Trial record 12 of 12 for:    Open Studies | "Pregnancy, High-Risk"

Pravastatin for Prevention of Preeclampsia

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Sponsor:
Collaborators:
University of Texas
University of Pittsburgh
University of Washington
Indiana University
RTI International
Information provided by (Responsible Party):
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:
NCT01717586
First received: January 3, 2012
Last updated: January 20, 2014
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Preeclampsia
Drug: Pravastatin
Drug: Placebo
Phase 1

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Primary Outcome Measures:
  • 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



Estimated Enrollment: 40
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)
Arms Assigned Interventions
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 two cohorts. Each cohort will receive one of the following doses of pills: 10mg or 20mg.
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Documented history (by chart review) of prior severe preeclampsia in either of the two pregnancies preceding the current one and requiring delivery at 34 weeks or less gestation.
  • 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

Exclusion Criteria:

  • Known chromosomal, genetic, or major fetal malformations, fetal demise, or planned termination
  • Multifetal gestation
  • Patient with contraindications for statin therapy

    • Hypersensitivity to pravastatin or any component of the product
    • Active liver disease in the past 6 months (acute hepatitis, chronic active hepatitis) by medical history
    • Unexplained elevations (1.5x normal) of serum transaminases persistent on repeated laboratory testin in the 6 months before this visit
  • Patients with any of the following conditions as it may predispose them to adverse events or side effects.

    • Current (past month) heavy alcohol use defined as ≥2 drinks per day
    • Illicit drug use
    • Amyotrophic lateral sclerosis (ALS)
    • Concomitant therapy with fibrates, niacin, cyclosporine, clarithromycin or erythromycin
    • Recent (<6 months) history of liver disease or have unexplained elevated transaminases or jaundice
    • History of cholestasis of the liver in prior pregnancy
    • Personal or family history of myopathy or rhabdomyolysis
  • Statin use in current pregnancy or in the last month prior to pregnancy
  • Patients with any of the following medical conditions as described in medical record or patient history:

    • Pregestational diabetes mellitus
    • HIV positive
    • Status post solid organ transplant
    • Chronic renal disease/insufficiency with baseline serum creatinine ≥1.5 mg/dL
    • Epilepsy or other seizure disorder
    • Uterine malformations
    • Cancer
    • Familial hypercholesterolemia
    • Heart disease including prior myocardial infarction and prior cerebrovascular accident
  • Concurrent and chronic ( > 6 months) use of medications with potential drug interactions with statins such as immunosuppressive drugs, gemfibrozil, niacin, erythromycin, itraconazole, cholestyramine, digoxin, rifampin (Patients will not be excluded if the drug has been discontinued)
  • Inability to tolerate oral medications secondary to severe nausea and vomiting of pregnancy
  • Participating in another intervention study that influences maternal and fetal morbidity and mortality
  • Plans to deliver in a non-network site.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01717586

Contacts
Contact: Maged Costantine, MD 409-772-1571 mmcostan@utmb.edu
Contact: Linda Brown, MPH, DrPH 301-816-4626 lindabrown@rti.org

Locations
United States, Indiana
Indiana University School of Medicine Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Laura Haneline, MD    317-274-8916    lhanelin@iupui.edu   
Contact: David Flockhart, MD, PhD    317-630-8795    dflockha@iupui.edu   
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    scaritis@mail.magee.edu   
Contact: Raman Venkataramanan, PhD    412-648-8547    rv@pitt.edu   
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    mmcostan@utmb.edu   
Contact: Gary D. Hankins, MD    409-772-1957    ghankins@utmb.edu   
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    mhebert@u.washington.edu   
Contact: Thomas Easterling, MD    206-543-1521    easter@u.washington.edu   
Principal Investigator: Mary F. Hebert, PharmD, FCCP         
Sponsors and Collaborators
University of Texas
University of Pittsburgh
University of Washington
Indiana University
RTI International
Investigators
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
  More Information

Additional Information:
No publications provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier: NCT01717586     History of Changes
Other Study ID Numbers: OPRU Pravastatin
Study First Received: January 3, 2012
Last Updated: January 20, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):
high-risk pregnancy
preeclampsia
pravastatin
Pravachol®
statin
safety
fetal morbidity and mortality
maternal morbidity and mortality
neonatal mortality
premature delivery
preemie

Additional relevant MeSH terms:
Pre-Eclampsia
Hypertension, Pregnancy-Induced
Pregnancy Complications
Pravastatin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 28, 2014