Pravastatin for Prevention of Preeclampsia (Statin)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01717586|
Recruitment Status : Active, not recruiting
First Posted : October 30, 2012
Last Update Posted : December 15, 2021
|Condition or disease||Intervention/treatment||Phase|
|Preeclampsia||Drug: Pravastatin Drug: Placebo||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||48 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Pravastatin for the Prevention of Preeclampsia in High-Risk Women: A Phase I Pilot Study|
|Study Start Date :||August 2012|
|Estimated Primary Completion Date :||December 2022|
|Estimated Study Completion Date :||December 2022|
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 three cohorts. Each cohort will receive one of the following doses of pills: 10mg or 20mg or 40mg.
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.
- Number and type of maternal adverse events [ Time Frame: From the date of randomization until the date of delivery, assessed up to 210 days ]
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. ]
The presence of adverse events will be assessed by evaluating
- Fetal and neonatal death
- Birthweight (including rate of small for gestational age)
- Apgar scores
- 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 ]
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 post dose.
Time urine collection intervals: pre-dose (0) and 0-4hr, 4-8hr 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01717586
|United States, Illinois|
|Chicago, Illinois, United States, 60611|
|United States, Pennsylvania|
|University of Pittsburgh|
|Pittsburgh, Pennsylvania, United States, 15213|
|United States, Texas|
|University of Texas Medical Branch|
|Galveston, Texas, United States, 77555|
|Principal Investigator:||Maged Costantine, MD||UTexasGalveston; Ohio State|