COmputerized CTG Self-MOnitoring Versus Standard Doppler Assessment in Late-onset FGR: COSMOS Study (COSMOS)

COmputerized CTG Self-MOnitoring Versus Standard Doppler Assessment in Late-onset FGR: Study Protocol for a Randomized Controlled Trial

Fetal growth restriction is one of the major causes of perinatal morbidity, mortality and adverse neurological outcome. Growth restricted fetuses do not reach their potential due to multiple factors. Although early (<32 weeks' gestation) FGR is associated with the highest risk of adverse outcomes, late FGR (≤ 32 weeks' gestation) is more common in daily maternal-fetal medicine care. Despite its' prevalence, optimal standard for monitoring differs between the centers and may be difficult in case of limited access to advanced perinatal care. We present a protocol for COmputerized CTG Self-MOnitoring versus Standard Doppler assessment in Late-onset FGR (COSMOS) trial, which is a prospective, cross-over, open-label and randomized trial that compares two different protocols for late-onset FGR observation.

All women carrying fetuses with late-onset FGR with positive end-diastolic flow in umbilical artery will be invited to participate in the randomized trial. Patients will be randomly divided into two groups: CTG - a group that will receive electronic device for cCTG home assessment, and Doppler - a group that will be monitored according to standard Doppler velocimetry criteria. Further management will depend on the arm of the study. Pregnancy and neonatal outcomes will be collected and analyzed.

Study Overview

• Status: Recruiting
• Conditions: Fetal Growth Restriction
• Intervention / Treatment: Device: cCTG; Diagnostic test: Doppler

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Urszula Nowacka, MD; Phone Number: +48223277044; Email: ulasarzynska@gmail.com; urszula.nowacka@imid.med.pl
• Study Contact Backup: Name: Tadeusz Issat, Professor; Phone Number: +48223277044; Email: tadeusz.issat@imid.med.pl

Study Locations

• Poland
  • Warsaw, Poland, 01-211
    • Recruiting
    • Institute of Mother and Child
    • Contact: Anna Fijałkowska, Professor; Phone Number: +48223277383; Email: anna.fijalkowska@imid.med.pl
    • Principal Investigator: Urszula Nowacka, MD, PhD
    • Sub-Investigator: Karolina Krajewska, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• women aged 18 years or older,
• singleton pregnancy,
• ≥32+0 and ≤36+6 weeks' of gestation,
• fluent in Polish or English,
• diagnosed with late-onset FGR based of the Delphi criteria,
• with positive EDF in UA,
• with macroscopically normal fetus on ultrasound assessment.

Exclusion Criteria:

