Pre-eclampsia Pregnancy and Childbirth
Conditions
Interventions
Current interventions as of 01/07/2020:
This is a double-blind randomised placebo-controlled trial for which the eligible participants will be identified by a screening study. In the participating cen
Sponsors
Fundación para la Formación e Investigación Sanitarias de la Región de Murcia
King's College Hospital
Eligibility
Sex/Gender
Female
Inclusion criteria
Inclusion criteria: Current participant inclusion criteria as of 01/07/2020: 1. Pregnant women without established preeclampsia 2. Singleton pregnancy 3. Live fetus at 35+0-36+6 weeks’ gestation 4. Informed and written consent 5. Age =18 years 6. Not unconscious or very ill 7. No serious mental illness 8. No learning difficulties 9. Fluent in local language or translation by interpreter Inclusion criteria for participant selection for RCT: 1. Same as for screening 2. Identified at screening as being at high-risk for term-PE by the algorithm combining maternal history and characteristics, MAP, PLGF and sFLT-1 3. Informed and written consent 4. No planned delivery within 7 days of planned randomisation date; 5. No major fetal abnormality; 6. No statin use within 28 days prior to randomisation; 7. None of the following contraindications for statin therapy: 7.1. Hypersensitivity to pravastatin or any component of the product 7.2. Lactose intolerance 7.3. Current or previous cancer 7.4. Previous solid organ transplant 7.5. Active liver disease (acute hepatitis, chronic active hepatitis) in the past 6 months 7.6. Chronic renal disease/insufficiency with baseline serum creatinine =1.5mg/dL 7.7. History of myopathy or rhabdomyolysis 7.8. ALT and/or AST levels = 2 x the upper limit of normal 7.9. Creatine kinase levels = 5 x the upper limit of normal 7.10. Concurrent and chronic (>6 months) use of medications with potential drug interactions with statins, such as immunosuppressive drugs, fibrates, gemfibrozil, therapeutic doses of niacin for hyperlipidaemia (low doses found in dietary/nutritional supplements such as pregnancy supplements may be used), 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) 7.11. Participating in another intervention study that influences the outcomes of this study Previous participant inclusion criteria: 1. Pregnant women without established preeclampsia 2. Singleton pregnancy 3. Live fetus at 35+0-36+6 weeks’ gestation 4. Informed and written consent 5. Age >18 years 6. Not unconscious or very ill 7. No serious mental illness 8. No learning difficulties 9. Fluent in local language or translation by interpreter 10. No major fetal abnormality 11. No statin use within 28 days prior to randomisation 12. None of the following contraindications for statin therapy: 12.1. Hypersensitivity to pravastatin or any component of the product 12.2. Lactose intolerance 12.3. Current or previous cancer 12.4. Previous solid organ transplant 12.5. Active liver disease (acute hepatitis, chronic active hepatitis) in the past 6 months 12.6. Chronic renal disease/insufficiency with baseline serum creatinine >1.5mg/dL 12.7. History of myopathy or rhabdomyolysis 12.8. ALT and/or AST levels = 2 x the upper limit of normal 12.9. Creatine kinase levels = 5 x the upper limit of normal 12.10. 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) 12.11. Participating i
Exclusion criteria
Exclusion criteria: Current participant exclusion criteria as of 01/07/2020: For the randomised trial, same as for screening, but in addition: 1. Major fetal abnormality 2. Women with established PE 3. Statin use within 28 days prior to randomisation 4. Women with contraindications for statin therapy: 4.1. Hypersensitivity to pravastatin or any component of the product 4.2. Lactose intolerance 4.3. Current or previous cancer 4.4. Previous solid organ transplant 4.5. Active liver disease (acute hepatitis, chronic active hepatitis) in the past 6 months 4.6. Chronic renal disease/insufficiency with baseline serum creatinine = 1.5mg/dL 4.7. History of myopathy or rhabdomyolysis 4.8. ALT and/or AST levels > = 2 x the upper limit of normal 4.9. Creatine kinase levels > = 5 x the upper limit of normal 4.10. Concurrent and chronic (>6 months) use of medications with potential drug interactions with statins, such as immunosuppressive drugs, fibrates, gemfibrozil, therapeutic doses of niacin for hyperlipidaemia (low doses found in dietary/nutritional supplements such as pregnancy supplements may be used), 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) 5. Participating in another intervention study that influences the outcomes of this study Previous participant exclusion criteria: For the randomised trial, same as for screening, but in addition: 1. Major fetal abnormality 2. Women with established PE 3. Statin use within 28 days prior to randomisation 4. Women with contraindications for statin therapy: 4.1. Hypersensitivity to pravastatin or any component of the product 4.2. Lactose intolerance 4.3. Current or previous cancer 4.4. Previous solid organ transplant 4.5. Active liver disease (acute hepatitis, chronic active hepatitis) in the past 6 months 4.6. Chronic renal disease/insufficiency with baseline serum creatinine > 1.5mg/dL 4.7. History of myopathy or rhabdomyolysis 4.8. ALT and/or AST levels > = 2 x the upper limit of normal 4.9. Creatine kinase levels > = 5 x the upper limit of normal 4.10. 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) 5. Participating in another intervention study that influences the outcomes of this study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of PE with delivery, assessed by examination of patient hospital records and patient interviews | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 01/07/2020: Assessed by examination of patient hospital records and patient interviews: 1. Adverse outcome of pregnancy at any gestation 2. Adverse outcome of pregnancy at =37 weeks’ gestation 3. Stillbirth or neonatal death 4. Neonatal morbidity 5. Neonatal therapy 6. Incidence of low birth weight 7. sFLT-1 and PLGF value at 1 and 3 weeks after the onset of treatment 8. Pravastatin safety assessment during pregnancy: at 1 and 2 weeks after the onset of treatment, at term, 6 weeks after delivery Previous secondary outcome measures: Assessed by examination of patient hospital records and patient interviews: 1. Adverse outcome of pregnancy at any gestation 2. Adverse outcome of pregnancy at >37 weeks’ gestation 3. Stillbirth or neonatal death 4. Neonatal morbidity 5. Neonatal therapy 6. Incidence of low birth weight 7. sFLT-1 and PLGF value at 1 and 3 weeks after the onset of treatment 8. Pravastatin safety assessment during pregnancy: at 1 and 2 weeks after the onset of treatment, at term, 6 weeks after delivery | — |
Countries
Belgium, England, Spain, United Kingdom
Outcome results
None listed