Pravastatin for Prevention of Preeclampsia



Status:Recruiting
Conditions:Women's Studies
Therapuetic Areas:Reproductive
Healthy:No
Age Range:18 - Any
Updated:2/23/2019
Start Date:August 2012
End Date:December 2021
Contact:Maged Costantine, MD
Email:mmcostan@utmb.edu
Phone:409-772-1571

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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.

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.

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
We found this trial at
3
sites
4200 Fifth Ave
Pittsburgh, Pennsylvania 15260
(412) 624-4141
Principal Investigator: Steve Caritis, MD
Phone: 412-641-4874
University of Pittsburgh The University of Pittsburgh is a state-related research university, founded as the...
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301 University Blvd
Galveston, Texas 77555
(409) 772-1011
Principal Investigator: Gary D. Hankins, MD
Phone: 409-772-1571
University of Texas Medical Branch Established in 1891 as the University of Texas Medical Department,...
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303 East Superior Street
Chicago, Illinois 60611
Phone: 312-926-2323
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Chicago, IL
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