Pravastatin for Prevention of Preeclampsia (Statin)

The University of Texas System (UT)

Status and phase: Completed; Phase 1

Conditions: Preeclampsia

Treatments: Drug: Placebo; Drug: Pravastatin

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01717586

12-097 OPRU/OPRC Pravastatin

U54HD047891 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 48 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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48 participants in 2 patient groups, including a placebo group

Pravastatin Group

Active Comparator group

Description:

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

Treatment:

Drug: Pravastatin

Control Group

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo