Trial record 2 of 12 for:
nichd High-Risk Pregnancy
Pravastatin for Prevention of Preeclampsia
This study is currently recruiting participants.
Verified December 2012 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 14, 2013
Last verified: December 2012
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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:
|
|
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.
- 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.
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 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
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 14, 2013 |
| 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:
|
Hypertension, Pregnancy-Induced Pregnancy Complications Pre-Eclampsia 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 May 22, 2013