Pravastatin for Prevention of Preeclampsia
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 Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
|Official Title:||Pravastatin for the Prevention of Preeclampsia in High-Risk Women: A Phase I Pilot Study|
- Number and type of maternal adverse events [ Time Frame: From the date of randomization until the date of delivery, assessed up to 210 days ] [ Designated as safety issue: Yes ]
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)
- Number and type of fetal/neonatal adverse events [ Time Frame: From date of birth up to discharge or 120 days after birth. ] [ Designated as safety issue: Yes ]
The presence of adverse events will be assessed by evaluating
- Fetal and neonatal death
- Birthweight (including rate of small for gestational age)
- Apgar scores
- Ponderal index
- Congenital malformations
- Auditory brainstem response (ABR) evoked potential
- Cord blood lipid profile, AST/ALT, and CK levels
- Pharmacokinetic parameters of pravastatin sodium during pregnancy [ Time Frame: Between Pre-dose (0) and 24 hours post dose ] [ Designated as safety issue: Yes ]
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, 10hr, 12hr and 24hr post dose.
Time urine collection intervals: pre-dose (0) and 0-4hr, 4-8hr, 8-12hr, 12-24 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
|Study Start Date:||August 2012|
|Estimated Study Completion Date:||May 2015|
|Estimated Primary Completion Date:||January 2014 (Final data collection date for primary outcome measure)|
Active Comparator: Pravastatin Group
Pregnant women at high-risk for preeclampsia who are taking pravastatin during their pregnancy.
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 two cohorts. Each cohort will receive one of the following doses of pills: 10mg or 20mg.
Placebo Comparator: Control Group
Pregnant women who are at high-risk for developing preeclampsia who are taking a placebo during their pregnancy.
Women will be instructed to take a placebo pill daily beginning the day of randomization and ending the day of delivery.
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.
- 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).
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01717586
|Contact: Maged Costantine, MDfirstname.lastname@example.org|
|Contact: Linda Brown, MPH, DrPHemail@example.com|
|United States, Indiana|
|Indiana University School of Medicine||Recruiting|
|Indianapolis, Indiana, United States, 46202|
|Contact: Laura Haneline, MD 317-274-8916 firstname.lastname@example.org|
|Contact: David Flockhart, MD, PhD 317-630-8795 email@example.com|
|Principal Investigator: David Flockhart, MD, PhD|
|United States, Pennsylvania|
|University of Pittsburgh||Recruiting|
|Pittsburgh, Pennsylvania, United States, 15213|
|Contact: Steve Caritis, MD 412-641-4874 firstname.lastname@example.org|
|Contact: Raman Venkataramanan, PhD 412-648-8547 email@example.com|
|Principal Investigator: Steve Caritis, MD|
|United States, Texas|
|University of Texas Medical Branch||Recruiting|
|Galveston, Texas, United States, 77555|
|Contact: Maged Costantine, MD 409-772-1571 firstname.lastname@example.org|
|Contact: Gary D. Hankins, MD 409-772-1957 email@example.com|
|Principal Investigator: Gary D. Hankins, MD|
|United States, Washington|
|University of Washington||Recruiting|
|Seattle, Washington, United States, 98195|
|Contact: Mary F. Hebert, PharmD, FCCP 206-616-5016 firstname.lastname@example.org|
|Contact: Thomas Easterling, MD 206-543-1521 email@example.com|
|Principal Investigator: Mary F. Hebert, PharmD, FCCP|
|Principal Investigator:||Gary D. Hankins, MD||University of Texas|
|Principal Investigator:||Steve Caritis, MD||University of Pittsburgh|
|Principal Investigator:||Mary F. Hebert, PharmD, FCCP||University of Washington|
|Principal Investigator:||David Flockhart, MD, PhD||Indiana University|