MedPath

AtorvaStatin Postpartum and Reduction of Cardiovascular RisK

Phase 4
Not yet recruiting
Conditions
Hypertensive Disorders of Pregnancy
Preeclampsia
Gestational Hypertension
Interventions
Registration Number
NCT06632379
Lead Sponsor
Ohio State University
Brief Summary

The objective is to conduct a double-blinded randomized controlled trial of atorvastatin vs. placebo among postpartum individuals with hypertensive disorders of pregnancy, to improve cardiovascular risk score postpartum. For this, 76 individuals with hypertensive disorders of pregnancy (HDP) will be randomized to atorvastatin 10mg or placebo, which will be started in the postpartum period after cessation of breast feeding and continued for 3 months.

Detailed Description

Individuals will be followed for up to 1 year to address the following specific aims:

Specific Aim 1: To determine if among individuals diagnosed with hypertensive disorders of pregnancy (HDP), the use of atorvastatin 10 mg daily initiated in the postpartum period following cessation of breastfeeding and continued for 3 months, lowers cardiovascular risk, as measured by the Framingham Risk Score for Cardiovascular Disease (30 year risk, primary outcome) and cardiovascular risk prediction model (PREVENT, secondary outcome) compared with placebo; and if the benefit will persist for at least 3-6 months following discontinuation of atorvastatin treatment.

Specific Aim 2: To determine if among individuals diagnosed with HDP the use of atorvastatin 10 mg daily initiated in the postpartum period following cessation of breastfeeding and continued for 3 months lowers the frequency of metabolic syndrome, improves lipid levels, and reduces inflammatory markers compared with placebo; and if this benefit will persist for at least 3-6 months following discontinuation of atorvastatin treatment.

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
Female
Target Recruitment
76
Inclusion Criteria
  1. At least 24 hours after delivery
  2. ≥ 20 years old with the ability to give informed consent
  3. Diagnosis of gestational hypertension, preeclampsia prior to delivery admission, or diagnosed with preeclampsia during delivery admission, as determined by clinical team using the American College of Obstetricians and Gynecologists (ACOG) criteria.
  4. English speaking
Exclusion Criteria
  1. Individuals who were prescribed an 3-hydroxy-3 methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitor prior to or during pregnancy,
  2. Known familial hypercholesterolemia or pre-existing hyperlipidemia, specifically Low-density Lipoprotein (LDL) >190 prior to pregnancy or diagnosis of hyperlipidemia with prescription of HMG-CoA reductase inhibitor prior to delivery,
  3. Plan to breastfeed for >= 6 months,
  4. Plan for pregnancy conception in the next 6 months,
  5. Incarcerated individuals,
  6. Hypertensive diagnosis thought to be secondary to fetal condition,
  7. Contraindications to HMG-CoA reductase inhibitor therapy or known hypersensitivity to atorvastatin or any component,
  8. Active liver disease (acute hepatitis, chronic active hepatitis, unexplained persistent transaminitis (at least twice upper limit of normal serum transaminases)),
  9. History of rhabdomyolysis or myopathy,
  10. Human Immunodeficiency Virus (HIV) positivity, due to potential interactions between atorvastatin and HIV protease inhibitors,
  11. History of solid organ transplant, due to potential interactions between atorvastatin and immunosuppressants
  12. Active cancer, or
  13. Current use of medications with potential drug interactions, namely cyclosporine, clarithromycin, itraconazole, HIV protease inhibitors, rifampin, and digoxin.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
10 mg AtorvastatinAtorvastatin 10 mgAtorvastatin 10 mg daily for 3 months
PlaceboPlaceboIdentical appearing placebo for 3 months
Primary Outcome Measures
NameTimeMethod
The 30-year Framingham Risk Score for Cardiovascular DiseaseAfter 3 months of study treatment, up to 9 months after enrollment

Predicts 0-100% risk of "hard" CVD events (coronary death, myocardial infarction, stroke) based on sex, systolic blood pressure, antihypertensive treatment, total and high-density lipoprotein cholesterol, smoking, and diabetes mellitus. A higher number reflects a greater risk of adverse CVD events, whereas a lower number reflects lower risk.

