Pravastatin to Prevent Preeclampsia

Purpose

This study is a double-blind randomized placebo-controlled trial of 1,550 high-risk women to assess whether daily treatment with pravastatin administered early in pregnancy reduces the rate of a composite outcome of preeclampsia, fetal loss and maternal death. Women with a prior history of preeclampsia with preterm delivery less than 34 weeks will be randomized to pravastatin or placebo daily until delivery. Women will have monthly study visits during pregnancy, a follow-up visit at 6 weeks postpartum and children will have follow-up visits at 2 and 5 years of age.

Conditions

  • Preeclampsia
  • Obstetric Labor Complications
  • Hypertension in Pregnancy

Eligibility

Eligible Ages
Over 16 Years
Eligible Genders
Female
Accepts Healthy Volunteers
No

Inclusion Criteria

  1. 16 years or older at time of consent with ability to give informed consent
  2. Single or twin gestation with cardiac activity in one or both fetuses. Higher order multifetal gestations reduced to twins, either spontaneously or therapeutically, are not eligible unless the reduction occurred by 13 weeks 6 days project gestational age.
  3. Gestational age at randomization between 12 weeks 0 days and 16 weeks 6 days based on clinical information and evaluation of the earliest ultrasound.
  4. Documented history (by chart or delivery/operative note review) of prior preeclampsia with delivery less than or equal to 34 weeks 0 days gestation in any previous pregnancy. If in the index pregnancy, the woman was induced by 34 weeks 0 days gestation and delivered within 48 hours in the same hospitalization, that woman would be eligible.
  5. Normal serum transaminase (AST/ALT) concentrations documented in the last 6 months.

Exclusion Criteria

  1. Monoamniotic gestation because of the risk of fetal demise
  2. Known chromosomal, genetic or major malformations
  3. Fetal demise or planned termination of pregnancy. Selective reduction by 13 weeks 6 days gestation, from triplets to twins or twins to singleton is not an exclusion.
  4. Contraindications for statin therapy:
  5. Hypersensitivity to pravastatin or any component of the product
  6. Active liver disease: acute hepatitis or chronic active hepatitis
  7. Statin use in current pregnancy
  8. Patients with any of the following medical conditions:
  9. Uncontrolled hypothyroidism with a TSH level above 10 mIU/L, because of increased risk of myopathy
  10. HIV positive, because of increased risk of myopathy with use of protease inhibitors
  11. Chronic renal disease with baseline serum creatinine ≥1.5 mg/dL, because of association with adverse pregnancy outcomes
  12. Current use of concomitant medication with potential for drug interaction with statins (i.e.,, cyclosporine, fibrates, niacin, erythromycin). Patients will not be excluded if the drug is discontinued (at least one week) prior to randomization.
  13. Participating in another intervention study that influences the primary outcome in this study
  14. Plan to deliver in a non-network site
  15. Participation in this trial in a previous pregnancy. Patients who were screened in a previous pregnancy, but not randomized, do not have to be excluded.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
The study is a randomized controlled multi-center clinical trial of 1,550 women with a prior history of preeclampsia that required delivery at less than or equal to 34 weeks 0 days gestation, randomized to one of two arms at participating Maternal Fetal Medicine Units Network clinical centers. 20 mg pravastatin daily Identical appearing daily placebo
Primary Purpose
Prevention
Masking
Double (Participant, Investigator)
Masking Description
Consenting women will be assigned to pravastatin or placebo in a 1:1 ratio according to a randomization sequence prepared and maintained centrally by the Data Coordinating Center (DCC). The two study medication arms of the study (pravastatin or placebo) are double masked; neither the patient nor the clinical staff will be aware of the treatment assignment.

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Pravastatin
20 mg pravastatin daily
  • Drug: Pravastatin
    20 mg Pravastatin taken daily
Placebo Comparator
Placebo
Identical appearing daily placebo
  • Other: Placebo
    Identical appearing placebo pill

Recruiting Locations

University of Texas Medical Branch
Galveston, Texas 77555
Contact:
Ashley Salazar, MSN
409-772-0312
assalaza@utmb.edu

More Details

NCT ID
NCT03944512
Status
Recruiting
Sponsor
The George Washington University Biostatistics Center

Study Contact

Rebecca Clifton, PhD
301-881-9260
rclifton@bsc.gwu.edu

Detailed Description

Preeclampsia complicates approximately 3% to 5% of pregnancies and remains a major cause of maternal and neonatal morbidities and mortality. Women who experience preeclampsia in one pregnancy are at higher risk of developing preeclampsia in a subsequent pregnancy than those who have never experienced the condition. There is evidence from laboratory studies and clinical trials, as well as biological plausibility, to suggest that statins may prevent the development of preeclampsia by reversing various pathways associated with preeclampsia. Pravastatin has a favorable safety profile and pharmacokinetic properties.

The study is a randomized placebo-controlled multi-center clinical trial of 1,550 women with a prior history of preeclampsia that required delivery at less than 34 weeks, randomized to either 20mg pravastatin or an identical appearing placebo daily until delivery. Women with a singleton or twin gestation will be randomized between 12 weeks 0 days and 16 weeks 6 days will be followed monthly during pregnancy and then at 6 weeks postpartum. Children will have follow-up visits at 2 and 5 years of age to assess growth, cognition, behavior, motor skills, vision and hearing.