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

Overview

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.

Full Title of Study: “Implementation of First-trimester Screening and Prevention of Preeclampsia: a Stepped Wedge Cluster-randomized Trial in Asia”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Sequential Assignment
    • Primary Purpose: Prevention
    • Masking: None (Open Label)
  • Study Primary Completion Date: December 2022

Interventions

  • Other: Low-dose aspirin in women with high risk of preeclampsia
    • 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

Arms, Groups and Cohorts

  • No Intervention: Non-intervention group
    • Participants receive routine prenatal care
  • Experimental: Intervention group
    • 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.

Clinical Trial Outcome Measures

Primary Measures

  • Delivery with preterm-preeclampsia
    • Time Frame: Before 37 weeks of gestation
    • Proportions of delivery with preterm-preeclampsia between non-intervention and intervention groups

Secondary Measures

  • Adverse outcomes with delivery at <34, <37 and ≥37 weeks of gestation
    • Time Frame: at <34, <37 and ≥37 weeks of gestation
    • including preeclampsia, gestational hypertension, small for gestational age birth weight (<5th percentile), stillbirth, placental abruption
  • Neonatal mortality
    • Time Frame: during the first 28 days of life (0-27 days)
    • 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.
  • Low birth weight
    • Time Frame: at birth
    • Low birth weight <3rd, 5th and 10th percentile
  • Stillbirth
    • Time Frame: at or after 20 to 28 weeks of pregnancy
    • Fetal death at or after 20 to 28 weeks of pregnancy
  • Spontaneous preterm birth
    • Time Frame: At <34 and <37 weeks’ gestation
  • The willingness of subjects accept to receive preeclampsia screening under the Bayes based method
    • Time Frame: in the first trimester of pregnancy (11-13 weeks of gestation)
    • 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.
  • The willingness of high-risk subjects to accept aspirin treatment
    • Time Frame: from <15 weeks till 36 weeks of gestation or, in the event of early delivery, at the onset of labor
    • 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.
  • Composite neonatal morbidity
    • Time Frame: during the first 28 days of life (0-27 days)
    • 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
    • Time Frame: during the first 28 days of life (0-27 days)
    • Neonatal high dependency or intensive care unit admission; Ventilation – need of positive pressure or intubation.

Participating in This Clinical Trial

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).

Gender Eligibility: Female

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Chiu Yee Liona Poon
  • Provider of Information About this Clinical Study
    • Sponsor-Investigator: Chiu Yee Liona Poon, Professor (Clinical) – Chinese University of Hong Kong
  • Overall Official(s)
    • Liona CY Poon, MD, Principal Investigator, Chinese University of Hong Kong
  • Overall Contact(s)
    • Liona CY Prof Poon, MD, (852) 3505 2582, liona.poon@cuhk.edu.hk

References

Geographic variation in the incidence of hypertension in pregnancy. World Health Organization International Collaborative Study of Hypertensive Disorders of Pregnancy. Am J Obstet Gynecol. 1988 Jan;158(1):80-3.

Steegers EA, von Dadelszen P, Duvekot JJ, Pijnenborg R. Pre-eclampsia. Lancet. 2010 Aug 21;376(9741):631-44. doi: 10.1016/S0140-6736(10)60279-6. Epub 2010 Jul 2. Review.

Khan KS, Wojdyla D, Say L, Gülmezoglu AM, Van Look PF. WHO analysis of causes of maternal death: a systematic review. Lancet. 2006 Apr 1;367(9516):1066-1074. doi: 10.1016/S0140-6736(06)68397-9. Review.

Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists' Task Force on Hypertension in Pregnancy. Obstet Gynecol. 2013 Nov;122(5):1122-1131. doi: 10.1097/01.AOG.0000437382.03963.88.

Tranquilli AL, Dekker G, Magee L, Roberts J, Sibai BM, Steyn W, Zeeman GG, Brown MA. The classification, diagnosis and management of the hypertensive disorders of pregnancy: A revised statement from the ISSHP. Pregnancy Hypertens. 2014 Apr;4(2):97-104. doi: 10.1016/j.preghy.2014.02.001. Epub 2014 Feb 15.

National Collaborating Centre for Women's and Children's Health (UK). Hypertension in Pregnancy: The Management of Hypertensive Disorders During Pregnancy. London: RCOG Press; 2010 Aug.

Committee Opinion No. 638: First-Trimester Risk Assessment for Early-Onset Preeclampsia. Obstet Gynecol. 2015 Sep;126(3):e25-e27. doi: 10.1097/AOG.0000000000001049. Review.

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.

O'Gorman N, Wright D, Syngelaki A, Akolekar R, Wright A, Poon LC, Nicolaides KH. Competing risks model in screening for preeclampsia by maternal factors and biomarkers at 11-13 weeks gestation. Am J Obstet Gynecol. 2016 Jan;214(1):103.e1-103.e12. doi: 10.1016/j.ajog.2015.08.034. Epub 2015 Aug 19.

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. Erratum in: Ultrasound Obstet Gynecol. 2017 Dec;50(6):807.

Rolnik DL, Wright D, Poon LC, O'Gorman N, Syngelaki A, de Paco Matallana C, Akolekar R, Cicero S, Janga D, Singh M, Molina FS, Persico N, Jani JC, Plasencia W, Papaioannou G, Tenenbaum-Gavish K, Meiri H, Gizurarson S, Maclagan K, Nicolaides KH. Aspirin versus Placebo in Pregnancies at High Risk for Preterm Preeclampsia. N Engl J Med. 2017 Aug 17;377(7):613-622. doi: 10.1056/NEJMoa1704559. Epub 2017 Jun 28.

Plasencia W, Maiz N, Poon L, Yu C, Nicolaides KH. Uterine artery Doppler at 11 + 0 to 13 + 6 weeks and 21 + 0 to 24 + 6 weeks in the prediction of pre-eclampsia. Ultrasound Obstet Gynecol. 2008 Aug;32(2):138-46. doi: 10.1002/uog.5402.

Poon LC, Zymeri NA, Zamprakou A, Syngelaki A, Nicolaides KH. Protocol for measurement of mean arterial pressure at 11-13 weeks' gestation. Fetal Diagn Ther. 2012;31(1):42-8. doi: 10.1159/000335366. Epub 2012 Jan 13.

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