Response to Anti-hypertensives in Pregnant and Postpartum Patients

• Sponsor: Icahn School of Medicine at Mount Sinai (Other)
• Overall Status: Completed
• CT.gov ID: NCT03506724
• Collaborator: Mount Sinai Hospital, New York (Other), Maimonides Medical Center (Other)
• Enrollment: 109
• Locations: 2
• Arms: 2
• Actual Duration (Months): 18.8
• Patients Per Site: 54.5
• Patients Per Site Per Month: 2.9

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Hypertension in Pregnancy; Preeclampsia	Drug: Nifedipine; Drug: Labetalol	Phase 4

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 Design

• Study Type: Interventional
• Actual Enrollment: 109 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention 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.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)
• Primary Purpose: Treatment
• Official Title: Ethnic Differences in Anti-Hypertensive Medication Response Among Pregnant and Postpartum Patients
• Actual Study Start Date: Sep 11, 2017
• Actual Primary Completion Date: Apr 5, 2019
• Actual Study Completion Date: Apr 5, 2019

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. Time to Achieve Non Severe Range Blood Pressure [Ten minute intervals from the time of the first severe range blood pressure, up to 1 hour]

   Time to achieve goal blood pressure, that is, non severe range blood pressures after medication received.

2. Number of Participants to Achieve Non Severe Range Blood Pressure [up to 1 hour]

   Number of participants by ethnicity to achieve goal blood pressure, that is, non severe range blood pressures after medication received.

Secondary Outcome Measures

1. Frequency of Genetic Variants of Genes [up to 1 year]

   the frequency of variant alleles in different receptors involved in the response to labetalol and nifedipine administration in the pregnant and postpartum population.

2. Number of Participants With Medication Side Effects [assessed 10 minutes to 1 hour after medication is given]

   Number of participants with side effect profile to assess the rate of side effects from IV labetalol and oral nifedipine

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Maimonides Hospital	Brooklyn	New York	United States	11219
2	Mount Sinai West	New York	New York	United States	10019

Sponsors and Collaborators

• Icahn School of Medicine at Mount Sinai
• Mount Sinai Hospital, New York
• Maimonides Medical Center

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 Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 1, 2017

More Information

Publications

None provided.

• Responsible Party: Dyese Taylor, Principal Investigator, Icahn School of Medicine at Mount Sinai
• ClinicalTrials.gov Identifier: NCT03506724
• Other Study ID Numbers: GCO 17-0257; Maimonides IRB 2018-02-17
• First Posted: Apr 24, 2018
• Last Update Posted: May 24, 2021
• Last Verified: Apr 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Dyese Taylor, Principal Investigator, Icahn School of Medicine at Mount Sinai: Hypertension, Pregnancy-induced; Pregnancy Induced Hypertension; Gestational Hypertension; Transient Hypertension, Pregnancy; Pharmacogenetics
• Additional relevant MeSH terms: Pre-Eclampsia; Hypertension, Pregnancy-Induced; Hypertension; Labetalol; Nifedipine

Study Results

Participant Flow

Recruitment Details	This trial was conducted at two urban academic institutions with participants enrolled from September 2017 to April 2019.

Arm/Group Title	Oral Nifedipine	Intravenous Labetalol
Arm/Group Description	Oral medication 10mg and 20mg Nifedipine: Nifedipine 10mg oral given and the MAP calculated 20 minutes after medication is given. If SBP is ≥160mmHg or DBP is ≥110mmHg, nifedipine 20mg oral given and the MAP calculated 20 minutes after medication is given. If SBP is ≥160mmHg or DBP is ≥110mmHg, nifedipine 20mg oral given and the MAP calculated 20 minutes after medication is given and institution specific protocol performed.	Intravenous medication 20mg, 40mg, 80 mg Labetalol: Labetalol 20mg IV given over 2 minutes and the MAP calculated 10 minutes after medication is given. If SBP is ≥160mmHg or DBP is ≥110mmHg, labetalol 40mg IV given over 2 minutes and the MAP calculated 10 minutes after medication is given. If SBP is ≥160mmHg or DBP is ≥110mmHg, labetalol 80mg IV given over 2 minutes and the MAP calculated 10 minutes after medication is given. If SBP is ≥160mmHg or DBP is ≥110mmHg, then another medication chosen based on institution specific protocol.
Period Title: Overall Study
STARTED	54	55
COMPLETED	54	55
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Intravenous Labetalol	Oral Nifedipine	Total
Arm/Group Description	intravenous medication 20mg, 40mg, 80 mg Labetalol: Labetalol 20mg IV given over 2 minutes and the MAP calculated 10 minutes after medication is given. If SBP is ≥160mmHg or DBP is ≥110mmHg, labetalol 40mg IV given over 2 minutes and the MAP calculated 10 minutes after medication is given. If SBP is ≥160mmHg or DBP is ≥110mmHg, labetalol 80mg IV given over 2 minutes and the MAP calculated 10 minutes after medication is given. If SBP is ≥160mmHg or DBP is ≥110mmHg, then another medication chosen based on institution specific protocol.	Oral medication 10mg and 20mg Nifedipine: Nifedipine 10mg oral given and the MAP calculated 20 minutes after medication is given. If SBP is ≥160mmHg or DBP is ≥110mmHg, nifedipine 20mg oral given and the MAP calculated 20 minutes after medication is given. If SBP is ≥160mmHg or DBP is ≥110mmHg, nifedipine 20mg oral given and the MAP calculated 20 minutes after medication is given and institution specific protocol performed.	Total of all reporting groups
Overall Participants	55	54	109
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	35.49 (6.25)	33.67 (5.74)	34.59 (6.05)
Sex: Female, Male (Count of Participants)
Female	55 100%	54 100%	109 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
Black	20 36.4%	22 40.7%	42 38.5%
White, Asian, or Hispanic	35 63.6%	32 59.3%	67 61.5%
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	27.89 (6.36)	29.84 (6.54)	28.86 (6.50)
Gestational age (weeks) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [weeks]	37.4	36.9	37.1
Number of participants who are Post-partum (Count of Participants)
Count of Participants [Participants]	2 3.6%	5 9.3%	7 6.4%
Number of Participants with Chronic Hypertension (CHTN) (Count of Participants)
Count of Participants [Participants]	9 16.4%	9 16.7%	18 16.5%
Number of Participants with Gestational Hypertension (GHTN) (Count of Participants)
Count of Participants [Participants]	12 21.8%	14 25.9%	26 23.9%
Number of Participants with Diabete Mellitus Type I or II (Count of Participants)
Count of Participants [Participants]	2 3.6%	2 3.7%	4 3.7%
Family History of HTN (Count of Participants)
Count of Participants [Participants]	26 47.3%	29 53.7%	55 50.5%
History of Smoking (Count of Participants)
Count of Participants [Participants]	9 16.4%	12 22.2%	21 19.3%
Pre-medication, Systolic Blood Pressure (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	173.96 (12.74)	171.74 (11.19)	172.86 (11.99)
Pre-medication, DiastolicBlood Pressure (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	94.18 (10.02)	97.09 (10.28)	95.62 (10.21)

Outcome Measures

1. Primary Outcome

Title	Time to Achieve Non Severe Range Blood Pressure
Description	Time to achieve goal blood pressure, that is, non severe range blood pressures after medication received.
Time Frame	Ten minute intervals from the time of the first severe range blood pressure, up to 1 hour

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intravenous Labetalol	Oral Nifedipine
Arm/Group Description	intravenous medication 20mg, 40mg, 80 mg Labetalol: Labetalol 20mg IV given over 2 minutes and the MAP calculated 10 minutes after medication is given. If SBP is ≥160mmHg or DBP is ≥110mmHg, labetalol 40mg IV given over 2 minutes and the MAP calculated 10 minutes after medication is given. If SBP is ≥160mmHg or DBP is ≥110mmHg, labetalol 80mg IV given over 2 minutes and the MAP calculated 10 minutes after medication is given. If SBP is ≥160mmHg or DBP is ≥110mmHg, then another medication chosen based on institution specific protocol.	Oral medication 10mg and 20mg Nifedipine: Nifedipine 10mg oral given and the MAP calculated 20 minutes after medication is given. If SBP is ≥160mmHg or DBP is ≥110mmHg, nifedipine 20mg oral given and the MAP calculated 20 minutes after medication is given. If SBP is ≥160mmHg or DBP is ≥110mmHg, nifedipine 20mg oral given and the MAP calculated 20 minutes after medication is given and institution specific protocol performed.
Measure Participants	55	54
Median (Inter-Quartile Range) [minutes]	10	20

2. Primary Outcome

Title	Number of Participants to Achieve Non Severe Range Blood Pressure
Description	Number of participants by ethnicity to achieve goal blood pressure, that is, non severe range blood pressures after medication received.
Time Frame	up to 1 hour

Outcome Measure Data

Analysis Population Description

participants by ethnicity

Arm/Group Title	Intravenous Labetalol	Oral Nifedipine
Arm/Group Description	intravenous medication 20mg, 40mg, 80 mg Labetalol: Labetalol 20mg IV given over 2 minutes and the MAP calculated 10 minutes after medication is given. If SBP is ≥160mmHg or DBP is ≥110mmHg, labetalol 40mg IV given over 2 minutes and the MAP calculated 10 minutes after medication is given. If SBP is ≥160mmHg or DBP is ≥110mmHg, labetalol 80mg IV given over 2 minutes and the MAP calculated 10 minutes after medication is given. If SBP is ≥160mmHg or DBP is ≥110mmHg, then another medication chosen based on institution specific protocol.	Oral medication 10mg and 20mg Nifedipine: Nifedipine 10mg oral given and the MAP calculated 20 minutes after medication is given. If SBP is ≥160mmHg or DBP is ≥110mmHg, nifedipine 20mg oral given and the MAP calculated 20 minutes after medication is given. If SBP is ≥160mmHg or DBP is ≥110mmHg, nifedipine 20mg oral given and the MAP calculated 20 minutes after medication is given and institution specific protocol performed.
Measure Participants	55	54
White, Asian, and Hispanic	33 60%	31 57.4%
Black	18 32.7%	22 40.7%

3. Secondary Outcome

Title	Frequency of Genetic Variants of Genes
Description	the frequency of variant alleles in different receptors involved in the response to labetalol and nifedipine administration in the pregnant and postpartum population.
Time Frame	up to 1 year

Outcome Measure Data

Analysis Population Description

data not collected

Arm/Group Title	Intravenous Labetalol	Oral Nifedipine
Arm/Group Description	intravenous medication 20mg, 40mg, 80 mg Labetalol: Labetalol 20mg IV given over 2 minutes and the MAP calculated 10 minutes after medication is given. If SBP is ≥160mmHg or DBP is ≥110mmHg, labetalol 40mg IV given over 2 minutes and the MAP calculated 10 minutes after medication is given. If SBP is ≥160mmHg or DBP is ≥110mmHg, labetalol 80mg IV given over 2 minutes and the MAP calculated 10 minutes after medication is given. If SBP is ≥160mmHg or DBP is ≥110mmHg, then another medication chosen based on institution specific protocol.	Oral medication 10mg and 20mg Nifedipine: Nifedipine 10mg oral given and the MAP calculated 20 minutes after medication is given. If SBP is ≥160mmHg or DBP is ≥110mmHg, nifedipine 20mg oral given and the MAP calculated 20 minutes after medication is given. If SBP is ≥160mmHg or DBP is ≥110mmHg, nifedipine 20mg oral given and the MAP calculated 20 minutes after medication is given and institution specific protocol performed.
Measure Participants	0	0

4. Secondary Outcome

Title	Number of Participants With Medication Side Effects
Description	Number of participants with side effect profile to assess the rate of side effects from IV labetalol and oral nifedipine
Time Frame	assessed 10 minutes to 1 hour after medication is given

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intravenous Labetalol	Oral Nifedipine
Arm/Group Description	intravenous medication 20mg, 40mg, 80 mg Labetalol: Labetalol 20mg IV given over 2 minutes and the MAP calculated 10 minutes after medication is given. If SBP is ≥160mmHg or DBP is ≥110mmHg, labetalol 40mg IV given over 2 minutes and the MAP calculated 10 minutes after medication is given. If SBP is ≥160mmHg or DBP is ≥110mmHg, labetalol 80mg IV given over 2 minutes and the MAP calculated 10 minutes after medication is given. If SBP is ≥160mmHg or DBP is ≥110mmHg, then another medication chosen based on institution specific protocol.	Oral medication 10mg and 20mg Nifedipine: Nifedipine 10mg oral given and the MAP calculated 20 minutes after medication is given. If SBP is ≥160mmHg or DBP is ≥110mmHg, nifedipine 20mg oral given and the MAP calculated 20 minutes after medication is given. If SBP is ≥160mmHg or DBP is ≥110mmHg, nifedipine 20mg oral given and the MAP calculated 20 minutes after medication is given and institution specific protocol performed.
Measure Participants	55	54
Headache	6 10.9%	10 18.5%
Nausea	3 5.5%	7 13%
Vomiting	2 3.6%	3 5.6%
Dizziness	8 14.5%	4 7.4%
Flushing	7 12.7%	7 13%
Any of the above	18 32.7%	15 27.8%

Adverse Events

Time Frame	1 hour
Arm/Group Title	Intravenous Labetalol		Oral Nifedipine
Arm/Group Description	intravenous medication 20mg, 40mg, 80 mg Labetalol: Labetalol 20mg IV given over 2 minutes and the MAP calculated 10 minutes after medication is given. If SBP is ≥160mmHg or DBP is ≥110mmHg, labetalol 40mg IV given over 2 minutes and the MAP calculated 10 minutes after medication is given. If SBP is ≥160mmHg or DBP is ≥110mmHg, labetalol 80mg IV given over 2 minutes and the MAP calculated 10 minutes after medication is given. If SBP is ≥160mmHg or DBP is ≥110mmHg, then another medication chosen based on institution specific protocol.		Oral medication 10mg and 20mg Nifedipine: Nifedipine 10mg oral given and the MAP calculated 20 minutes after medication is given. If SBP is ≥160mmHg or DBP is ≥110mmHg, nifedipine 20mg oral given and the MAP calculated 20 minutes after medication is given. If SBP is ≥160mmHg or DBP is ≥110mmHg, nifedipine 20mg oral given and the MAP calculated 20 minutes after medication is given and institution specific protocol performed.
All Cause Mortality
	Intravenous Labetalol		Oral Nifedipine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/55 (0%)		0/54 (0%)
Serious Adverse Events
	Intravenous Labetalol		Oral Nifedipine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/55 (0%)		0/54 (0%)
Other (Not Including Serious) Adverse Events
	Intravenous Labetalol		Oral Nifedipine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/55 (0%)		1/54 (1.9%)
Pregnancy, puerperium and perinatal conditions
symptomatic hypotenstion	0/55 (0%)		1/54 (1.9%)

Limitations/Caveats

Small sample size and the study was not double blind

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.