Pravastatin to Prevent Preeclampsia

NCT03944512 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: HD036801-Pravastatin5U10HD036801-20
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 12

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.

Conditions

Preeclampsia; Obstetric Labor Complications; Hypertension in Pregnancy

Keywords

Pregnancy; Preeclampsia

Outcome Measures

Primary Outcomes (1)

• Proportion of Participants With Composite of Preeclampsia, Fetal Loss and Maternal Death

  Proportion of participants demonstrating a composite of preeclampsia, fetal loss, or maternal death. 1. Baseline Normotensive: a) Severe hypertension (HTN) or b) Mild HTN w/ any of the following: i.) New-onset proteinuria or doubling in protein w/ baseline proteinuria ii.) Thrombocytopenia iii.) Progressive renal insufficiency iv). Impaired liver function v.) Pulmonary edema vi.) New-onset \& persistent cerebral or visual symptoms 2. Baseline chronic HTN: any of the following a)Severe HTN b) New onset proteinuria or doubling in protein from baseline proteinuria c)Thrombocytopenia d) Progressive renal insufficiency e) Impaired liver function f) Pulmonary edema g) New-onset \& persistent cerebral or visual symptoms. 3. HELLP a) Hemolysis AND b)Thrombocytopenia AND c) AST/ALT ≥ 70 IU/L 4. Atypical HELLP an occurrence of 2 of the 3: a) Hemolysis, b)Thrombocytopenia, OR c) AST/ALT ≥ 70 IU/L 5. Eclampsia 6. Competing outcomes: maternal death before delivery or fetal loss \< 20wks, 0 days

  48 hours postpartum

Secondary Outcomes (41)

• Proportion of Participants With Preeclampsia With Severe Features

  48 hours postpartum

• Proportion of Participants With Gestational Hypertension

  48 hours postpartum

• Proportion of Participants With Pregnancy Associated Hypertension

  48 hours postpartum

• Proportion of Participants With Postpartum Preeclampsia

  48 hours postpartum through 6 weeks post partum

• Proportion of Participants With Gestational Diabetes

  At any time during pregnancy through delivery (up to approximately 30 weeks)

Study Arms (2)

Pravastatin

EXPERIMENTAL

20 mg pravastatin daily

Drug: Pravastatin

Placebo

PLACEBO COMPARATOR

Identical appearing daily placebo

Other: Placebo

Interventions

Pravastatin DRUG

20 mg Pravastatin taken daily

Pravastatin

Placebo OTHER

Identical appearing placebo pill

Placebo

Eligibility Criteria

• Age: 16 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• years or older at time of consent with ability to give informed consent
• 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.
• Gestational age at randomization between 12 weeks 0 days and 16 weeks 6 days based on clinical information and evaluation of the earliest ultrasound.
• 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.
• Normal serum transaminase (AST/ALT) concentrations documented in the last 6 months.

You may not qualify if:

• Monoamniotic gestation because of the risk of fetal demise
• Known chromosomal, genetic or major malformations
• Contraindications for statin therapy:
• Hypersensitivity to pravastatin or any component of the product
• Active liver disease: acute hepatitis or chronic active hepatitis
• Statin use in current pregnancy
• Patients with any of the following medical conditions:
• Uncontrolled hypothyroidism with a TSH level above 10 mIU/L, because of increased risk of myopathy
• HIV positive, because of increased risk of myopathy with use of protease inhibitors
• Chronic renal disease with baseline serum creatinine ≥1.5 mg/dL, because of association with adverse pregnancy outcomes
• 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.
• Participating in another intervention study that influences the primary outcome in this study
• Plan to deliver in a non-network site
• 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.

Sponsors & Collaborators

• The George Washington University Biostatistics Center: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (12)

University of Alabama - Birmingham

Birmingham, Alabama, 35233, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Columbia University

New York, New York, 10032, United States

Location

University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Case Western Reserve-Metro Health

Cleveland, Ohio, 44109, United States

Location

Ohio State University Hospital

Columbus, Ohio, 43210, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Magee Women's Hospital of UPMC

Pittsburgh, Pennsylvania, 15213, United States

Location

Brown University

Providence, Rhode Island, 02905, United States

Location

University of Texas Medical Branch

Galveston, Texas, 77555, United States

Location

University of Texas - Houston

Houston, Texas, 77030, United States

Location

University of Utah Medical Center

Salt Lake City, Utah, 84132, United States

Location

Related Publications (1)

• 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.

  PMID: 26723196 BACKGROUND

MeSH Terms

Conditions

Pre-Eclampsia; Obstetric Labor Complications; Hypertension, Pregnancy-Induced

Interventions

Pravastatin

Condition Hierarchy (Ancestors)

Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Results Point of Contact

• Title: Maged M. Costantine, MD
• Organization: The Ohio State University

maged.costantine@osumc.edu

614-293-9036

Study Officials

• Maged Costantine, MD

  Ohio State University

  PRINCIPAL INVESTIGATOR

• Monica Longo, MD, PHD

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

  STUDY DIRECTOR

• Rebecca Clifton, PhD

  The George Washington University Biostatistics Center

  PRINCIPAL INVESTIGATOR

• Victoria Pemberton, RNC, MS, CCRC

  National Heart, Lung, and Blood Institute (NHLBI)

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: 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.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: May 7, 2019
• First Posted: May 9, 2019
• Study Start: July 17, 2019
• Primary Completion: June 6, 2021
• Study Completion: June 20, 2024
• Last Updated: December 23, 2025
• Results First Posted: December 23, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

US (12)