Implementation of First-trimester Screening and preventiOn of pREeClAmpSia Trial (FORECAST)

Study Overview
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Brief Summary
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This implementation study aims to evaluate the efficacy, acceptability, and safety of first-trimester screening and prevention for preterm-preeclampsia. It is a multicenter stepped wedge cluster randomized trial including maternity / diagnostic units from ten regions in Asia. The study involves a period where no intervention will take place at all recruiting units, and then at regular intervals, one cluster will be randomized to transit from non-intervention group to intervention group in which first-trimester screening for preterm-preeclampsia by the Bayes based method followed by the commencement of low-dose aspirin in high-risk women.

Official Title
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Implementation of First-trimester Screening and Prevention of Preeclampsia: a Stepped Wedge Cluster-randomized Trial in Asia

Conditions
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Pre-Eclampsia

Intervention / Treatment
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* Other: Low-dose aspirin in women with high risk of preeclampsia


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Singleton pregnancy; Live fetus; Exclusion Criteria: Multiple pregnancy; Major fetal defects identified at 11-13 weeks of assessment; Non-viable fetus (missed spontaneous abortion or stillbirth).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: This is a stepped wedge cluster-randomized trial. There are total of 7 clusters across Asia. This study involves a period where no intervention will take place at all recruiting units, i.e. routine prenatal care, and then at regular intervals (every 6 weekly), one cluster will be randomized to transit from non-intervention group to intervention group in which first-trimester screening for preterm-preeclampsia by the Bayes based method followed by commencement of low-dose aspirin prophylaxis for high-risk women.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Non-intervention group<br>Participants receive routine prenatal care | |
| Experimental: Intervention group<br>Participants receive first-trimester screening for preterm-preeclampsia by the Bayes based method followed by commencement of low-dose aspirin prophylaxis in high-risk women. | Other: Low-dose aspirin in women with high risk of preeclampsia<br>* Low-dose aspirin 150-162 mg/night or 100 mg/night if body weight <40 Kg, from <15 weeks till 36 weeks or, in the event of early delivery, at the onset of labor<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Delivery with preterm-preeclampsia | Proportions of delivery with preterm preeclampsia between non-intervention and intervention groups | Before 37 weeks of gestation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse outcomes with delivery at <34, <37 and ≥37 weeks of gestation | including preeclampsia, gestational hypertension, small for gestational age birth weight (<5th percentile), stillbirth, placental abruption | at <34, <37 and ≥37 weeks of gestation | 
| Neonatal mortality | A neonatal death is a death during 0-27 days of life. Composite neonatal morbidity (any one of the following): > grade II intraventricular hemorrhage; neonatal sepsis confirmed by cultures; neonatal anemia requiring transfusion; respiratory distress syndrome requiring surfactant and ventilation; necrotising enterocolitis requiring surgical intervention. Composite neonatal therapy (any one of the following): Neonatal high dependency or intensive care unit admission; Ventilation - need of positive pressure or intubation. | during the first 28 days of life (0-27 days) | 
| Low birth weight | Low birth weight <3rd, 5th and 10th percentile | at birth | 
| Stillbirth | Fetal death at or after 20 to 28 weeks of pregnancy | at or after 20 to 28 weeks of pregnancy | 
| Spontaneous preterm birth | Spontaneous preterm birth (SPB) includes preterm labor, preterm spontaneous rupture of membranes, preterm premature rupture of membranes (PPROM) and cervical weakness; it does not include indicated preterm delivery for maternal or fetal conditions. | At <34 and <37 weeks' gestation | 
| Acceptability for PE screening | If subjects are under the intervention group upon proper consent procedure is done, at 11-13 weeks of gestation, the procedures below will be done. Collection of maternal information (obstetrical, medical and drug history including aspirin intake with indication) Measurement of maternal MAP and UtA-PI will be measured according to standardized protocols. Blood sample will be drawn to determine of serum level of PIGF. The individual study participant's risk of preterm-PE will be computed using the Bayes based method. | in the first trimester of pregnancy (11-13 weeks of gestation) | 
| Acceptability for aspirin treatment. | When patients are subjected to be high risks in preeclampsia screening, they will be asked if they accept the aspirin for treatment. If they do not accept, they will continue with routine care. The willingness of subjects will all be recorded on the Case report forms for data collection. | from <15 weeks till 36 weeks of gestation or, in the event of early delivery, at the onset of labor | 
| Composite neonatal morbidity | Composite neonatal morbidity (any one of the following): > grade II intraventricular hemorrhage; neonatal sepsis confirmed by cultures; neonatal anemia requiring transfusion; respiratory distress syndrome requiring surfactant and ventilation; necrotising enterocolitis requiring surgical intervention. | during the first 28 days of life (0-27 days) | 
| Composite neonatal therapy | Composite neonatal therapy (any one of the following): Neonatal high dependency or intensive care unit admission; Ventilation - need of positive pressure or intubation. | during the first 28 days of life (0-27 days) | 
| Gestational age at delivery | Gestational age at delivery | at delivery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pre-Eclampsia, Aspirin