demographic details, past medical history, antenatal complications, antenatal interventions, mode of delivery and any peri-partum complications.
The total observational period will be from time of recruitment (at any gestation of pregnancy) until 6 months post delivery.
Intervention code [1] 324546 0
Diagnosis / Prognosis
Comparator / control treatment
The comparator will be participants who are recruited after meeting eligibility criteria (blood pressure >130/80) who have not developed and does not go on to develop any pregnancy complications (hypertension in pregnancy, gestational diabetes, fetal growth restriction, spontaneous preterm birth).
For this group, blood samples will be collected at time of recruitment and at 36 weeks gestation.
Control group
Active

Outcomes
Primary outcome [1] 332678 0
Women with demographic or examination (e.g. elevated BP >=130/80) risk factors who go on to develop pre-eclampsia by current diagnostic criteria of pre-eclampsia (blood pressure >140/90 with evidence of end organ dysfunction).
This will be determined by review of medical records and pathology results. As well as by patient self reporting.
Timepoint [1] 332678 0
This outcome will be determined through weekly review of participant's medical record from time of recruitment until birth to identify the development of pre-eclampsia. Or at any time during this period by patient self report.
Primary outcome [2] 332893 0
Women with pregnancy complications (Gestational diabetes, hypertensive disorder of pregnancy, fetal growth restriction and spontaneous preterm birth) who have persistent derangement in cardio-metabolic markers (HbA1c, Insulin levels, BNP, Lipid profile) 6-12 months post-partum. This will be assessed using blood samples.
Timepoint [2] 332893 0
This outcome will be assessed through blood samples which will be collected once at time of recruitment, once at development of complications or at 36 weeks gestations, and once at 6-12 months post-partum at the convenience of the participant.
Primary outcome [3] 333079 0
Women with elevated blood pressures (>130/80) and/or pregnancy complications (Gestational diabetes, hypertensive disorder of pregnancy, fetal growth restriction and spontaneous preterm birth) who have derangement in placental markers (sFlt, PLGF, sFlt/PLGF ratio), assessed using blood samples.
Timepoint [3] 333079 0
his outcome will be assessed through blood samples which will be collected once at time of recruitment, once at development of complications or at 36 weeks gestations, and once at 6-12 months post-partum at the convenience of the participant.
Secondary outcome [1] 414340 0
Adverse maternal outcomes: This will include a composite of hepatic dysfunction, acute renal insufficiency, placental abruption, acute pulmonary oedema, development of HELLP (Haemolysis, elevated liver enzymes, low platelets) syndrome, need for parenteral antihypertensive medication, need for insulin therapy, admission to intensive care unit, mode of delivery and postpartum haemorrhage.
These outcomes will be assessed by review of participant medical records.
Timepoint [1] 414340 0
This outcome will be determined through review of participant's medical record from the time of enrolment to the time of delivery.
Secondary outcome [2] 415001 0
Adverse perinatal outcomes: This will include a composite of gestation at delivery, birth weight, stillbirth, neonatal death and neonatal morbidity. Neonatal morbidity will be defined as admission to a neonatal special care nursery or intensive care unit for more than 48 hours, respiratory distress syndrome, need for mechanical ventilation, intraventricular haemorrhage, confirmed infection, necrotising enterocolitis, seizures, encephalopathy and retinopathy of prematurity.
Incidence of these perinatal outcomes will be assessed through review of the of participant's newborn's medical records.
Timepoint [2] 415001 0
This outcome will be determined through review of participant's baby's medical record from time of delivery to 28 days after birth.
Secondary outcome [3] 415721 0
Women with elevated blood pressures (>130/80) and/or pregnancy complications (Gestational diabetes, hypertensive disorder of pregnancy, fetal growth restriction and spontaneous preterm birth) who have derangement in endothelial dysfunction markers (ICAM 1, VCAM 1, tumor necrosis factor-alpha) assessed using blood samples
Timepoint [3] 415721 0
This outcome will be assessed through blood samples which will be collected once at time of recruitment, once at development of complications or at 36 weeks gestations, and once at 6-12 months post-partum at the convenience of the participant.

Eligibility
Key inclusion criteria
1. Pregnant women at any gestation in pregnancy AND
2. Women who develop elevated blood pressure >130/80 OR
3. Women who have developed pregnancy complications (Gestational diabetes (GDM), Hypertensive disorder of pregnancy (HDP), Fetal growth restriction(FGR) and spontaneous preterm birth(sPTB))
Minimum age
18 Years
Maximum age
55 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Multiple pregnancy.
2. Pregnancy complicated by major fetal anomaly or genetic syndrome.
3. Maternal age less than 18 years,
4. Women incapable of giving valid consent (diminished understanding, non-English speaking
and interpreter unavailable).
5. Participation in a study where there is a pharmaceutical intervention that would likely modify the biomarkers under study.

