Response to Anti-hypertensives in Pregnant and Postpartum Patients

Study Overview
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Brief Summary
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In this study, the investigators will evaluate the blood pressure response to nifedipine and labetalol in pregnant and postpartum patients, who present with hypertensive disease in pregnancy with severe range blood pressure defined as greater than 160/110. These anti-hypertensives are first line therapy for management of severe range blood pressures in pregnancy and postpartum by the American Congress of Obstetricians and Gynecologist (ACOG). In addition at the Mount Sinai West site, the investigators will also analyze the ADRB1 and similar genes involved in beta blockade, genes involved in calcium channel blockade and other genes implicated in blood pressure response among pregnant and postpartum patients receiving labetalol and nifedipine. This analysis will be used to determine if a pharmacogenetic association exists between variant alleles in these receptors in the pregnant and postpartum population.

Detailed Description
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Hypertensive disease in pregnancy is a major cause of maternal morbidity and mortality. This condition is responsible for about 12% of the maternal deaths in the United States. Currently, if pregnant patients present with severe hypertension they are either given IV labetalol, IV hydralazine of nifedipine based on individual provider preference. There are few studies in the literature comparing oral nifedipine and IV labetalol with mixed data showing either they are equally effective or a faster time to achieving target blood pressure for patients who received nifedipine. In this study, the investigators will evaluate if there is a difference in time to achieve goal blood pressure in pregnant and postpartum patients who are treated with nifedipine and labetalol for severe range blood pressures defined as greater than 160/110. These anti-hypertensives are first line therapy for management of severe range blood pressures in pregnancy and postpartum by the American Congress of Obstetricians and Gynecologist (ACOG).

Official Title
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Ethnic Differences in Anti-Hypertensive Medication Response Among Pregnant and Postpartum Patients

Conditions
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Hypertension in Pregnancy, Preeclampsia

Intervention / Treatment
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* Drug: Nifedipine
* Drug: Labetalol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: pregnant patients from 20 weeks to up to 6 weeks postpartum between the ages of 18-55. persistent severe range blood pressures (2 readings or more within 15 minutes) of either 160mmHg systolic or 110mmHg diastolic. Exclusion Criteria: multiple gestation patients with non-reassuring fetal heart rate (category 3) patients with abruptio placenta patients with renal impairment history of heart failure history of cardiac arrhythmia use of anti-hypertensive medications in the past 24 hours patients with allergies or medical contraindications to labetalol or nifedipine.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients who present to the hospitals in this study will be randomized to receive IV labetalol or oral nifedipine when presenting with persistent severe range blood pressures (2 readings or more within 15 minutes) of either 160mmHg systolic or 110mmHg diastolic. These anti-hypertensives are first line therapy for management of severe range blood pressures by the American Congress of Obstetricians and Gynecologists.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Oral nifedipine<br>Oral medication 10mg and 20mg | Drug: Nifedipine<br>* Nifedipine 10mg oral will be given and the MAP will then be calculated 20 minutes after medication is given. If SBP is ≥160mmHg or DBP is ≥110mmHg, nifedipine 20mg oral will be given and the MAP will then be calculated 20 minutes after medication is given. If SBP is ≥160mmHg or DBP is ≥110mmHg, nifedipine 20mg oral will be given and the MAP will then be calculated 20 minutes after medication is given and institution specific protocol will be performed.<br>|
| Other: Intravenous labetalol<br>intravenous medication 20mg, 40mg, 80 mg | Drug: Labetalol<br>* Labetalol 20mg IV will be given over 2 minutes and the MAP will then be calculated 10 minutes after medication is given. If SBP is ≥160mmHg or DBP is ≥110mmHg, labetalol 40mg IV will be given over 2 minutes and the MAP will then be calculated 10 minutes after medication is given. If SBP is ≥160mmHg or DBP is ≥110mmHg, labetalol 80mg IV will be given over 2 minutes and the MAP will then be calculated 10 minutes after medication is given. If SBP is ≥160mmHg or DBP is ≥110mmHg, then another medication will be chosen based on institution specific protocol.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Achieve Non Severe Range Blood Pressure | Time to achieve goal blood pressure, that is, non severe range blood pressures after medication received. | Ten minute intervals from the time of the first severe range blood pressure, up to 1 hour | 
| Number of Participants to Achieve Non Severe Range Blood Pressure | Number of participants by ethnicity to achieve goal blood pressure, that is, non severe range blood pressures after medication received. | up to 1 hour | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Genetic Variants of Genes | the frequency of variant alleles in different receptors involved in the response to labetalol and nifedipine administration in the pregnant and postpartum population. | up to 1 year | 
| Number of Participants With Medication Side Effects | Number of participants with side effect profile to assess the rate of side effects from IV labetalol and oral nifedipine | assessed 10 minutes to 1 hour after medication is given | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypertension, Pregnancy-induced, Pregnancy Induced Hypertension, Gestational Hypertension, Transient Hypertension, Pregnancy, Pharmacogenetics