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

Pre-Eclampsia Clinical Trial

— FORECAST  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03941886
• Other study ID #: 2018-0434
• Status: Completed
• Phase: N/A
• Start date: July 31, 2019
• Est. completion date: August 15, 2023

Study information

• Verified date: November 2023
• Source: Chinese University of Hong Kong
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42454
• Est. completion date: August 15, 2023
• Est. primary completion date: June 15, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Eclampsia
• Pre-Eclampsia

Intervention

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

Locations

Country	Name	City	State
China	Guangzhou Women and Children's Medical Center	Guangzhou
China	Kunming Angel Women & Children Hospital	Kunming
China	Nanjing Drum Tower Hospital	Nanjing
Hong Kong	Kwong Wah Hospital	Hong Kong
Hong Kong	Prince of Wales Hospital	Hong Kong	Hong Kong, China
Indonesia	Harapan Kita Hospital	Jakarta
Japan	Clinical Research Institute of Fetal Medicine	Osaka
Japan	Showa University Hospital	Tokyo
Japan	Japan Society for the Study of Hypertension in Pregnancy	Toyama
Malaysia	Pusat Perubatan Universiti Kebangsaan Malaysia (UKM) Medical Centre	Bandar Tun Razak
Philippines	Philippine General Hospital	Manila
Singapore	National University Hospital	Singapore
Taiwan	Chang Gung Hospital	Taipei
Taiwan	Taiji Clinic	Taipei
Thailand	Chulalongkorn University Hospital	Bangkok
Thailand	Siriraj Hospital	Bangkok
Thailand	Maharaj Nakorn Chiang Mai Hospital	Chiang Mai
Thailand	Thammasat University Hospital	Khlong Luang
Vietnam	Hanoi Obstetrics & Gynecology Hospital	Hanoi

Sponsors (1)

Lead Sponsor	Collaborator
Chiu Yee Liona Poon

Countries where clinical trial is conducted

China,  Hong Kong,  Indonesia,  Japan,  Malaysia,  Philippines,  Singapore,  Taiwan,  Thailand,  Vietnam, 

References & Publications (13)

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. — View Citation

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. — View Citation

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. No abstract available. — View Citation

Khan KS, Wojdyla D, Say L, Gulmezoglu 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. — View Citation

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. Available from http://www.ncbi.nlm.nih.gov/books/NBK62652/ — View 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. Erratum In: Ultrasound Obstet Gynecol. 2017 Dec;50(6):807. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. No abstract available. — View 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. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Delivery with preterm-preeclampsia	Proportions of delivery with preterm preeclampsia between non-intervention and intervention groups	Before 37 weeks of gestation
Secondary	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
Secondary	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)
Secondary	Low birth weight	Low birth weight <3rd, 5th and 10th percentile	at birth
Secondary	Stillbirth	Fetal death at or after 20 to 28 weeks of pregnancy	at or after 20 to 28 weeks of pregnancy
Secondary	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
Secondary	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)
Secondary	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
Secondary	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)
Secondary	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)
Secondary	Gestational age at delivery	Gestational age at delivery	at delivery