Study design
Purpose
Screening
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
For comparison between groups, t-test and/or Mann-Whitney test and binary logistic regression will be used, as appropriate. To test and adjust for potential confounders, logistic regression analysis will be performed. Screening performance will be assessed using sensitivity, specificity, positive and negative predictive values and Receiver Operating Curve (ROC) areas. The analysis will be carried out using SPSS 16.0 (SPSS Inc., Chicago, IL) and Stata (version 12 or later; StataCorp, College Station, Texas, USA). The study will be reported in accordance with STAndards for the Reporting of Diagnostic accuracy studies (STARD) guidelines.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
3/10/2022
Date of last participant enrolment
Anticipated
3/10/2024
Actual
Date of last data collection
Anticipated
31/12/2025
Actual
Sample size
Target
600
Accrual to date
1
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 23280 0
Dandenong Hospital- Monash Health - Dandenong
Recruitment hospital [2] 23281 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [3] 23282 0
Casey Hospital - Berwick
Recruitment postcode(s) [1] 38653 0
3168 - Clayton
Recruitment postcode(s) [2] 38652 0
3175 - Dandenong
Recruitment postcode(s) [3] 38654 0
3806 - Berwick

Funding & Sponsors
Funding source category [1] 312189 0
University
Name [1] 312189 0
Monash University
Country [1] 312189 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
National Heart Foundation
Address
2/850 Collins St, Melbourne VIC 3008
Country
Australia
Secondary sponsor category [1] 313718 0
Government body
Name [1] 313718 0
NHMRC
Address [1] 313718 0
414 La Trobe St, Melbourne VIC 3000
Country [1] 313718 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311576 0
Monash Health HREC
Ethics committee address [1] 311576 0
Level 2, I Block
Monash Medical Centre 246 Clayton Road
Clayton Victoria 3168
Ethics committee country [1] 311576 0
Australia
Date submitted for ethics approval [1] 311576 0
06/04/2022
Approval date [1] 311576 0
09/08/2022
Ethics approval number [1] 311576 0
RES-22-0000-197A

Summary
Brief summary
Purpose of study:
In Australia, up to 1 in 20 women will have a pregnancy impacted by pre-eclampsia, however recent changes to the definition of high blood pressure may assist in finding women most at risk earlier in their pregnancy. This study will explore a new approach to diagnosing pre-eclampsia that could benefit women in the future.
Similarly, a third of women are affected by cardio-metabolic conditions during pregnancy such as gestational diabetes (GDM), pregnancy induced hypertension, pre-eclampsia, fetal growth restriction and spontaneous preterm birth. These conditions not only cause significant morbidity during pregnancy but are also associated with increased risk of maternal Type 2 Diabetes and Cardiovascular Disease (CVD) after pregnancy.
However, CVD risk prediction tools do not capture these pregnancy-related cardio-metabolic conditions. Younger women and their health professionals have a limited understanding of the risks and screening and prevention are generally lacking.
We know that these risks can be reduced by preventative screening (such as early screening for diabetes, abnormal lipid levels or elevated blood pressure) and optimising lifestyle strategies. This study offers an important opportunity to identify and target these women at risk for early intervention and screening.

Hypothesis:
Biological markers of endothelial, placental, inflammatory and cardiac dysfunction can be used to create an algorithm that can better predict the risk of developing pre-eclampsia, as well as risk of long-term cardiovascular sequelae in patients affected by pregnancy complications. Evidenced by derangement in cardio-metabolic markers following development of these conditions which persists post-delivery.

Study design:
Prospective observational trial involving two blood collection during pregnancy as well as after delivery. Where possible these blood test would be performed at time of routine pathology collection. Blood test result of patient who develops complication and those who does not is compared to develop an algorithm for prediction and diagnosis of pregnancy complications, as well as evaluate risk of long term cardiovascular complications. This study is observational only and does not interfere with routine antenatal care.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 121582 0
A/Prof Kirsten Palmer
Address 121582 0
Monash University
246 Clayton Road, Clayton VIC 3168
Country 121582 0
Australia
Phone 121582 0
+61419846049
Fax 121582 0
Email 121582 0
kirsten.palmer@monash.edu
Contact person for public queries
Name 121583 0
Dr Amy Liu
Address 121583 0
Monash University
246 Clayton Road, Clayton VIC 3168
Country 121583 0
Australia
Phone 121583 0
+61 395946666
Fax 121583 0
Email 121583 0
amy.liu1@monash.edu
Contact person for scientific queries
Name 121584 0
Dr Amy Liu
Address 121584 0
Monash University
246 Clayton Road, Clayton VIC 3168
Country 121584 0
Australia
Phone 121584 0
+61 395946666
Fax 121584 0
Email 121584 0
amy.liu1@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


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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

Documents added automatically
No additional documents have been identified.