E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Fetal growth restriction |
foetale groeivertraging |
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E.1.1.1 | Medical condition in easily understood language |
Fetal growth restriction |
foetale groeivertraging |
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E.1.1.2 | Therapeutic area | Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
We aim to evaluate the effectiveness of sildenafil (versus placebo) in achieving healthy perinatal survival, in women with singleton pregnancies with severe fetal growth restriction of placental origin. |
We willen de effectiviteit onderzoeken van sildenafil om gezonde perinatale overleving te bereiken bij vrouwen met een eenlingzwangerschap met ernstige foetale groeivertraging met placentaire oorzaak. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of study are 1) to evaluate whether Sildenafil citrate, compared to placebo, increases the likelihood of improved fetal growth velocity assessed by ultrasound abdominal circumference measurements (AC); 2) to evaluate whether Sildenafil citrate, compared to placebo, increases the likelihood of age-adequate performance on the two-year Bayley scales of infant development (BSID)-III (composite cognitive score and composite motor score); 3) to assess co-incidence and severity of the maternal syndrome of pre-eclampsia / HELLP-syndrome |
De secundaire doelstellingen van de studie zijn te onderzoeken of Sildenafil citraat tov placebo 1) de foetale groeisnelheid doet toenemen, beoordeeld door echoscopische buikomtrek metingen 2) de ontwikkeling op 2 jaar doet verbeteren, beoordeeld door Bailey testen. 3) de incidentie van maternale hypertensieve syndromen verbetert |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria ((I OR II) AND III): I. at 200-276 weeks: an ultrasound measurement of the fetal abdominal circumference (AC) <3rd percentile for gestational age or an ultrasound estimate of fetal weight (EFW) <5th percentile OR II. at 280-296 weeks: an ultrasound estimate of fetal weight (EFW) <700 grams AND III. likely placental origin defined by (a AND/OR b AND/OR c AND/OR d) a. the presence of uterine artery notching b. abnormal flow velocity patterns of the umbilical artery or middle cerebral artery c. maternal hypertensive disorders d. low PlGF in point-of-care assessment |
Inclusion criteria ((I OR II) AND III): I. at 200-276 weeks: an ultrasound measurement of the fetal abdominal circumference (AC) <3rd percentile for gestational age or an ultrasound estimate of fetal weight (EFW) <5th percentile OR II. at 280-296 weeks: an ultrasound estimate of fetal weight (EFW) <700 grams AND III. likely placental origin defined by (a AND/OR b AND/OR c AND/OR d) a. the presence of uterine artery notching b. abnormal flow velocity patterns of the umbilical artery or middle cerebral artery c. maternal hypertensive disorders d. low PlGF in point-of-care assessment |
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E.4 | Principal exclusion criteria |
Exclusion criteria: I. Plan to terminate pregnancy for maternal or fetal indication within days II. Known multiple pregnancy III. identified congenital anomalies or congenital infection IV. Maternal age at eligibility <18 years |
Exclusion criteria: I. Plan to terminate pregnancy for maternal or fetal indication within days II. Known multiple pregnancy III. identified congenital anomalies or congenital infection IV. Maternal age at eligibility <18 years |
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E.5 End points |
E.5.1 | Primary end point(s) |
The Dutch STRIDER (Sildenafil TheRapy In Dismal prognosis Early-onset fetal growth Restriction) Trial is a double-blind randomised controlled trial (RCT) designed to evaluate whether in pregnant women with severe early-onset FGR of placental origin, Sildenafil citrate compared with placebo increases the likelihood of intact perinatal survival until term age. This is defined by the survival to term age without evidence of either severe central nervous system (CNS) injury (by ultrasound and/or magnetic resonance imaging [MRI]) or non-CNS severe morbidity (bronchopulmonary dysplasia, retinopathy of prematurity, or necrotising enterocolitis requiring surgery).
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The Dutch STRIDER (Sildenafil TheRapy In Dismal prognosis Early-onset fetal growth Restriction) Trial is a double-blind randomised controlled trial (RCT) designed to evaluate whether in pregnant women with severe early-onset FGR of placental origin, Sildenafil citrate compared with placebo increases the likelihood of intact perinatal survival until term age. This is defined by the survival to term age without evidence of either severe central nervous system (CNS) injury (by ultrasound and/or magnetic resonance imaging [MRI]) or non-CNS severe morbidity (bronchopulmonary dysplasia, retinopathy of prematurity, or necrotising enterocolitis requiring surgery).
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Term age |
Uitgerekende datum |
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E.5.2 | Secondary end point(s) |
The secondary objectives of study are 1) to evaluate whether Sildenafil citrate, compared to placebo, increases the likelihood of improved fetal growth velocity assessed by ultrasound abdominal circumference measurements (AC); 2) to evaluate whether Sildenafil citrate, compared to placebo, increases the likelihood of age-adequate performance on the two-year Bayley scales of infant development (BSID)-III (composite cognitive score and composite motor score); 3) to assess co-incidence and severity of the maternal syndrome of pre-eclampsia / HELLP-syndrome
Announced subgroup analyses: to evaluate the effect of Sildenafil on the abovementioned outcome measures, in subgroups defined by a) an abnormal or normal serum level of placental growth factor (PlGF); b) absent/reversed umbilical arterial end diastolic flow (REDF) at commencement of treatment; c) other patient characteristics available at baseline such as gestational age, estimated fetal weight; |
The secondary objectives of study are 1) to evaluate whether Sildenafil citrate, compared to placebo, increases the likelihood of improved fetal growth velocity assessed by ultrasound abdominal circumference measurements (AC); 2) to evaluate whether Sildenafil citrate, compared to placebo, increases the likelihood of age-adequate performance on the two-year Bayley scales of infant development (BSID)-III (composite cognitive score and composite motor score); 3) to assess co-incidence and severity of the maternal syndrome of pre-eclampsia / HELLP-syndrome
Announced subgroup analyses: to evaluate the effect of Sildenafil on the abovementioned outcome measures, in subgroups defined by a) an abnormal or normal serum level of placental growth factor (PlGF); b) absent/reversed umbilical arterial end diastolic flow (REDF) at commencement of treatment; c) other patient characteristics available at baseline such as gestational age, estimated fetal weight; |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Term age and 2 years |
Uitgerekende datum en 2 jaar |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |