E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Raised blood pressure in pregnancy as a result of abnormal function of the placenta
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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 examine if the use of Pravastatin starting at 35-36 weeks' gestation in women at increased risk of developing pre-eclampsia (high blood pressure in pregnancy) reduces the incidence and severity of this complication. |
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E.2.2 | Secondary objectives of the trial |
To examine if the use of Pravastatin reduces the incidence of delivery due to complications from high blood pressure, fetal growth restriction, stillbirth or neonatal complications, rate of neonatal intensive care unit admission, and the incidence of placental abruption (separation). A safety assessment of pravastatin administration during pregnancy will also be undertaken.
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
For the screening study: • Singleton pregnancy; • Live fetus at 35+0-36+6 weeks’ gestation; • Informed and written consent.
For the randomised trial: • Same as for screening • High-risk for term-PE at screening by the algorithm combining maternal history and characteristics, MAP, PLGF and sFLT-1; • Informed and written consent.
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E.4 | Principal exclusion criteria |
For the screening study: • Age <18 years; • Multiple pregnancy; • Unconscious or very ill; • Serious mental illness; • Learning difficulties; • Not fluent in local language and absence of interpreter.
For the randomised trial: • Same as for screening, but in addition: • Major fetal abnormality; • Women with established PE; • Statin use within 28 days prior to randomisation; • Women with contraindications for statin therapy: -Hypersensitivity to pravastatin or any component of the product; -Lactose intolerance -Current or previous cancer -Previous solid organ transplant -Active liver disease (acute hepatitis, chronic active hepatitis) in the past 6 months -Chronic renal disease/insufficiency with baseline serum creatinine >1.5mg/dL -History of myopathy or rhabdomyolysis; -ALT and/or AST levels ≥ 2 x the upper limit of normal -Creatine kinase levels ≥ 5 x the upper limit of normal -Concurrent and chronic (>6 months) use of medications with potential drug interactions with statins, such as immunosuppressive drugs, fibrates, gemfibrozil, niacin, protease inhibitors, efavirenz (non-nucleoside reverse transcriptase inhibitor), erythromycin, clarithromycin, itraconazole, cholestyramine, digoxin, rifampicin (patients will not be excluded if the drug has been discontinued, or is prescribed for a short duration of time); • Participating in another intervention study that influences the outcomes of this study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Incidence of PE after randomisation |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Once delivered, data on pregnancy outcome, including labour onset, gestational age at delivery, mode of delivery, development of hypertension in pregnancy, neonatal birth weight and gender, and other obstetrics complications, will be collected from the hospital maternity records or their general medical practitioners. In addition, the obstetric records of women with pre-existing or pregnancy associated hypertension will be examined to determine if the condition is pre-eclampsia requiring delivery after randomisation. |
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E.5.2 | Secondary end point(s) |
• To determine the effect of pravastatin on adverse outcome of pregnancy at any gestation. o PE, with delivery at any gestation o GH, with delivery at any gestation o SGA (<5th percentile), with delivery at any gestation o Stillbirth at any gestation o Placental abruption (clinically or on placental examination) at any gestation o Composite of any of the above • To determine the effect of pravastatin on adverse outcome of pregnancy at >37 weeks’ gestation. o PE, with delivery at >37 weeks o GH, with delivery at >37 weeks o SGA (<5th percentile), with delivery at >37 weeks o Stillbirth at >37 weeks o Placental abruption (clinically or on placental examination) at >37 weeks o Composite of any of the above • To determine the effect of pravastatin on stillbirth or neonatal death o Neonatal death o Neonatal morbidity o To determine the effect of pravastatin on neonatal morbidity Intraventricular haemorrhage,neonatal sepsis, neonatal anaemia, respiratory distress syndrome, necrotising enterocolitis o Composite of any of the above • To determine the effect of pravastatin on neonatal therapy o Neonatal intensive care unit admission o Ventilation - Defined as need of positive pressure (continuous positive airway pressure (CPAP) or nasal continuous positive airway pressure (NCPAP)) or intubation o Composite of any of the above • To determine the effect of pravastatin on the incidence of low birthweight below the 3rd, 5th and 10th centile. o Birthweight will be recorded in the participants’ medical notes and birthweight percentile for gestational age at delivery is calculated using a normal range derived from our population. • To determine the effect of pravastatin on sFLT-1 and PLGF value 1 and 3 weeks after the onset of treatment • Pravastatin safety assessment during pregnancy |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Once delivered, data on pregnancy outcome, including labour onset, gestational age at delivery, mode of delivery, development of hypertension in pregnancy, neonatal birth weight and gender, and other obstetrics complications, will be collected from the hospital maternity records or their general medical practitioners. Neonatal outcomes will be collected from Special Care Baby Unit. |
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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 | Yes |
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 | 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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
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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The end of the study for individual participants will be defined as 6 weeks after the birth of the baby/end of the pregnancy.
The end of the study as a whole will be defined as the last visit of the last patient (n=1,120) with details of their complete pregnancy outcome. This will take approximately 15 months to complete.
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |