Randomised controlled trial with pravastatin versus placebo for prevention of preeclampsia

• Register: ISRCTN
• Last refreshed on: 5 July 2021
• Main ID: ISRCTN16123934
• Date of registration: 16/04/2018
• Prospective Registration: Yes
• Primary sponsor: Fundación para la Formación e Investigación Sanitarias de la Región de Murcia
• Public title: Randomised controlled trial with pravastatin versus placebo for prevention of preeclampsia
• Scientific title: Randomised controlled trial with pravastatin versus placebo for prevention of preeclampsia
• Date of first enrolment: 16/08/2018
• Target sample size: 1120
• Recruitment status: Completed
• URL: http://isrctn.com/ISRCTN16123934
• Study type: Interventional
• Study design: Randomised; Both; Design type: Prevention, Drug, Cohort study (Prevention)
• Phase: Not Applicable

Countries of recruitment

Belgium, Spain, United Kingdom

Contacts

• Name: Kypros Nicolaides

Key inclusion & exclusion 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 ac
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


Age minimum:
Age maximum:
Gender: Female

Health Condition(s) or Problem(s) studied

Pre-eclampsia
Pregnancy and Childbirth

Intervention(s)

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 centres in Spain, Belgium and the UK, all women attending for their routine hospital visit in pregnancy at 35+0-36+6 weeks’ gestation will be screened to identify a high-risk group for development of Preeclampsia (PE). In this visit the trialists will record maternal characteristics and medical history, measure the maternal MAP and serum PLGF and sFLT-1 and on the basis of these results estimate the risk for term-PE. Women that are screened positive for term-PE will be invited to participate in the randomised trial of pravastatin. Participants will take one capsule per day of either pravastatin 20mg or matching placebo. Participants will be asked to stop taking capsules at 41 weeks’ gestation or in the event of early delivery, at the onset of labour (maximum duration of 42 days). The women will have a follow-up visit 6 weeks after delivery.

Previous interventions:
This is a double-blind randomised placebo-controlled trial for which the eligible participants will be identified by a screening study. In the participating centres in Spain, Italy, Belgium, Romania and the UK, all women attending for their routine hospital visit in pregnancy at 35+0-36+6 weeks’ gestation will be screened to identify a high-risk group for development of PE. In this visit the trialists will record maternal characteristics and medical history, measure the maternal MAP and serum PLGF and sFLT-1 and on the basis of these results estimate the risk for term-PE. Women that are screened positive for term-PE will be invited to participate in th

Primary Outcome(s)

Incidence of PE with delivery, assessed by examination of patient hospital records and patient interviews

Secondary Outcome(s)

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

Secondary ID(s)

2016-005206-19

33496

Source(s) of Monetary Support

Fetal Medicine Foundation

Secondary Sponsor(s)

King's College Hospital

Ethics review

Status:
Approval date:
Contact:

London - London Bridge Research Ethics Committee, 20/02/2017, ref: 17/LO/0130

Results

• Results available: Yes
• Date Completed: 30/11/2020