Gestational Hypertension, Hypertension in Pregnancy, Postpartum, Postpartum Preeclampsia, Preeclampsia Severe
Conditions
Brief summary
This study evaluates whether nifedipine or enalapril is better at decreasing the amount of medical resources used in the postpartum period by women who have high blood pressure in pregnancy and the postpartum period. Half of participants will receive enalapril while the other half will receive enalapril. We will compare the two groups in the amount of medical resources used which we are defining as prolonged hospitalizations, unscheduled medical visits and/or hospital readmissions in the postpartum period.
Detailed description
This is randomized controlled trial to investigate if enalapril is superior to nifedipine in terms of medical resources used in postpartum women with hypertension. These are both antihypertensives we commonly use in the postpartum period for women with hypertension in pregnancy but we do not know which medication works better at decreasing prolonged hospitalizations, the number of unscheduled medical visits and/or readmissions to the hospital. Nifedipine is more traditionally used and well-validated by current medical literature. However, enalapril's mechanism of action is better suited to the dysregulation of blood pressure that can occur with hypertensive disorders of pregnancy. Therefore, we hypothesize that enalapril is superior to nifedipine in terms of medical resources used in the postpartum period.
Interventions
DRUGNIFEdipine ER
Postpartum women with high blood pressure will be randomized to receive nifedipine extended release 30mg daily as their starting antihypertensive.
DRUGEnalapril
Postpartum women with high blood pressure will be randomized to receive enalapril 10 mg daily as their starting antihypertensive.
Sponsors
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* diagnosis of any hypertensive disorder of pregnancy/postpartum period or chronic hypertension * provider wanting to initiate antihypertensive in the postpartum period * the patient is not currently on \>1 antihypertensive * plans to receive postpartum care at the hospital or affiliated clinic
Exclusion criteria
* sustained pulse \<60 or \>120 BPM over four hours * allergy to any of the antihypertensives * creatinine greater than or equal to 1.5 * strict contraindication to any of the antihypertensives * history of failed treatment with any of the antihypertensives
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Prolonged Hospitalization | up to six weeks postpartum | Participants who have any postpartum hospitalization that extends beyond the normal length of stay after delivery |
| Unscheduled Clinic Appointment | up to six weeks postpartum | Participants who have any additional clinic appointments for any clinical reason in the postpartum period beyond the two appointments (around 1 week and 6 weeks postpartum) that are routinely scheduled |
| Visit to Labor and Delivery Triage for Evaluation | up to six weeks postpartum | Participants who have any visit to triage on Labor and Delivery for evaluation in the postpartum period for any clinical reason |
| Postpartum Readmission | up to six weeks postpartum | Participants who have any postpartum readmission after being discharged from the delivery hospitalization in the postpartum period |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Creatinine Values at 1-2 Weeks After Discharge | 1-2 weeks | Creatinine measured at 1-2 weeks after discharge from the randomization hospitalization (not all study patients attended their appointments and had their blood drawn) |
| Continued Need for Antihypertensive | up to six weeks postpartum | If a patient still needs the prescribed antihypertensives one week after discharge and six weeks after delivery to control her blood pressure as determined by her provider during her clinic visit |
| Time to Blood Pressure Control | up to six weeks postpartum | Time to sustained blood pressure control (defined as no need for changes to antihypertensive regimen for \>24 hours) |
| Patient Self-reported Compliance With Their Antihypertensive Regimen | up to six weeks postpartum | The patient will complete a survey that self-assesses how compliant she has been with taking the prescribed antihypertensives (difficulty remembering to take the medication) |
| Creatinine Level Around 6 Weeks After Delivery | 6 weeks after delivery | Creatinine level drawn at 6 week postpartum visit (not all study patients attended their appointments and had their blood drawn) |
| Number of Participants With Self-reported Side Effects Attributed to the Antihypertensive They Received | up to six weeks postpartum | A patient will complete a survey that will report any side effect the patient attributes to the antihypertension medication |
| Number of Participants Who Needed for Additional Antihypertensives | up to six weeks postpartum | Any time a patient needs a second or third agent added to her antihypertensive regimen |
| Time to Discharge | up to six weeks postpartum | The days a patient stays in the hospital after delivery or after readmission for postpartum hypertension |
| Clinically Significant Hypotension or Hypertension | up to six weeks postpartum | Any time a patient became symptomatic from her blood pressure as noted by her providers |
Countries
United States
Participant flow
Recruitment details
We enrolled 94 participants in the study.
