Pravastatin to Prevent Preeclampsia

NCT ID: NCT03944512

Last Updated: 2025-12-23

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 102 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-17
• Study Completion Date: 2024-06-20

Brief Summary

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.

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.

Conditions

Preeclampsia; Obstetric Labor Complications; Hypertension in Pregnancy

Keywords

Pregnancy; Preeclampsia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Pravastatin

20 mg pravastatin daily

Group Type: EXPERIMENTAL

Pravastatin

Intervention Type: DRUG

20 mg Pravastatin taken daily

Placebo

Identical appearing daily placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Identical appearing placebo pill

Interventions

Pravastatin

20 mg Pravastatin taken daily

Intervention Type: DRUG

Placebo

Identical appearing placebo pill

Intervention Type: OTHER

Eligibility Criteria

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:

1. Hypersensitivity to pravastatin or any component of the product

2. Active liver disease: acute hepatitis or chronic active hepatitis

5. Statin use in current pregnancy

6. Patients with any of the following medical conditions:

1. Uncontrolled hypothyroidism with a TSH level above 10 mIU/L, because of increased risk of myopathy

2. HIV positive, because of increased risk of myopathy with use of protease inhibitors

3. Chronic renal disease with baseline serum creatinine ≥1.5 mg/dL, because of association with adverse pregnancy outcomes

7. 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.

8. Participating in another intervention study that influences the primary outcome in this study

9. Plan to deliver in a non-network site

10. 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.

• Minimum Eligible Age: 16 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

The George Washington University Biostatistics Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Maged Costantine, MD

Role: PRINCIPAL_INVESTIGATOR

Ohio State University

Monica Longo, MD, PHD

Role: STUDY_DIRECTOR

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Rebecca Clifton, PhD

Role: PRINCIPAL_INVESTIGATOR

The George Washington University Biostatistics Center

Victoria Pemberton, RNC, MS, CCRC

Role: STUDY_DIRECTOR

National Heart, Lung, and Blood Institute (NHLBI)

Locations

University of Alabama - Birmingham

Birmingham, Alabama, United States

Northwestern University

Chicago, Illinois, United States

Columbia University

New York, New York, United States

University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, United States

Case Western Reserve-Metro Health

Cleveland, Ohio, United States

Ohio State University Hospital

Columbus, Ohio, United States

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Magee Women's Hospital of UPMC

Pittsburgh, Pennsylvania, United States

Brown University

Providence, Rhode Island, United States

University of Texas Medical Branch

Galveston, Texas, United States

University of Texas - Houston

Houston, Texas, United States

University of Utah Medical Center

Salt Lake City, Utah, United States

Countries

United States

References

Costantine MM, Cleary K, Hebert MF, Ahmed MS, Brown LM, Ren Z, Easterling TR, Haas DM, Haneline LS, Caritis SN, Venkataramanan R, West H, D'Alton M, Hankins G; Eunice Kennedy Shriver National Institute of Child Health and Human Development Obstetric-Fetal Pharmacology Research Units Network. Safety and pharmacokinetics of pravastatin used for the prevention of preeclampsia in high-risk pregnant women: a pilot randomized controlled trial. Am J Obstet Gynecol. 2016 Jun;214(6):720.e1-720.e17. doi: 10.1016/j.ajog.2015.12.038. Epub 2015 Dec 23.

Reference Type: BACKGROUND

PMID: 26723196 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

5U10HD036801-20

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HD036801-Pravastatin

Identifier Type: -

Identifier Source: org_study_id