Randomised trial of pravastatin versus placebo for the prevention of high blood pressure in pregnancy

• Register: ISRCTN
• Last refreshed on: 8 April 2019
• Main ID: ISRCTN17787139
• Date of registration: 18/11/2015
• Prospective Registration: Yes
• Primary sponsor: Health Foundation for Education and Research in the Region of Murcia (Fundación para la Formación e Investigación Sanitaria)
• Public title: Randomised trial of pravastatin versus placebo for the prevention of high blood pressure in pregnancy
• Scientific title: RandomiSed conTrolled trial with prAvasTatin versus placebo for preventIoN of preeclampsia
• Date of first enrolment: 07/03/2016
• Target sample size: 1684
• Recruitment status: Completed
• URL: http://isrctn.com/ISRCTN17787139
• Study type: Interventional
• Study design: Multicentre double-blind randomised controlled trial (Prevention)
• Phase: Phase III

Countries of recruitment

Spain, United Kingdom

Contacts

• Name: Liona Poon

Key inclusion & exclusion criteria

Inclusion criteria:
1. Age > 18 years
2. Singleton pregnancies
3. Live fetus at 11-13 weeks' of gestation
4. High-risk for preterm-PE at 11-13 weeks by the algorithm combining maternal history and characteristics, biophysical findings (mean arterial pressure and uterine artery Dopplers) and biochemical factors (placental growth factor)
5. English or Spanish speaking (otherwise interpreters will be used)
6. Informed and written consent

Exclusion criteria:
1. Statin use in current pregnancy (administration must have ceased >28 days prior to randomisation)
2. Pregnancies complicated by major fetal abnormality identified at the 11-13 weeks assessment
3. Women who are unconscious or severely ill, those with learning difficulties, or serious mental illness
4. Women with contraindications for statin therapy
5. Hypersensitivity to Pravastatin or any component of the product
6. Active liver disease in the past 6 months (acute hepatitis, chronic active hepatitis) by medical history
7. Unexplained elevations (1.5x normal) of serum transaminases (ALT and AST), confirmed either by available blood results within the recruiting hospital in the last 6 months or blood taken prior to randomisation or jaundice
8. Women with any of the following conditions as it may predispose them to adverse events or side effects
9. Current (last 28 days) heavy alcohol use defined as =2 drinks per day
10. Illicit drug use
11. Amyotrophic lateral sclerosis (ALS)
12. Concomitant therapy with amiodarone, azole antifungals, diltiazem, gemfibrozil, nefazodone, nicotinic acid, protease inhibitors, efavirenz (non-nucleoside reverse transcriptase inhibitior), verapamil, fibrates, niacin (vitamin B3), cyclosporin, clarithromycin or erythromycin or other macrolide antibiotics
13. History of cholestasis of the liver in prior pregnancy
14. Personal or family history of myopathy or rhabdomyolysis
15. Women with any of the following medical conditions as described in medical record or patient history
16. Pregestational diabetes mellitus
17. Status post solid organ transplant
18. Chronic renal disease/insufficiency with baseline serum creatinine =1.5 mg/dL
19. Epilepsy or other seizure disorder
20. Uterine malformations
21. Cancer
22. Heart disease including prior myocardial infarction and prior cerebrovascular accident.
23. Concurrent and chronic (>6 months) use of medications with potential drug interactions with statins such as immunosuppressive drugs, gemfibrozil, niacin, erythromycin, itraconazole, cholestyramine, digoxin, rifampicin (Patients will not be excluded if the drug has been discontinued)
24. Inability to tolerate oral medications secondary to severe nausea and vomiting of pregnancy
25. Participating in another intervention study that influences maternal and fetal morbidity and mortality
26. Plans to deliver in a non-network site
27. Any other reason the clinical investigators think will prevent the potential participant from complying with the trial protocol


Age minimum:
Age maximum:
Gender: Female

Health Condition(s) or Problem(s) studied

Pre-eclampsia
Pregnancy and Childbirth

Intervention(s)

All women attending for the routine risk assessment for Down's syndrome at 11-13 weeks will be screened for pre-eclampsia. Women will then be classified as high­ and low risk for pre­-eclampsia based on the combination of maternal history, biophysical findings (mean arterial blood pressure and uterine artery Dopplers) and biochemical factor (PlGF). Patients found to be at high risk of developing pre-­eclampsia will receive information regarding the implications of this finding and will be offered the option of participating in a randomised study of pravastatin vs. placebo. Informed and written consent will be sought from those agreeing to participate in the study.

Study participants have an equal chance of being allocated into one of the two groups - pravastatin 20mg or placebo. The investigators, participants, and clinicians will not be aware of the treatment assignments. The participants will take one tablet daily from randomisation (11-14 weeks) until 36 weeks’ gestation or earlier in the event of preterm delivery.

Follow­-up clinical visits for all participants will be carried out at 19-24 weeks, 30-34 weeks and at 36 weeks. At these visits, a routine fetal scan, measurements of uterine artery Doppler, blood pressure, maternal blood levels of PlGF will be carried out. Trial participants will be telephoned at 16 weeks and 28 weeks to address concerns and enquire about side effects and compliance with medication. They will also be followed up by a further telephone interview 30 days after the last dose of medication.

Data on pregnancy and neonatal outcomes will be collected from the hospital maternity records or their general practitioners. In the event that the neonates are admitted to Special Care Baby Unit (SCBU)/Neonatal Intensive Care Unit (NICU), additional neonatal outcomes will be collected from the discharge summary of SCBU/NICU.

Primary Outcome(s)

Incidence of preterm pre-­eclampsia (PE) < 37 weeks

Secondary Outcome(s)

1. Incidence of early-PE (<34 weeks) and total PE (at any gestation)
2. Neonatal birthweight below the 3rd, 5th and 10th centile
3. Stillbirth or neonatal death due to any cause
4. Stillbirth or neonatal death ascribed to PE or fetal growth restriction
5. Stillbirth or neonatal death in association with maternal or neonatal bleeding
6. Rate of neonatal intensive care unit admission
7. Composite measure of neonatal mortality and morbidity
8. Placental abruption (clinically or on placental examination)
9. Spontaneous preterm delivery <34 weeks and <37 weeks

Secondary ID(s)

FFIS/2015/01/ST

Source(s) of Monetary Support

Fetal Medicine Foundation

Ethics review

Status:
Approval date:
Contact:

Not provided at time of registration.

Results

• Results available: Yes
• Date Completed: 06/03/2018