Pre-assignment details
We aimed for 90 participants as part of the protocol but ended up oversampling at 94 due to concern over potential drop out.
Participants by arm
| Arm | Count |
|---|---|
| Nifedipine Participants in the nifedipine group were assigned nifedipine ER 30mg daily as their initial antihypertensive. | 47 |
| Enalapril Participants in the nifedipine group were assigned enalapril 10mg daily as their initial antihypertensive. | 47 |
| Total | 94 |
Baseline characteristics
| Characteristic | Total | Nifedipine | Enalapril |
|---|---|---|---|
| Age, Continuous | 32.8 years STANDARD_DEVIATION 6.5 | 33.3 years STANDARD_DEVIATION 6.3 | 32.4 years STANDARD_DEVIATION 6.7 |
| BMI | 34.9 kg/m^2 STANDARD_DEVIATION 7.5 | 34.6 kg/m^2 STANDARD_DEVIATION 8 | 35.2 kg/m^2 STANDARD_DEVIATION 7 |
| Delivery type Cesarean | 54 Participants | 29 Participants | 25 Participants |
| Delivery type Operative | 7 Participants | 6 Participants | 1 Participants |
| Delivery type Vaginal | 33 Participants | 12 Participants | 21 Participants |
| Gestational age at delivery | 36.9 weeks STANDARD_DEVIATION 2.6 | 36.6 weeks STANDARD_DEVIATION 2.3 | 37.4 weeks STANDARD_DEVIATION 2.9 |
| Hypertensive diagnosis Chronic | 6 Participants | 3 Participants | 3 Participants |
| Hypertensive diagnosis Gestational | 25 Participants | 16 Participants | 9 Participants |
| Hypertensive diagnosis Preeclampsia without severe features | 6 Participants | 2 Participants | 4 Participants |
| Hypertensive diagnosis Preeclampsia with severe features | 51 Participants | 21 Participants | 30 Participants |
| Hypertensive diagnosis Superimposed preeclampsia | 6 Participants | 5 Participants | 1 Participants |
| Insurance Private insurance | 58 Participants | 32 Participants | 26 Participants |
| Insurance Public insurance | 36 Participants | 15 Participants | 21 Participants |
| Parity | 1.87 para STANDARD_DEVIATION 1.7 | 1.89 para STANDARD_DEVIATION 1.6 | 1.85 para STANDARD_DEVIATION 1.7 |
| Race/Ethnicity, Customized Asian | 2 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Hispanic | 24 Participants | 9 Participants | 15 Participants |
| Race/Ethnicity, Customized Non-Hispanic Black | 28 Participants | 11 Participants | 17 Participants |
| Race/Ethnicity, Customized White | 40 Participants | 25 Participants | 15 Participants |
| Region of Enrollment United States | 94 participants | 47 participants | 47 participants |
| Sex: Female, Male Female | 94 Participants | 47 Participants | 47 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Twin gestation | 11 Participants | 9 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 47 | 0 / 47 |
| other Total, other adverse events | 0 / 47 | 0 / 47 |
| serious Total, serious adverse events | 0 / 47 | 0 / 47 |
Outcome results
Primary
Postpartum Readmission
Participants who have any postpartum readmission after being discharged from the delivery hospitalization in the postpartum period
Time frame: up to six weeks postpartum
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nifedipine | Postpartum Readmission | 3 Participants |
| Enalapril | Postpartum Readmission | 4 Participants |
Primary
Prolonged Hospitalization
Participants who have any postpartum hospitalization that extends beyond the normal length of stay after delivery
Time frame: up to six weeks postpartum
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nifedipine | Prolonged Hospitalization | 13 Participants |
| Enalapril | Prolonged Hospitalization | 17 Participants |
Primary
Unscheduled Clinic Appointment
Participants who have any additional clinic appointments for any clinical reason in the postpartum period beyond the two appointments (around 1 week and 6 weeks postpartum) that are routinely scheduled
Time frame: up to six weeks postpartum
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nifedipine | Unscheduled Clinic Appointment | 19 Participants |
| Enalapril | Unscheduled Clinic Appointment | 17 Participants |
Primary
Visit to Labor and Delivery Triage for Evaluation
Participants who have any visit to triage on Labor and Delivery for evaluation in the postpartum period for any clinical reason
Time frame: up to six weeks postpartum
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nifedipine | Visit to Labor and Delivery Triage for Evaluation | 13 Participants |
| Enalapril | Visit to Labor and Delivery Triage for Evaluation | 17 Participants |
Secondary
Clinically Significant Hypotension or Hypertension
Any time a patient became symptomatic from her blood pressure as noted by her providers
Time frame: up to six weeks postpartum
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nifedipine | Clinically Significant Hypotension or Hypertension | 0 Participants |
| Enalapril | Clinically Significant Hypotension or Hypertension | 0 Participants |
Secondary
Continued Need for Antihypertensive
If a patient still needs the prescribed antihypertensives one week after discharge and six weeks after delivery to control her blood pressure as determined by her provider during her clinic visit
Time frame: up to six weeks postpartum
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nifedipine | Continued Need for Antihypertensive | 41 Participants |
| Enalapril | Continued Need for Antihypertensive | 36 Participants |
Secondary
Creatinine Level Around 6 Weeks After Delivery
Creatinine level drawn at 6 week postpartum visit (not all study patients attended their appointments and had their blood drawn)
Time frame: 6 weeks after delivery
Population: This is the population who attended their 6 week postpartum visit and had a creatinine level drawn at that time
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nifedipine | Creatinine Level Around 6 Weeks After Delivery | 0.82 mg/dL | Standard Deviation 0.15 |
| Enalapril | Creatinine Level Around 6 Weeks After Delivery | 0.88 mg/dL | Standard Deviation 0.14 |
Secondary
Creatinine Values at 1-2 Weeks After Discharge
Creatinine measured at 1-2 weeks after discharge from the randomization hospitalization (not all study patients attended their appointments and had their blood drawn)
Time frame: 1-2 weeks
Population: This is the population of participants who attended a 1-2 week clinic visit after discharge and had a creatinine level drawn
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nifedipine | Creatinine Values at 1-2 Weeks After Discharge | 0.68 mg/dL | Standard Deviation 0.11 |
| Enalapril | Creatinine Values at 1-2 Weeks After Discharge | 0.75 mg/dL | Standard Deviation 0.17 |
Secondary
Number of Participants Who Needed for Additional Antihypertensives
Any time a patient needs a second or third agent added to her antihypertensive regimen
Time frame: up to six weeks postpartum
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nifedipine | Number of Participants Who Needed for Additional Antihypertensives | 6 Participants |
| Enalapril | Number of Participants Who Needed for Additional Antihypertensives | 16 Participants |
Secondary
Number of Participants With Self-reported Side Effects Attributed to the Antihypertensive They Received
A patient will complete a survey that will report any side effect the patient attributes to the antihypertension medication
Time frame: up to six weeks postpartum
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nifedipine | Number of Participants With Self-reported Side Effects Attributed to the Antihypertensive They Received | 1 Participants |
| Enalapril | Number of Participants With Self-reported Side Effects Attributed to the Antihypertensive They Received | 1 Participants |
Secondary
Patient Self-reported Compliance With Their Antihypertensive Regimen
The patient will complete a survey that self-assesses how compliant she has been with taking the prescribed antihypertensives (difficulty remembering to take the medication)
Time frame: up to six weeks postpartum
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nifedipine | Patient Self-reported Compliance With Their Antihypertensive Regimen | 0 Participants |
| Enalapril | Patient Self-reported Compliance With Their Antihypertensive Regimen | 2 Participants |
Secondary
Time to Blood Pressure Control
Time to sustained blood pressure control (defined as no need for changes to antihypertensive regimen for \>24 hours)
Time frame: up to six weeks postpartum
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nifedipine | Time to Blood Pressure Control | 0.7 days | Standard Deviation 1 |
| Enalapril | Time to Blood Pressure Control | 1.9 days | Standard Deviation 3.5 |
Secondary
Time to Discharge
The days a patient stays in the hospital after delivery or after readmission for postpartum hypertension
Time frame: up to six weeks postpartum
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nifedipine | Time to Discharge | 3.2 days | Standard Deviation 1.6 |
| Enalapril | Time to Discharge | 3.3 days | Standard Deviation 1.7 |