Hypertension in Pregnancy, Preeclampsia
Conditions
Keywords
Hypertension, Pregnancy-induced, Pregnancy Induced Hypertension, Gestational Hypertension, Transient Hypertension, Pregnancy, Pharmacogenetics
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).
Interventions
DRUGNifedipine
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.
DRUGLabetalol
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.
Sponsors
Maimonides Medical Center
Mount Sinai Hospital, New York
Icahn School of Medicine at Mount Sinai
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 55 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 |
Countries
United States
Participant flow
Recruitment details
This trial was conducted at two urban academic institutions with participants enrolled from September 2017 to April 2019.
Participants by arm
| Arm | Count |
|---|---|
| Intravenous Labetalol 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. | 55 |
| Oral Nifedipine 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. | 54 |
| Total | 109 |
Baseline characteristics
| Characteristic | Oral Nifedipine | Intravenous Labetalol | Total |
|---|---|---|---|
| Age, Continuous | 33.67 years STANDARD_DEVIATION 5.74 | 35.49 years STANDARD_DEVIATION 6.25 | 34.59 years STANDARD_DEVIATION 6.05 |
| Body Mass Index (BMI) | 29.84 kg/m^2 STANDARD_DEVIATION 6.54 | 27.89 kg/m^2 STANDARD_DEVIATION 6.36 | 28.86 kg/m^2 STANDARD_DEVIATION 6.5 |
| Family History of HTN | 29 Participants | 26 Participants | 55 Participants |
| Gestational age | 36.9 weeks | 37.4 weeks | 37.1 weeks |
| History of Smoking | 12 Participants | 9 Participants | 21 Participants |
| Number of participants who are Post-partum | 5 Participants | 2 Participants | 7 Participants |
| Number of Participants with Chronic Hypertension (CHTN) | 9 Participants | 9 Participants | 18 Participants |
| Number of Participants with Diabete Mellitus Type I or II | 2 Participants | 2 Participants | 4 Participants |
| Number of Participants with Gestational Hypertension (GHTN) | 14 Participants | 12 Participants | 26 Participants |
| Pre-medication, DiastolicBlood Pressure | 97.09 mmHg STANDARD_DEVIATION 10.28 | 94.18 mmHg STANDARD_DEVIATION 10.02 | 95.62 mmHg STANDARD_DEVIATION 10.21 |
| Pre-medication, Systolic Blood Pressure | 171.74 mmHg STANDARD_DEVIATION 11.19 | 173.96 mmHg STANDARD_DEVIATION 12.74 | 172.86 mmHg STANDARD_DEVIATION 11.99 |
| Race/Ethnicity, Customized Black | 22 Participants | 20 Participants | 42 Participants |
| Race/Ethnicity, Customized White, Asian, or Hispanic | 32 Participants | 35 Participants | 67 Participants |
| Sex: Female, Male Female | 54 Participants | 55 Participants | 109 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 55 | 0 / 54 |
| other Total, other adverse events | 0 / 55 | 1 / 54 |
| serious Total, serious adverse events | 0 / 55 | 0 / 54 |
Outcome results
Primary
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.
Time frame: up to 1 hour
Population: participants by ethnicity
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Intravenous Labetalol | Number of Participants to Achieve Non Severe Range Blood Pressure | White, Asian, and Hispanic | 33 Participants |
| Intravenous Labetalol | Number of Participants to Achieve Non Severe Range Blood Pressure | Black | 18 Participants |
| Oral Nifedipine | Number of Participants to Achieve Non Severe Range Blood Pressure | White, Asian, and Hispanic | 31 Participants |
| Oral Nifedipine | Number of Participants to Achieve Non Severe Range Blood Pressure | Black | 22 Participants |
Primary
Time to Achieve Non Severe Range Blood Pressure
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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intravenous Labetalol | Time to Achieve Non Severe Range Blood Pressure | 10 minutes |
| Oral Nifedipine | Time to Achieve Non Severe Range Blood Pressure | 20 minutes |
Secondary
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.
Time frame: up to 1 year
Population: data not collected
Secondary
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
Time frame: assessed 10 minutes to 1 hour after medication is given
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Intravenous Labetalol | Number of Participants With Medication Side Effects | Headache | 6 Participants |
| Intravenous Labetalol | Number of Participants With Medication Side Effects | Nausea | 3 Participants |
| Intravenous Labetalol | Number of Participants With Medication Side Effects | Vomiting | 2 Participants |
| Intravenous Labetalol | Number of Participants With Medication Side Effects | Dizziness | 8 Participants |
| Intravenous Labetalol | Number of Participants With Medication Side Effects | Flushing | 7 Participants |
| Intravenous Labetalol | Number of Participants With Medication Side Effects | Any of the above | 18 Participants |
| Oral Nifedipine | Number of Participants With Medication Side Effects | Flushing | 7 Participants |
| Oral Nifedipine | Number of Participants With Medication Side Effects | Headache | 10 Participants |
| Oral Nifedipine | Number of Participants With Medication Side Effects | Dizziness | 4 Participants |
| Oral Nifedipine | Number of Participants With Medication Side Effects | Nausea | 7 Participants |
| Oral Nifedipine | Number of Participants With Medication Side Effects | Any of the above | 15 Participants |
| Oral Nifedipine | Number of Participants With Medication Side Effects | Vomiting | 3 Participants |