Secondary Outcome Measures
NameTimeMethod
Apolipoprotein (b) levelFrom randomization until 6 months after stopping to use the study drug, up to 9 months
Drug Use and Side EffectsFrom randomization until 6 months after stopping to use the study drug, up to 9 months

Individuals will be contacted monthly via phone call to assess drug tolerability and use using a survey, which reviews any adverse events or concerns related to use of the study drug.

Framingham Risk Score for Cardiovascular Disease 3-6 months following medication cessationAnytime after 3-6 months of stopping to use the study drug, up to 9 months from randomization

Enrolled individuals will be contacted via telephone at 3-6 months after they complete medication use and will be invited to a visit for a Framingham Risk Score calculation. The Framingham Risk Score predicts 0-100% risk of CVD events, with a higher number reflecting a greater risk of adverse CVD events, whereas a lower number reflects lower risk.

PREVENT (AHA Predicting Risk of CVD Events) scoreFrom randomization until 6 months after stopping to use the study drug, up to 9 months

A glomerular filtration rate will be calculated for each enrolled individual upon enrollment and at the additional biospecimen visits in order to enable calculation of the PREVENT score.

Rates of primary care provider (PCP) visits within 9-12 months of deliveryFrom randomization until 6 months after stopping to use the study drug, up to 12 months from delivery

Enrolled individuals will undergo a telephone survey at 9-12 months postpartum, assessing whether they have attended a visit with a primary care provider (internal medicine, family medicine or primary care nurse practitioner), and for what reason, since the time of their delivery

Waist circumferenceFrom randomization until 6 months after stopping to use the study drug, up to 9 months

Waist circumference in centimeters will be measured at the study visits to help identify those with metabolic syndrome (circumference of 88 cm or more).

Fasting glucoseFrom randomization until 6 months after stopping to use the study drug, up to 9 months

Fasting glucose levels will be measured at the study visits to help identify those with metabolic syndrome (fasting glucose above or equal to 100 mg/dL).

Number of individuals diagnosed with metabolic syndromeFrom randomization until 6 months after stopping to use the study drug, up to 9 months

The presence of metabolic syndrome will be defined as 3 or more of the following, which are also listed as individual outcomes: waist circumference greater or equal to 88 cm, triglycerides greater or equal to 150 mg/dL, HDL cholesterol \<50 mg/dL, blood pressure greater or equal to 130/85, and fasting glucose greater or equal to 100 mg/dL.

Lipid levelsFrom randomization until 6 months after stopping to use the study drug, up to 9 months

Serum testing for total cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides

Hypertension diagnosis & need for antihypertensive therapyFrom randomization until 6 months after stopping to use the study drug, up to 9 months

Blood pressure will be measured at the study visits to identify new development of hypertension; enrolled individuals will be asked if they have started medication for hypertension

Diabetes diagnosis & need for anti-glycemic therapyFrom randomization until 6 months after stopping to use the study drug, up to 9 months

Hemoglobin A1C will be measured at the study visits to identify new development of diabetes mellitus (HbA1C \> 6.5%) and individuals will be asked if they have started anti-glycemic medication

Systolic blood pressureFrom randomization until 6 months after stopping to use the study drug, up to 9 months
Estimated glomerular filtration rateFrom randomization until 6 months after stopping to use the study drug, up to 9 months
High-sensitivity C-reactive protein (Hs-CRP) levelFrom randomization until 6 months after stopping to use the study drug, up to 9 months
Lipoprotein (a) levelFrom randomization until 6 months after stopping to use the study drug, up to 9 months

Trial Locations

Locations (1)

The Ohio State University Wexner Medical Center OB/GYN Maternal and Fetal Medicine

🇺🇸

Columbus, Ohio, United States

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