• multiple pregnancy,
• fetal malformations,
• abnormal genetic testing results (if available),
• uncertain pregnancy dating,
• indication for immediate delivery within 48 hours after enrollment,
• preterm prelabour rupture of membranes.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: cCTG; cCTG group, that will undergo a following process: EFW and Doppler assessment biweekly, and instead of additional weekly Doppler-only assessment, the patients will be provided with an electronic cCTG device at no cost (Carebits). Women will be asked to apply Carebits device at least twice weekly for at least 30 minutes (e.g. Mondays-Thursdays) with minimum 72 hours interval in case of 2 sessions per week. The trace will be examined by an independent centre, available 24 hours daily. The person examining the trace is trained or already specialized in Obs&Gynae. In case of situation requiring medical intervention, the patient will be immediately contacted by phone and advised to self-refer to the nearest Antenatal Unit. In case of normal trace, a full report will follow within 30 minutes after last reading of the trace.	Device: cCTG; Self-applied home computerized CTG device used twice weekly instead of standard Doppler assessment once weekly.; Other Names: Carebits device; www.carebits.pl
Active Comparator: Doppler; Doppler group, that will undergo a standard process of antenatal care in case of FGR. The EFW and CTG STV will be assessed biweekly. In case of positive end-diastolic flow in UA, Doppler assessment (MCA PI, UA PI, DV PI, Ut PI) will be provided on a weekly basis. In case of deterioration to AEDF/REDF, further management will depend on clinical situation and the patient will be excluded from the study group (applies to both arms).	Diagnostic test: Doppler; Standard Doppler assessment provided once weekly in case of late FGR with positive end diastolic flow in the umbilical artery.; Other Names: Doppler assessment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Condition at birth	Incidence of Apgar score at 5 min <7 or arterial pH of <7.0 or venous <7.1 or resuscitation (compressions, medications, intubation)	5 minutes after delivery
Neonatal Intensive Care Unit admission	Incidence any admission to the Neonatal Intensive Care Unit	anytime after the recruitment visit or after delivery before discharge from the hospital or up to 6 weeks after delivery if discharged earlier
Brain injury	Incidence of Intraventricular haemorrhage (IVH) grade II or above-defined as bleeding into the ventricles; or hypoxic-ischaemic encephalopathy or periventricular leukomalacia or seizures recorded by EEG	anytime after the recruitment visit or after delivery before discharge from the hospital or up to 6 weeks after delivery if discharged earlier
Ventilation	defined as need of positive pressure (continuous positive airway pressure (CPAP or nasal CPAP) or intubation rate	anytime after the recruitment visit or after delivery before discharge from the hospital or up to 6 weeks after delivery if discharged earlier
Respiratory distress syndrome	defined as need of surfactant and ventilation as a result of prematurity	anytime after the recruitment visit or after delivery before discharge from the hospital or up to 6 weeks after delivery if discharged earlier
Cardiovascular support/treatment	Incidence of anaemia-defined as low haemoglobin and/or haematocrit requiring blood transfusion or DIC - disseminated coagulopathy or ductus arteriosus treatment or hypotensive treatment	anytime after the recruitment visit or after delivery before discharge from the hospital or up to 6 weeks after delivery if discharged earlier
Neonatal sepsis	Incidence of confirmed bacteraemia in cultures or necrotizing enterocolitis - Necrotising enterocolitis (NEC)	anytime after the recruitment visit or after delivery before discharge from the hospital or up to 6 weeks after delivery if discharged earlier
Retinopathy	incidence of retinopathy requiring laser or anti-VEGF administration	anytime after the recruitment visit or after delivery before discharge from the hospital or up to 6 weeks after delivery if discharged earlier
Fetal/neonatal death	Rate of death in utero or after delivery before discharge from the hospital or up to 4 weeks after delivery if discharged earlier	anytime after the recruitment visit or after delivery before discharge from the hospital or up to 4 weeks after delivery if discharged earlier

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maternal anxiety levels	measured by a screening Generalized Anxiety Disorder 7- question scale (GAD-7 scale). There are four possible answers to all the questions, corresponding to scores 0,1,2,3, respectively, therefore the total score ranges between 0 (not anxious) - 21 (severely anxious).	at the recruitment visit and every 2 weeks until delivery
Compliance	adherence to the plan of care - % of the patients attending scheduled visits	after the recruitment visit until delivery
Number of hospital visits	total number of meetings with the healthcare provider	after the recruitment visit until delivery
Mode of delivery	rate of vaginal/caesarean; spontaneous/planned/emergency	through study completion, an average of 5 weeks after the recruitment visit
Onset of labour	rate of spontaneous/induced/caesarean before uterine contractions	through study completion, an average of 5 weeks after the recruitment visit
Gestational hypertension	incidence of new onset hypertension (blood pressure ≥140/90 mmHg) after 20 weeks' of gestation in the absence of preeclampsia as defined by International Society for Study of Hypertension in Pregnancy (ISSHP)	between 20 weeks' gestation - up to 6 weeks after birth
Preeclampsia	incidence of preeclampsia defined by International Society for Study of Hypertension in Pregnancy (ISSHP) (maternal factors)	between 20 weeks' gestation - up to 6 weeks after birth

Collaborators and Investigators

• Sponsor: Institute of Mother and Child, Warsaw, Poland
• Collaborators: Bielanski Hospital
• Investigators: Principal Investigator: Urszula Nowacka, MD, Institute of Mother and Child, Warsaw, Poland

