Response to Anti-hypertensives in Pregnant and Postpartum Patients

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

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.

Study Overview

• Status: Completed
• Conditions: Preeclampsia; Hypertension in Pregnancy
• Intervention / Treatment: Drug: Nifedipine; Drug: Labetalol

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 109
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • Brooklyn, New York, United States, 11219
      • Maimonides Hospital
    • New York, New York, United States, 10019
      • Mount Sinai West

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 53 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Oral nifedipine; Oral medication 10mg and 20mg	Drug: Nifedipine; 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.
Other: Intravenous labetalol; intravenous medication 20mg, 40mg, 80 mg	Drug: Labetalol; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Icahn School of Medicine at Mount Sinai
• Collaborators: Maimonides Medical Center; Mount Sinai Hospital, New York
• Investigators: Study Director: Lois Brustman, MD, Icahn School of Medicine at Mount Sinai; Study Director: Howard Minkoff, MD, Icahn School of Medicine at Mount Sinai; Principal Investigator: Poroshat Shekarloo, MD, Icahn School of Medicine at Mount Sinai

Study record dates

Study Major Dates

• Study Start (Actual): September 11, 2017
• Primary Completion (Actual): April 5, 2019
• Study Completion (Actual): April 5, 2019

Study Registration Dates

• First Submitted: April 13, 2018
• First Submitted That Met QC Criteria: April 23, 2018
• First Posted (Actual): April 24, 2018

Study Record Updates

• Last Update Posted (Actual): May 24, 2021
• Last Update Submitted That Met QC Criteria: April 30, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Pharmacogenetics; Gestational Hypertension; Pregnancy Induced Hypertension; Hypertension, Pregnancy-induced; Transient Hypertension, Pregnancy
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Pregnancy Complications; Hypertension; Pre-Eclampsia; Hypertension, Pregnancy-Induced; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Reproductive Control Agents; Calcium Channel Blockers; Tocolytic Agents; Sympathomimetics; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Nifedipine; Labetalol
• Other Study ID Numbers: GCO 17-0257; Maimonides IRB 2018-02-17 (Other Identifier: Maimonides IRB/Research Committee)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No