E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
First-trimester pre-eclampsia patients |
Pacientes con preeclampsia de primer trimestre |
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E.1.1.1 | Medical condition in easily understood language |
First-trimester pre-eclampsia patients |
Pacientes con preeclampsia de primer trimestre |
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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 | PT |
E.1.2 | Classification code | 10036485 |
E.1.2 | Term | Pre-eclampsia |
E.1.2 | System Organ Class | 10036585 - Pregnancy, puerperium and perinatal conditions |
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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 |
To demostrate no increasement of incidence of preterm pre-emclampsia, comparing with a control-group patients who are taking the treatment as usual, when sFlt-1/PlGF ratio is less than 38 and patients are under 24-27 weeks of pregnancy. |
Demostrar que en aquellas pacientes con ratio sFlt-1/PlGF <38 a las 24-27+6 SG, la suspensión del AAS no incrementa la incidencia de PE pretérmino respecto al grupo control, que mantendrá la toma de AAS. |
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E.2.2 | Secondary objectives of the trial |
- To demostrate that determination of sFlt-1/PlGF ratio, between 24-27+6 weeks of pregnancy, achieves to detect false positives using first-trimester pre-emclapsia screening. - To demostrate that patients within sFlt-1/PlGF ratio less than 38, between 24-27+6 weeks of prenancy, whether you suspend the treatment with ASA, it is not increase the maternal morbility or mortality. - To demostrate that patients within sFlt-1/PlGF ratio less than 38, between 24-27+6 weeks of prenancy, the suspension of ASA reduces the incidence of minor maternal hemorrhages. -To demostrate that in high-risk pre-eclampsia patients, the detection of sFlt-1/PlGF ratio less than 38 between 24-27+6 weeks of prenancy, assumes a relief for those patients who get stress as the cognisance of high-risk group assignment for patients - To know the outcome of all patients with high-risk pre-eclampsia. |
• Demostrar que la determinación del ratio sFlt-1/PlGF a las 24-27+6 SG consigue detectar los falsos positivos del cribado de PE de primer trimestre. • Demostrar que en aquellas pacientes con ratio sFlt-1/PlGF <38 a las 24-27+6 SG, la suspensión del AAS no incrementa la morbilidad ni la mortalidad materna. • Demostrar que en aquellas pacientes con ratio sFlt-1/PlGF <38 a las 24-27+6 SG, la suspensión del AAS reduce la incidencia de hemorragias maternas menores. • Demostrar que la obtención de un ratio sFlt-1/PlGF <38 a las 24-27+6 SG, en pacientes de alto riesgo de PE de primer trimestre supone un alivio del estrés materno por dejar de pertenecer a un grupo de alto riesgo. • Conocer el desenlace de todas las pacientes con alto riesgo de PE |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Patients older than 18 years old - Gestational period less than 28+0 weeks - Unique gestation - High-risk of pre-eclampsia for the first-trimester screening, defined through a validated multivariate algorithm for the population under study - AAS initiation taken ≤ 16 + 6 weeks of pregnancy - Ratio sFlt1 / PlGF determined between the weeks of pregnancy 24-27 + 6 - Voluntary signature of the informed consent |
• Pacientes mayores de 18 años. • Edad gestacional < 28+0 semanas • Gestación única • Alto riesgo de preeclampsia en el cribado de primer trimestre, definido a través de un algoritmo multivariante validado para la población objeto de estudio • Toma AAS iniciada ≤ 16 + 6 Semanas de gestación • Ratio sFlt1/PlGF determinado entre las semanas de gestación 24-27+6 • Firma voluntaria del consentimiento informado |
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E.4 | Principal exclusion criteria |
- Multiple gestation - Dead and/or multiple malformation fetus, including also any genetical and/or cromosomical disseas affected by the fetus. - Von Willebrand dissease. - ASA intolerance and /or allergy - Peptic ulcer - Patients with misunderstanding or not able to understand the protocol, including also any condition which could compromise the compliance of the protocol, according to the investigator's opinion. - AAS compliance <50% up to the current visit - Antiphospholipid syndrome - No signature of the informed consent |
• Gestación múltiple • Feto muerto o polimalformado o afecto de enfermedad genética o cromosómica conocida • Enfermedad de Von Willebrand • Alergia o intolerancia al AAS • Úlcera péptica • Pacientes incapaces de entender el protocolo del estudio o cualquier otra condición que en opinión del investigador pueda comprometer el cumplimiento del protocolo. • Cumplimiento AAS < 50% hasta la visita actual • Síndrome antifosfolípidos • No firmar el consentimiento informado |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Preterm preeclampsia rate (< 37 weeks) within the two arms of the high-risk group under sFlt1/PlGF ratio less than 38 between 24-27+6 weeks of pregnancy. |
- Tasa de preeclampsia pretérmino (< 37 semanas) en las dos ramas del grupo de alto riesgo y ratio sFlt1/PlGF < 38 en las semanas 24-27+6 de gestación. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
- At the end of the study period (24-27+6 - 37 weeks of pregnancy) |
- Al final del tiempo del ensayo (semanas 24-27+6 - 37 de gestación) |
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E.5.2 | Secondary end point(s) |
- Prevalence of early, preterm and late pre-eclampsia at high-risk group and ratio ≥ 38 - Rate of adherence to the treatment assignated to high-risk screening group of patients - Stress perception by 'Perceived Stress Scale (PSS) of Cohen, S., Kamarck, T., & Mermelstein, R. This scale is evaluated the last month, having 14 items with an outcome defined by an scale of 5 points. It will be done in both groups of study. Seeing questionaries at anexo section. - Hemorrhagea along gestation at both groups of study (studying symptoms such as epistaxis, gingivorrhagia and genital bleeding) - Rate of maternal issues in both groups (sFlt1/PlGF ratio < 38 and sFlt1/PlGF ratio≥ 38) such as placental detachment, caesarea detected by abnormal cardiotocography, fetus death, undertaking more than 2 antidepressants, eclampsia, diseminated intravascular coagulation, maternal mortality, postpartum hemorraghea, accurate lung oedema, brain vascular hemorraghea, stroke, sepsis, income to intensive care and second-surgery needed. - Neonatal complications in both groups such as early partum, income at intensive care, Acute respiratory distress, Grade II-IV intravascular hemorraghea, patent ductus arteriosus, renal disfuntion, Necrotizing enterocolitis, intestinal perforation, sepsis, retinopathy of prematurity, Bronchopulmonary dysplasia, Periventricular leukomalacia, intrauterine growth restriction, postnatal administration of sulphactants or inotropics drugs and/or death. |
• Prevalencia de PE precoz, pretérmino y tardía en el grupo con cribado de alto riesgo y ratio ≥ 38 • Tasa de cumplimiento del tratamiento asignado en las pacientes con cribado de alto riesgo. • Estudio del estrés percibido mediante el cuestionario Perceived Stress Scale (PSS) de Cohen, S., Kamarck, T., & Mermelstein, R. Esta escala evalúa el nivel de estrés percibido durante el último mes, consta de 14 ítems con un formato de respuesta de una escala de cinco puntos. Se pasará en ambos grupos. Ver cuestionario en la sección anexos. • Hemorragia durante la gestación en ambos grupos (epistaxis, gingivorragia y sangrado genital). • Tasa de complicaciones maternas en ambos grupos (< 38 y ≥ 38) (Desprendimiento de placenta, cesárea por cardiotocografía anormal, muerte fetal, necesidad de ≥2 fármacos antihipertensivos, eclampsia, coagulación intravascular diseminada, mortalidad materna, hemorragia postparto, edema agudo de pulmón, hemorragia vascular cerebral, embolia, sepsis, ingreso en la UCI y necesidad de segunda cirugía). • Complicaciones neonatales en ambos grupos (Parto prematuro, admisión UCI, distrés respiratorio, hemorragia intraventricular grado III-IV, conducto arterioso persistente, disfunción renal, enterocolitis necrotizante, perforación intestinal, sepsis, retinopatía del prematuro, displasia broncopulmonar, leucomalacia periventricular, retardo del crecimiento intrauterino, administración postnatal de surfactante o fármacos inotrópicos y / o la muerte) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Along the study period. - Along the study period. - 24-27+6, 28-31+6 weeks of pregnancy - 24-27+6, 28-31+6, 32-35+6, 36 y 37 weeks of pregnancy - 24-27+6, 28-31+6, 32-35+6, 36 y 37 weeks of pregnancy - 4 months after the birth of the baby |
- A lo largo del tiempo del estudio. - A lo largo del tiempo del estudio. - semanas 24-27+6, 28-31+6 de gestación. - semanas 24-27+6, 28-31+6, 32-35+6, 36 y 37 de gestación. - semanas 24-27+6, 28-31+6, 32-35+6, 36 y 37 de gestación. - 4 meses después del nacimiento del bebé |
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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 | No |
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) | 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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
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 |
pacientes con continuación del medicamento (AAS 150mg/24hrs hasta semana 36) |
Patients whom continue the treatment (ASA as a medical product) |
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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
| 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 | 9 |
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 | No |
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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4 months after the birth of the baby |
4 meses después del nacimiento del bebé |
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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 |