Hypertension, Hypertension, Pregnancy-Induced, Postpartum Preeclampsia, Postpartum Pregnancy-Induced Hypertension
Conditions
Keywords
De novo postpartum hypertension, New-onset postpartum hypertension, Lasix, Furosemide
Brief summary
Primary objective: To evaluate whether oral furosemide can help prevent de novo postpartum hypertension (new-onset high blood pressure after delivery) by reducing blood pressure after delivery in high-risk women. Secondary objectives: To evaluate whether oral furosemide administered to high-risk women after delivery can reduce the frequency of postpartum hypertensive episodes, the need for antihypertensive therapy, the risk of postpartum preeclampsia, and the incidence of severe maternal morbidity.
Detailed description
Hypertensive disorders of pregnancy are one of the leading causes of maternal morbidity and mortality worldwide. The majority of clinical research has focused on pregnancy-related hypertension that develops in the antenatal period, while studies of the incidence, risk factors, and prevention of postpartum hypertension are limited. In particular, there is a paucity of data about the clinical entity known as de novo postpartum hypertension, in which women who are normotensive throughout pregnancy and delivery subsequently go on to develop high blood pressure in the immediate to late postpartum period. Of those with postpartum preeclampsia, 33-69% were normotensive antepartum. Early identification and treatment of antepartum preeclampsia has been shown to decrease some severe maternal outcomes. Conversely, women with de novo postpartum hypertensive disorders remain among the highest risk for severe maternal morbidity due to decreased surveillance and lack of data regarding preventive therapies and interventions. Evidence from multiple randomized controlled trials have demonstrated a benefit in the use of oral loop-diuretics in decreasing postpartum systolic blood pressure, promoting faster normalization of blood pressure, and decreasing the need for antihypertensive therapy in women with an antenatal diagnosis of preeclampsia. Biological plausibility suggests that loop-diuretic therapy may similarly mitigate the normal physiologic mechanism that has been implicated in the pathogenesis of hypertensive complications after delivery in women at risk for de novo postpartum hypertension. This study is a double-blind randomized placebo-controlled trial of 82 high-risk women to assess whether treatment with oral Lasix (furosemide) after delivery reduces blood pressure at the time of discharge. Women at high risk for de novo postpartum hypertension will be randomized to a five-day course of either 20 mg oral Lasix (furosemide) or placebo once daily initiated after delivery. Women will be monitored through their routine 2-week and 6-week postpartum visits, during which times hypertensive complications and adverse effects of therapy will be assessed.
Interventions
DRUGFurosemide
Furosemide 20 mg pill taken daily for 5 days
OTHERPlacebo
Identical-appearing placebo pill taken daily for 5 days
Sponsors
Columbia University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Consenting women will be assigned to Lasix (furosemide) or placebo in a 1:1 ratio according to a randomization scheme achieved using a computer generated algorithm. Neither the participant nor the clinical care team will be aware of the allocation arm.
Intervention model description
The study is a randomized controlled clinical trial of 82 women with one or more high-risk factors for de novo postpartum hypertension, randomized to one of two arms: 20 mg PO Lasix (furosemide) daily for 5 days or identical-appearing daily placebo for 5 days.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Postpartum women * No antenatal diagnosis of hypertensive disorder of pregnancy at the time of admission for delivery, defined as existing chronic hypertension diagnosis or documented blood pressure of ≥140 systolic OR ≥90 diastolic on at least 2 occasions at least 4 hours apart prior to delivery admission who do not go on to get magnesium for seizure prophylaxis by the time of delivery * At least 18 years of age * English or Spanish speakers * One or more high risk factors for development of de novo postpartum hypertension
Exclusion criteria
* Non-English or Spanish speakers * Women with a contraindication to diuretic therapy * Women who have used diuretics in the two weeks prior to delivery
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Arterial Blood Pressure (MAP) | 24 hours prior to discharge through discharge, up to 7 days | Difference in MAP averaged over the 24 hours prior to discharge or the 24 hours prior to antihypertensive therapy initiation (whichever occurs first) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of de Novo Postpartum Preeclampsia | Discharge (up to 7 days), 2 weeks postpartum, 6 weeks postpartum | Number of participants who develop de novo postpartum hypertension. This outcome was assessed at Discharge (up to 7 days), 2 weeks postpartum, and 6 weeks postpartum. Data is reported at 6 weeks postpartum. |
| Percent of Recorded Blood Pressures That Are Elevated | Discharge (up to 7 days), 2 weeks postpartum, 6 weeks postpartum | Percent of recorded blood pressures that are elevated (\>140 systolic OR \>90 diastolic). |
| Rate of Magnesium Sulfate Administration | Discharge (up to 7 days), 2 weeks postpartum, 6 weeks postpartum | Number of participants who receive intravenous magnesium sulfate for seizure prophylaxis. This outcome was assessed at Discharge (up to 7 days), 2 weeks postpartum, and 6 weeks postpartum. Data is reported at 6 weeks postpartum. |
| Time to Discharge | Randomization through discharge, up to 7 days | Time until discharge from the hospital |
| Rate of Severe Maternal Morbidity | Discharge (up to 7 days), 2 weeks postpartum, 6 weeks postpartum | Number of participants experiencing severe maternal morbidity (e.g. seizure, stroke, Posterior reversible encephalopathy syndrome (PRES), death, etc.) This outcome was assessed at Discharge (up to 7 days), 2 weeks postpartum, and 6 weeks postpartum. Data is reported at 6 weeks postpartum. |
| Rate of Triage or Emergency Department (ED) Presentation/Readmission | 2 weeks postpartum, 6 weeks postpartum | Number of participants who experienced triage or ED presentation/readmission for hypertensive-related complaints. This outcome was assessed at 2 weeks postpartum and 6 weeks postpartum. Data is reported at 6 weeks postpartum. |
| Breastfeeding Continuation Rate | 2 weeks postpartum, 6 weeks postpartum | Number of participants continuing to breastfeed of those who initiated breastfeeding after delivery. This outcome was assessed at Discharge (up to 7 days), 2 weeks postpartum, and 6 weeks postpartum. Data is reported at 2 weeks and 6 weeks postpartum. |
| Rate of Initiation of Antihypertensives | Discharge (up to 7 days), 2 weeks postpartum, 6 weeks postpartum | Number of participants receiving intravenous antihypertensive therapy and initiated on oral hypertensive therapy. This outcome was assessed at Discharge (up to 7 days), 2 weeks postpartum, and 6 weeks postpartum. Data is reported at 6 weeks postpartum. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lasix (Furosemide) Furosemide 20 mg, oral, once daily for 5 days
Furosemide: Furosemide 20 mg pill taken daily for 5 days | 40 |
| Placebo Identical-appearing placebo, oral, once daily for 5 days
Placebo: Identical-appearing placebo pill taken daily for 5 days | 40 |
| Total | 80 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Lasix (Furosemide) | Total | Placebo |
|---|---|---|---|
| Age, Customized age < 35 | 17 Participants | 29 Participants | 12 Participants |
| Age, Customized age >= 35 | 23 Participants | 51 Participants | 28 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants | 21 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants | 49 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 6 Participants | 10 Participants | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 10 Participants | 9 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 10 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 9 Participants | 9 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 15 Participants | 25 Participants | 10 Participants |
| Race (NIH/OMB) White | 14 Participants | 26 Participants | 12 Participants |
| Region of Enrollment United States | 40 participants | 80 participants | 40 participants |
| Sex: Female, Male Female | 40 Participants | 80 Participants | 40 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 / 40 | 0 / 40 |
| other Total, other adverse events | 0 / 40 | 0 / 40 |
| serious Total, serious adverse events | 0 / 40 | 0 / 40 |
Outcome results
Primary
Mean Arterial Blood Pressure (MAP)
Difference in MAP averaged over the 24 hours prior to discharge or the 24 hours prior to antihypertensive therapy initiation (whichever occurs first)
Time frame: 24 hours prior to discharge through discharge, up to 7 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lasix (Furosemide) | Mean Arterial Blood Pressure (MAP) | 88.9 mmHg | Standard Deviation 7.4 |
| Placebo | Mean Arterial Blood Pressure (MAP) | 86.8 mmHg | Standard Deviation 7.1 |
Secondary
Breastfeeding Continuation Rate
Number of participants continuing to breastfeed of those who initiated breastfeeding after delivery. This outcome was assessed at Discharge (up to 7 days), 2 weeks postpartum, and 6 weeks postpartum. Data is reported at 2 weeks and 6 weeks postpartum.
Time frame: 2 weeks postpartum, 6 weeks postpartum
Population: 1 participant in the Placebo Arm (who completed Primary Outcome) withdrew from the study before the Secondary Outcome data was collected.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lasix (Furosemide) | Breastfeeding Continuation Rate | 2 weeks | 5 Participants |
| Lasix (Furosemide) | Breastfeeding Continuation Rate | 6 weeks | 7 Participants |
| Placebo | Breastfeeding Continuation Rate | 2 weeks | 5 Participants |
| Placebo | Breastfeeding Continuation Rate | 6 weeks | 5 Participants |
Secondary
Percent of Recorded Blood Pressures That Are Elevated
Percent of recorded blood pressures that are elevated (\>140 systolic OR \>90 diastolic).
Time frame: Discharge (up to 7 days), 2 weeks postpartum, 6 weeks postpartum
Population: 1 participant in the Placebo Arm withdrew from the study before the Secondary Outcome data was collected.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Lasix (Furosemide) | Percent of Recorded Blood Pressures That Are Elevated | Discharge | 4 percent |
| Lasix (Furosemide) | Percent of Recorded Blood Pressures That Are Elevated | 2 weeks postpartum | 8 percent |
| Lasix (Furosemide) | Percent of Recorded Blood Pressures That Are Elevated | 6 weeks postpartum | 8 percent |
| Placebo | Percent of Recorded Blood Pressures That Are Elevated | Discharge | 0 percent |
| Placebo | Percent of Recorded Blood Pressures That Are Elevated | 2 weeks postpartum | 5 percent |
| Placebo | Percent of Recorded Blood Pressures That Are Elevated | 6 weeks postpartum | 5 percent |
Secondary
Rate of de Novo Postpartum Preeclampsia
Number of participants who develop de novo postpartum hypertension. This outcome was assessed at Discharge (up to 7 days), 2 weeks postpartum, and 6 weeks postpartum. Data is reported at 6 weeks postpartum.
Time frame: Discharge (up to 7 days), 2 weeks postpartum, 6 weeks postpartum
Population: 1 participant in the Placebo Arm (who completed Primary Outcome) withdrew from the study before the Secondary Outcome data was collected.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lasix (Furosemide) | Rate of de Novo Postpartum Preeclampsia | 5 Participants |
| Placebo | Rate of de Novo Postpartum Preeclampsia | 3 Participants |
Secondary
Rate of Initiation of Antihypertensives
Number of participants receiving intravenous antihypertensive therapy and initiated on oral hypertensive therapy. This outcome was assessed at Discharge (up to 7 days), 2 weeks postpartum, and 6 weeks postpartum. Data is reported at 6 weeks postpartum.
Time frame: Discharge (up to 7 days), 2 weeks postpartum, 6 weeks postpartum
Population: 1 participant in the Placebo Arm (who completed Primary Outcome) withdrew from the study before the Secondary Outcome data was collected.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lasix (Furosemide) | Rate of Initiation of Antihypertensives | 4 Participants |
| Placebo | Rate of Initiation of Antihypertensives | 3 Participants |
Secondary
Rate of Magnesium Sulfate Administration
Number of participants who receive intravenous magnesium sulfate for seizure prophylaxis. This outcome was assessed at Discharge (up to 7 days), 2 weeks postpartum, and 6 weeks postpartum. Data is reported at 6 weeks postpartum.
Time frame: Discharge (up to 7 days), 2 weeks postpartum, 6 weeks postpartum
Population: 1 participant in the Placebo Arm (who completed Primary Outcome) withdrew from the study before the Secondary Outcome data was collected.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lasix (Furosemide) | Rate of Magnesium Sulfate Administration | 2 Participants |
| Placebo | Rate of Magnesium Sulfate Administration | 2 Participants |
Secondary
Rate of Severe Maternal Morbidity
Number of participants experiencing severe maternal morbidity (e.g. seizure, stroke, Posterior reversible encephalopathy syndrome (PRES), death, etc.) This outcome was assessed at Discharge (up to 7 days), 2 weeks postpartum, and 6 weeks postpartum. Data is reported at 6 weeks postpartum.
Time frame: Discharge (up to 7 days), 2 weeks postpartum, 6 weeks postpartum
Population: 1 participant in the Placebo Arm (who completed Primary Outcome) withdrew from the study before the Secondary Outcome data was collected.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lasix (Furosemide) | Rate of Severe Maternal Morbidity | 0 Participants |
| Placebo | Rate of Severe Maternal Morbidity | 1 Participants |
Secondary
Rate of Triage or Emergency Department (ED) Presentation/Readmission
Number of participants who experienced triage or ED presentation/readmission for hypertensive-related complaints. This outcome was assessed at 2 weeks postpartum and 6 weeks postpartum. Data is reported at 6 weeks postpartum.
Time frame: 2 weeks postpartum, 6 weeks postpartum
Population: 1 participant in the Placebo Arm (who completed Primary Outcome) withdrew from the study before the Secondary Outcome data was collected.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lasix (Furosemide) | Rate of Triage or Emergency Department (ED) Presentation/Readmission | 4 Participants |
| Placebo | Rate of Triage or Emergency Department (ED) Presentation/Readmission | 2 Participants |
Secondary
Time to Discharge
Time until discharge from the hospital
Time frame: Randomization through discharge, up to 7 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Lasix (Furosemide) | Time to Discharge | 2.0 days |
| Placebo | Time to Discharge | 2.0 days |