Clinical trial NCT04412681: Precision Medicine for Prediction & Prevention of Early Pre-eclampsia
Official title: Using Precision Medicine for the Prediction and Prevention of Early Pre-eclampsia: A Feasibility Study at Sunnybrook Health Sciences Centre.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Pre-Eclampsia
Lead sponsor: Sunnybrook Health Sciences Centre
Sponsor class: OTHER
Collaborators: name: North York General Hospital
First posted: 2020-06-02
Enrollment: 1000
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: This study aims to evaluate the feasibility of implementing a clinical model for precision screening of early pre-eclampsia into the current prenatal screening service at Sunnybrook Health Sciences Center (SHSC).

Detailed description: Pre-eclampsia (PE) represents a pregnancy-specific systemic disorder that affects 3-8% of all pregnancies. In developed countries PE is considered a major public health problem responsible for severe maternal complications such as coagulopathy, renal and liver failure, stroke, and maternal death (\>76,000 maternal death annually).

The traditional approach to screening for preeclampsia endorsed by national guidelines is based on a combination of maternal characteristics along with medical, obstetric and family history.

However, although these methods are simple and easy to perform, maternal factors can only identify less than 35% of all preeclampsia and approximately 40% of preterm-preeclampsia at a false- positive rate of 10%.

More recently, multivariate analysis has been used to develop predictive models for preeclampsia that can be applied as early as 11-13+6 weeks gestation. One such algorithm, developed by the Fetal Medicine Foundation UK(MFM UK), incorporates maternal risk factors, uterine artery doppler, mean arterial pressure, and serum markers of placental function and placental growth factor. The FMFUK algorithm has been shown to predict approximately 75-90% of those women destined to develop preeclampsia prior to 37 and 34 weeks respectively, at a false positive rate of 10%. This algorithm has been validated prospectively in several studies, including the prediction of other placental mediated complications of pregnancy, such as fetal growth restriction and perinatal death.

The new clinical model will include the following additions to the existing first trimester screening for aneuploidy:

* Additional Clinical History
* Blood pressure measurements
* Ultrasound for uterine artery Doppler measurements
* Expanded prenatal screening requisition
* Quality assurance training of ultrasound technicians for the uterine artery doppler measurements
* Fetal Medicine Foundation validated risk calculation algorithm
* Communicate results of the risk calculation algorithm from NYGH to SHSC and participant health care providers.

While the ultimate goal will be to scale up and adapt this new clinical model, this protocol focuses on the feasibility of implementing the new clinical model at a single centre, Sunnybrook Health Sciences Centre.

Eligibility criteria: Inclusion Criteria:

1. Women with a singleton pregnancy \> 18 years old
2. Not on low dose aspirin
3. Carrying a live fetus with crown rump length (CRL) between 41 and 84mm
4. Able to provide informed consent
5. Having a nuchal translucency ultrasound

Exclusion Criteria:

1. Women with a singleton pregnancy \< 18 years old
2. Women currently taking low dose aspirin
3. Women declining a nuchal translucency ultrasound
4. Women unable to provide informed consent
5. Women with a multiple pregnancy
6. Women with a demised fetus or a CRL \<41mm and \>84mm

Primary outcomes:
measure: Feasibility of Screening Tool
timeFrame: 11.3-13.6 weeks gestation
Secondary outcomes:
measure: Accuracy of Screening
timeFrame: 11.3-13.6 weeks gestation
measure: Acceptability of Screening Tool to Participants
timeFrame: 11.3-13.6 weeks gestation
measure: Compliance with low dose ASA for screen positive participants.
timeFrame: 16-36 weeks gestation
Other outcomes:
measure: Duration of the assessment
timeFrame: 11.3-13.6 weeks gestation
measure: Turnaround time from assessment to results
timeFrame: 11.3-16 weeks gestation
measure: Participant Satisfaction
timeFrame: 11.3-40 weeks gestation
Locations:
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences center
state: Ontario
Study officials:
affiliation: Sunnybrook Health Sciences Center
name: Ronzoni
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wright D, Syngelaki A, Akolekar R, Poon LC, Nicolaides KH. Competing risks model in screening for preeclampsia by maternal characteristics and medical history. Am J Obstet Gynecol. 2015 Jul;213(1):62.e1-62.e10. doi: 10.1016/j.ajog.2015.02.018. Epub 2015 Feb 25.
citation: O'Gorman N, Wright D, Poon LC, Rolnik DL, Syngelaki A, de Alvarado M, Carbone IF, Dutemeyer V, Fiolna M, Frick A, Karagiotis N, Mastrodima S, de Paco Matallana C, Papaioannou G, Pazos A, Plasencia W, Nicolaides KH. Multicenter screening for pre-eclampsia by maternal factors and biomarkers at 11-13 weeks' gestation: comparison with NICE guidelines and ACOG recommendations. Ultrasound Obstet Gynecol. 2017 Jun;49(6):756-760. doi: 10.1002/uog.17455.
citation: Park FJ, Leung CH, Poon LC, Williams PF, Rothwell SJ, Hyett JA. Clinical evaluation of a first trimester algorithm predicting the risk of hypertensive disease of pregnancy. Aust N Z J Obstet Gynaecol. 2013 Dec;53(6):532-9. doi: 10.1111/ajo.12126. Epub 2013 Aug 6.
citation: Mosimann B, Pfiffner C, Amylidi-Mohr S, Risch L, Surbek D, Raio L. First trimester combined screening for preeclampsia and small for gestational age - a single centre experience and validation of the FMF screening algorithm. Swiss Med Wkly. 2017 Aug 25;147:w14498. doi: 10.4414/smw.2017.14498. eCollection 2017.
citation: O'Gorman N, Wright D, Poon LC, Rolnik DL, Syngelaki A, Wright A, Akolekar R, Cicero S, Janga D, Jani J, Molina FS, de Paco Matallana C, Papantoniou N, Persico N, Plasencia W, Singh M, Nicolaides KH. Accuracy of competing-risks model in screening for pre-eclampsia by maternal factors and biomarkers at 11-13 weeks' gestation. Ultrasound Obstet Gynecol. 2017 Jun;49(6):751-755. doi: 10.1002/uog.17399. Epub 2017 May 14.
citation: Ananth CV, Keyes KM, Wapner RJ. Pre-eclampsia rates in the United States, 1980-2010: age-period-cohort analysis. BMJ. 2013 Nov 7;347:f6564. doi: 10.1136/bmj.f6564.