E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Early fetal growth restriction |
Restrição de crescimento fetal precoce |
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E.1.1.1 | Medical condition in easily understood language |
Fetal growth restriction |
Restrição de crescimento fetal precoce |
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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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10070532 |
E.1.2 | Term | Fetal growth restriction |
E.1.2 | System Organ Class | 100000004868 |
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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 |
Our global aim is to assess if LMWH improves the outcomes of early-restricted fetuses (ERF). |
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E.2.2 | Secondary objectives of the trial |
1) To determine if enoxaparin increases the mean neonatal birth weight and decreases neonatal intensive care admissions 2) To determine if enoxaparin improves maternal and fetal Doppler parameters in this group of patients 3) To determine if enoxaparin is associated with alterations in placental pathology 4) To determine if enoxaparin is associated with alterations in Sflt1-PLGF ratio 5) To determine if there is a change in number or composition of STD-EV between healthy and FGR pregnancies 6) To determine if enoxaparin is associated with alterations in STD-EV in FGR pregnancies |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Sub-study B - Molecular study: healthy participants (40 women)
Objectives: 1) To determine if there is a change in number or composition of STD-EV between healthy and FGR pregnancies 2) To determine if enoxaparin is associated with alterations in STD-EV in FGR pregnancies
This sub-study aims to recruit healthy, pregnant women in order to obtain blood samples to compare with the ones collected in the clinical trial described above. These women will not take part in the main clinical trial. Forty healthy women will be approached for consent after their first trimester ultrasound at Maternidade Dr. Alfredo da Costa (the first forty eligible women that accept to participate after the beginning of recruitment). After obtaining written consent and checking for eligibility, all participants will be given a study ID. Their pregnancies will be monitored according to national guidelines for monitoring of low-risk pregnancies. In addition, blood will be collected at 24, 28, 32, 36 and 40 weeks of gestation; and 48 hours post-partum. |
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E.3 | Principal inclusion criteria |
Eligible women referred to our FGR unit who consent to participate in the study. Eligible women are considered those who fulfill all the following eligibility criteria: a) being over 18 years old; b) being able to provide consent; c) having a viable singleton pregnancy with diagnosed early FGR confirmed in our unit according to the 2016 consensus criteria |
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E.4 | Principal exclusion criteria |
diagnosed fetal chromosomal abnormalities; c) associated fetal morphological malformations; d) evidence of fetal infection (serological or after invasive testing); e) use of aspirin, LMWH or NFH in the index pregnancy before randomization; f) maternal history of allergy to LMWH or non-fractionated heparin (NFH); g) hypersensitivity to pork products; h) maternal history of heparin-induced thrombocytopenia; i) maternal thrombocytopenia (platelets < 100 000); k) history of maternal anticoagulant hemostatic disorder; j) presence of placental hematoma; k) maternal diabetic retinopathy; l) bacterial endocarditis; m) high risk of bleeding (recent ophthalmological, spinal or brain surgery); n) previous hemorrhagic stroke; o) persistent blood pressure > 160/100 mmHg, despite optimal anti-hypertensive regimen; p) active ulcerative or angiodysplastic diseases; q) history of severe renal disease (eGFR <30mL/min). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary: Gestational age at delivery |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary: Evolution of fetal doppler parameters (umbilical artery pulsatility index, middle cerebral artery pulsatility index, cerebral-placental ratio, ductus venosus pulsatility index); evolution of maternal doppler parameters (uterine artery pulsatility index); maternal weight gain during pregnancy; newborn weight, percentile, umbilical artery pH and Apgar score in the 5th minute; neonatal intensive care admission and duration of admission; a composite outcome of severe neonatal morbidity (evidence of one or more of: intraventricular hemorrhage grade 3 or 4; cystic periventricular leukomalacia; chronic lung disease; retinopathy of prematurity requiring treatment; necrotizing enterocolitis requiring surgery); gestational hypertension or preeclampsia; placental abruption; antepartum hemorrhage; maternal thrombocytopenia (platelets < 100 000 x 109/L); stillbirth; preterm birth; mode of delivery; indication for delivery; postpartum hemorrhage; placental pathology; sFLT1-PLGF ratio; STD-EV (number and composition)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
During all pregnancy and after delivery |
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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 | Yes |
E.6.5 | Efficacy | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Yes |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Standard of care (ultrasound surveillance) |
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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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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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Date of hospital discharge after delivery (for the mothers and babies) |
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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 | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |