Clinical trial NCT03506724
Conditions: Hypertension in Pregnancy Preeclampsia
Keywords: Hypertension, Pregnancy-induced Pregnancy Induced Hypertension Gestational Hypertension Transient Hypertension, Pregnancy Pharmacogenetics
Sponsor: Icahn School of Medicine at Mount Sinai
Start date: 2017-09-11; Completion date: 2019-04-05
Enrollment: 109 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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.

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).

Arms: arm 1: Oral medication 10mg and 20mg arm 2: intravenous medication 20mg, 40mg, 80 mg
Interventions: intervention 1: Nifedipine intervention 2: Labetalol
Intervention descriptions: intervention 1: 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. intervention 2: 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.

Protocol documents:
Prot_SAP_000.pdf: 
 
Ethnic Differences in Antihypertensive Medication Response 
among Pregnant and Postpartum Patients 
 
Dyese Taylor, MD 
 
NCT03506724 
 
11/2017 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
 
 
 
 
 
Protocol 
 
Patients were randomized to first receive IV labetalol or oral nifedipine and the number 
of doses of each medication that was given was recorded. The protocol used for medication 
administration was the same as the ACOG protocol for treatment of acute hypertension in 
pregnancy (See medication specific protocol below). Blood pressure for all women in the study 
was taken in the right arm with an automated blood pressure cuff while the patient was resting in 
bed in the semi-recumbent position. The systolic blood pressure and diastolic blood pressure was 
recorded before and after administration of each medication. A short survey to assess patient-
reported side effects were provided prior to and post medication administration. 
 
IV Labetalol protocol 
Labetalol 20mg IV was given over 2 minutes and the systolic and diastolic blood pressures were 
recorded 10 minutes after the medication was given. If SBP was ≥160mmHg or DBP was 
≥110mmHg, labetalol 40mg IV was given over 2 minutes and the systolic and diastolic blood 
pressures were recorded 10 minutes after the medication was given. If SBP was ≥160mmHg or 
DBP was ≥110mmHg, labetalol 80mg IV was given over 2 minutes and the systolic and diastolic 
blood pressures were recorded 10 minutes after the medication was given. If SBP was 
≥160mmHg or DBP was ≥110mmHg, then another medication was chosen based on institution 
specific protocol. (ACOG Safe Motherhood Initiative) 
 
Oral nifedipine protocol 
Nifedipine 10mg oral was given and the systolic and diastolic blood pressures were recorded 20 
minutes after the medication was given. If SBP was ≥160mmHg or DBP was ≥110mmHg, 


nifedipine 20mg oral was given and the systolic and diastolic blood pressures were recorded 20 
minutes after medication was given. If SBP is ≥160mmHg or DBP is ≥110mmHg, nifedipine 
20mg oral was given and the systolic and diastolic blood pressures were recorded 20 minutes 
after medication was given. If SBP was ≥160mmHg or DBP was ≥110mmHg, then another 
medication was chosen based on institution specific protocol. (ACOG Safe Motherhood 
Initiative) 
 
Statistical Analysis 
In the following sample size calculation, our primary aim is to detect an interaction effect 
between race and hypertensive treatment on time to reach goal blood pressure. We assume 
that the race distribution would be 20% for African Americans and 80% for Caucasians or Asians 
entering the clinic during the trial enrollment period. Randomization will be stratified by race at 
a 1:1 ratio to Nifedipine or Labetalol.  
We assume the minimally clinical difference for African American patients on Labetalol is 
expected to take 30 minutes longer compared to patients on Nifedipine to reach their goal 
blood pressure. For Caucasian or Asian patients, those on Labetalol are expected to take 20 
minutes longer compared to those on Nifedipine to reach their goal blood pressure. We expect 
residuals to be normally distributed with a mean of 0 and standard error of 8. We assume that 
time to goal blood pressure is normally distributed and power to detect an interaction by a 
linear regression is at least 85% with an alpha of 0.05.  
Based on the above, we used a simulation approach to estimate that we would need a total of 
146 patients to provide at least 85% power to detect an interaction effect between race and 
hypertensive treatment.  
Power 
Assumed Effect 
Size for African 
Americans 
Assumed 
Effect Size for 
Caucasians or 
Asians 
Assume 
Proportion of 
African 
Americans 
Minimal 
Number 
of African 
Americans 
Minimal 
Number of 
Caucasians 
or Asians 
Total N 
0.85 
30 min 
20 min 
40% 
40 
58 
98 
0.90 
30 min 
20 min 
40% 
46 
68 
114