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

Study Overview
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Brief Summary
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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.

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

Conditions
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Fetal Growth Restriction

Intervention / Treatment
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* Device: cCTG
* Diagnostic Test: Doppler


Participation Criteria
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Eligibility Criteria
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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.

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: Supportive Care
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: cCTG<br>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<br>* Self-applied home computerized CTG device used twice weekly instead of standard Doppler assessment once weekly.<br>* Other names: www.carebits.pl;|
| Active Comparator: Doppler<br>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<br>* Standard Doppler assessment provided once weekly in case of late FGR with positive end diastolic flow in the umbilical artery.<br>* Other names: Doppler assessment;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ultrasound, fetal growth restriction, fetal growth retardation, pregnancy, cardiotocography, Doppler, intrauterine growth restriction, maternal-fetal medicine, obstetrics