Pravastatin for Prevention of Preeclampsia (Statin)

March 20, 2023 updated by: The University of Texas Medical Branch, Galveston

Pravastatin for the Prevention of Preeclampsia in High-Risk Women: A Phase I Pilot Study

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Preeclampsia shares pathogenic similarities with adult cardiovascular diseases as well as many risk factors. Endothelial dysfunction and inflammation are fundamental for the initiation and progression of both. There is strong evidence that 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) are beneficial in primary and secondary prevention of cardiovascular mortality and other cardiovascular events. Biological plausibility as well as animal data supports a similar role for statins in preeclampsia.

Currently, there are no clinically available agents to prevent preeclampsia. However because of the below properties of statins, this class of medications could substantially contribute to preeclampsia prevention.

  1. Statins pleiotropic actions on various mechanisms: reversing the angiogenic imbalance by upregulating vascular endothelial growth factor (VEGF) and placental growth factor (PlGF), and reducing the antiangiogenic factors such as soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng).
  2. Statins up regulation of endothelial nitric oxide synthase, leading to improved nitric oxide production in the vasculature and to activate the heme oxygenase-1/carbon monoxide (HO-1/CO) pathway, protecting the endothelium and reducing the inflammatory and oxidative insults.

The purpose of this pilot study is to evaluate the maternal-fetal safety and pharmacokinetic (PK) profiles of pravastatin when used in pregnant women at high-risk of developing preeclampsia.

Study Type

Interventional

Enrollment (Actual)

48

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • University of Pittsburgh
    • Texas
      • Galveston, Texas, United States, 77555
        • University of Texas Medical Branch

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

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.

  • 18 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

Exclusion Criteria:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Pravastatin Group
Pregnant women at high-risk for preeclampsia who are taking pravastatin during their pregnancy.
Drug: Pravastatin
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.
Other Names:
  • pravastatin sodium
  • Brand name: Pravachol®
Placebo Comparator: Control Group
Pregnant women who are at high-risk for developing preeclampsia who are taking a placebo during their pregnancy.
Drug: Placebo
Women will be instructed to take a placebo pill daily beginning the day of randomization and ending the day of delivery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number and type of maternal adverse events
Time Frame: From the date of randomization until the date of delivery, assessed up to 210 days

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

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
Time Frame: Between Pre-dose (0) and 24 hours post dose

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The University of Texas Medical Branch, Galveston

Collaborators

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

Investigators

  • Principal Investigator: Maged Costantine, MD, UTexasGalveston; Ohio State

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2012

Primary Completion (Anticipated)

December 1, 2025

Study Completion (Anticipated)

December 1, 2025

Study Registration Dates

First Submitted

January 3, 2012

First Submitted That Met QC Criteria

October 26, 2012

First Posted (Estimate)

October 30, 2012

Study Record Updates

Last Update Posted (Actual)

March 22, 2023

Last Update Submitted That Met QC Criteria

March 20, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 12-097 OPRU/OPRC Pravastatin
  • U54HD047891 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

per NICHD guidelines

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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