Pravastatin for Prevention of Preeclampsia

NCT01717586 | Completed Phase 1 DMC

• 2 other identifiers: 12-097 OPRU/OPRC PravastatinU54HD047891
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 3

Brief Summary

The primary purpose of this pilot study is to determine the pharmacokinetic (PK) parameters and collect preliminary safety data for pravastatin when used as a prophylactic daily treatment in pregnant women at high risk of preeclampsia.

Conditions

Preeclampsia

Keywords

preeclampsia; pravastatin; Pravachol®; statin; high-risk pregnancy; safety; fetal morbidity and mortality; maternal morbidity and mortality; neonatal mortality; premature delivery; preemie

Outcome Measures

Primary Outcomes (3)

• Number and type of maternal adverse events

  The presence of side effects and adverse events will be assessed at each study visit by: * a symptoms checklist * any other report of adverse events * at select visits: laboratory testing for liver function test(LFT) and creatine kinase(CK)

  From the date of randomization until the date of delivery, assessed up to 210 days

• Number and type of fetal/neonatal adverse events

  The presence of adverse events will be assessed by evaluating * Fetal and neonatal death * Birthweight (including rate of small for gestational age) * Apgar scores * Congenital malformations * Auditory brainstem response (ABR) evoked potential * Cord blood lipid profile, AST/ALT, and CK levels

  From date of birth up to discharge or 120 days after birth.

• Pharmacokinetic parameters of pravastatin sodium during pregnancy

  Timed blood and urine collection performed once between 18 wks 0 days GA and 23 wks 6 days GA and once between 30 wks 0 days GA and 33 wks 6 days GA. Timed blood collection intervals: pre-dose(0)and 0.5hr, 1hr, 1.5hr, 2hr, 3hr, 4hr, 6hr, 8hr post dose. Time urine collection intervals: pre-dose (0) and 0-4hr, 4-8hr hr post dose. Evaluation parameters:Maximum observed plasma concentration (Cmax) and peak time (Tmax), Steady-state area under the plasma concentration-time curve during the 24-h dosing interval (AUC0-24h), Steady-state apparent oral clearance (CL/F), Elimination half-life (t½), Renal clearance of pravastatin

  Between Pre-dose (0) and 24 hours post dose

Study Arms (2)

Pravastatin Group

ACTIVE COMPARATOR

Pregnant women at high-risk for preeclampsia who are taking pravastatin during their pregnancy.

Drug: Pravastatin

Control Group

PLACEBO COMPARATOR

Pregnant women who are at high-risk for developing preeclampsia who are taking a placebo during their pregnancy.

Drug: Placebo

Interventions

Pravastatin DRUG

Comparison of different drug dosages. Women will be instructed to take a pravastatin pill everyday starting the day of randomization and ending the day of delivery. The women will be divided into three cohorts. Each cohort will receive one of the following doses of pills: 10mg or 20mg or 40mg.

Also known as: pravastatin sodium, Brand name: Pravachol®

Pravastatin Group

Placebo DRUG

Women will be instructed to take a placebo pill daily beginning the day of randomization and ending the day of delivery.

Control Group

Eligibility Criteria

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

You may qualify if:

• Documented history (review of chart or delivery note) of prior severe early onset PE in a prior pregnancy and requiring delivery ≤340/7 weeks' gestation. If in the index pregnancy, the woman was induced at the upper limit of 34 0/7 weeks of pregnancy and delivered within 48 hours in the same hospitalization, that woman could be enrolled. Women with severe PE in a pregnancy remote (greater than 2 pregnancies removed) from the current pregnancy do not qualify.
• years or older with the ability to give informed consent
• Singleton pregnancy
• Normal serum transaminase (ALT and AST) concentrations in the last 6-months
• Gestational age (GA) between 12 weeks 0 days to 16 weeks 6 days based on clinical information and confirmed by an ultrasound per study procedures.
• Willingness to participate in planned PK study visits

You may not qualify if:

• Known chromosomal, genetic, or major fetal malformations, fetal demise, or planned termination
• Patients with contraindications for statin therapy:
• Hypersensitivity to pravastatin or any component of the product
• Active liver disease (acute hepatitis, chronic active hepatitis, persistently abnormal liver enzymes (2 x normal of serum transaminases)
• History of myopathy or rhabdomyolysis
• Patients with any of the following conditions:
• HIV positive
• Status post solid organ transplant
• Chronic renal disease/insufficiency with baseline serum creatinine ≥1.5 mg/dL
• Uterine malformations (didelphus, bicornuate, unicornate)
• Cancer
• Statin use in current pregnancy
• Current use of medications with potential drug interactions with statins, such as cyclosporine, fibrates, gemfibrozil, niacin, erythromycin, fluconazole, itraconazole, cholestyramine, digoxin, rifampin (patients will not be excluded if the drug has been discontinued, or is prescribed for a short duration of time)
• Participating in another intervention study that influences the outcomes of this study
• Plans to deliver in a non-network site

Sponsors & Collaborators

• The University of Texas Medical Branch, Galveston: lead
• University of Pittsburgh: collaborator
• Northwestern University: collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (3)

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Texas Medical Branch

Galveston, Texas, 77555, United States

Location

Related Publications (4)

• 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

• Costantine MM, West H, Wisner KL, Caritis S, Clark S, Venkataramanan R, Stika CS, Rytting E, Wang X, Ahmed MS; Eunice Kennedy Shriver National Institute of Child Health and Human Development Obstetric-Fetal Pharmacology Research Centers (OPRC) Network, Bethesda, MD. A randomized pilot clinical trial of pravastatin versus placebo in pregnant patients at high risk of preeclampsia. Am J Obstet Gynecol. 2021 Dec;225(6):666.e1-666.e15. doi: 10.1016/j.ajog.2021.05.018. Epub 2021 May 24.

  PMID: 34033812 BACKGROUND

• Costantine MM, Cleary K; Eunice Kennedy Shriver National Institute of Child Health and Human Development Obstetric--Fetal Pharmacology Research Units Network*. Pravastatin for the prevention of preeclampsia in high-risk pregnant women. Obstet Gynecol. 2013 Feb;121(2 Pt 1):349-353. doi: 10.1097/AOG.0b013e31827d8ad5.

  PMID: 23344286 BACKGROUND

• Costantine MM, Clifton RG, Boekhoudt TM, Lawrence K, Gyamfi-Bannerman C, Wisner KL, Grobman W, Caritis SN, Simhan HN, Hebert MF, Longo M, Saade GR; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network and the Obstetric-Fetal Pharmacology Research Centers Network. Long-term neurodevelopmental follow-up of children exposed to pravastatin in utero. Am J Obstet Gynecol. 2023 Aug;229(2):153.e1-153.e12. doi: 10.1016/j.ajog.2023.02.016. Epub 2023 Feb 24.

  PMID: 36842489 DERIVED

MeSH Terms

Conditions

Pre-Eclampsia; Premature Birth

Interventions

Pravastatin

Condition Hierarchy (Ancestors)

Hypertension, Pregnancy-Induced; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Obstetric Labor, Premature; Obstetric Labor Complications

Intervention Hierarchy (Ancestors)

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

Study Officials

• Maged Costantine, MD

  UTexasGalveston; Ohio State

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 3, 2012
• First Posted: October 30, 2012
• Study Start: August 1, 2012
• Primary Completion: February 12, 2024
• Study Completion: February 12, 2024
• Last Updated: May 4, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)