Publications and helpful links

General Publications

• Lees CC, Stampalija T, Baschat A, da Silva Costa F, Ferrazzi E, Figueras F, Hecher K, Kingdom J, Poon LC, Salomon LJ, Unterscheider J. ISUOG Practice Guidelines: diagnosis and management of small-for-gestational-age fetus and fetal growth restriction. Ultrasound Obstet Gynecol. 2020 Aug;56(2):298-312. doi: 10.1002/uog.22134. No abstract available.
• Nohuz E, Riviere O, Coste K, Vendittelli F. Prenatal identification of small-for-gestational age and risk of neonatal morbidity and stillbirth. Ultrasound Obstet Gynecol. 2020 May;55(5):621-628. doi: 10.1002/uog.20282. Epub 2020 Apr 6.
• Ciobanu A, Khan N, Syngelaki A, Akolekar R, Nicolaides KH. Routine ultrasound at 32 vs 36 weeks' gestation: prediction of small-for-gestational-age neonates. Ultrasound Obstet Gynecol. 2019 Jun;53(6):761-768. doi: 10.1002/uog.20258. Epub 2019 Apr 30.
• Figueras F, Gratacos E. Stage-based approach to the management of fetal growth restriction. Prenat Diagn. 2014 Jul;34(7):655-9. doi: 10.1002/pd.4412. Epub 2014 Jun 9.
• Gordijn SJ, Beune IM, Thilaganathan B, Papageorghiou A, Baschat AA, Baker PN, Silver RM, Wynia K, Ganzevoort W. Consensus definition of fetal growth restriction: a Delphi procedure. Ultrasound Obstet Gynecol. 2016 Sep;48(3):333-9. doi: 10.1002/uog.15884.
• Molina LCG, Odibo L, Zientara S, Obican SG, Rodriguez A, Stout M, Odibo AO. Validation of Delphi procedure consensus criteria for defining fetal growth restriction. Ultrasound Obstet Gynecol. 2020 Jul;56(1):61-66. doi: 10.1002/uog.20854. Epub 2020 Jun 7.
• Baschat AA. Planning management and delivery of the growth-restricted fetus. Best Pract Res Clin Obstet Gynaecol. 2018 May;49:53-65. doi: 10.1016/j.bpobgyn.2018.02.009. Epub 2018 Mar 1.
• Akolekar R, Ciobanu A, Zingler E, Syngelaki A, Nicolaides KH. Routine assessment of cerebroplacental ratio at 35-37 weeks' gestation in the prediction of adverse perinatal outcome. Am J Obstet Gynecol. 2019 Jul;221(1):65.e1-65.e18. doi: 10.1016/j.ajog.2019.03.002. Epub 2019 Mar 13.
• Antenatal and postnatal mental health: clinical management and service guidance. London: National Institute for Health and Care Excellence (NICE); 2018 Apr. Available from http://www.ncbi.nlm.nih.gov/books/NBK553127/
• Lai J, Syngelaki A, Nicolaides KH, von Dadelszen P, Magee LA. Impact of new definitions of preeclampsia at term on identification of adverse maternal and perinatal outcomes. Am J Obstet Gynecol. 2021 May;224(5):518.e1-518.e11. doi: 10.1016/j.ajog.2020.11.004. Epub 2020 Nov 6.

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2022
• Primary Completion (Anticipated): October 1, 2024
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: August 13, 2021
• First Submitted That Met QC Criteria: August 31, 2021
• First Posted (Actual): September 5, 2021

Study Record Updates

• Last Update Posted (Estimate): December 15, 2022
• Last Update Submitted That Met QC Criteria: December 13, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: ultrasound; pregnancy; Doppler; cardiotocography; fetal growth restriction; obstetrics; fetal growth retardation; intrauterine growth restriction; maternal-fetal medicine
• Additional Relevant MeSH Terms: Pathologic Processes; Fetal Diseases; Pregnancy Complications; Growth Disorders; Fetal Growth Retardation
• Other Study ID Numbers: InstituteMCPoland

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Data will be available on reasonable request
• IPD Sharing Time Frame: The deidentified participant data will become available upon publishing the protocol and results of the study. Study protocol will be available immediately following publication.
• IPD Sharing Access Criteria: The data will be provided on request for anyone after methodologically sound proposal (contact details: urszula.nowacka@imid.med.pl).
• IPD Sharing Supporting Information Type: Study Protocol; Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No