Preeclampsia
Conditions
Keywords
Preeclampsia, puerperium
Brief summary
Currently there is no intervention to prevent persistent postpartum hypertension in preeclamptic women. Physiologically, the use of a pharmacokinetically predictable loop-diuretic is a reasonable intervention to increase elimination of extra fluid accumulated secondary to preeclampsia.The purpose of this study is to assess if Torsemide reduces the incidence of persistent postpartum hypertension in preeclamptic women.
Interventions
DRUGTorsemide
DRUGPlacebo
Sponsors
The University of Texas Health Science Center, Houston
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Postpartum women at ≥ 18 years of age * Antepartum/intrapartum or within 24 hours postpartum diagnosis of either: * Preeclampsia * Preeclampsia with severe features * Preeclampsia superimposed to chronic hypertension
Exclusion criteria
* Chronic hypertension without superimposed preeclampsia * Gestational hypertension * Urine output \< 30 cc/h at time of randomization * Heart failure or pulmonary edema * Hypersensitivity to Torsemide or sulfonylureas * Hypokalemia (serum potassium \< 3 mEq/L) * Preexisting diuretic use within 24 hours prior to randomization
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Persistent Postpartum Hypertension Defined as Systolic Blood Pressure ≥ 150 and/or Diastolic Blood Pressure ≥ 100 mmHg | 0-5 days after delivery | Persistent postpartum hypertension was defined as sustained systolic blood pressure ≥ 150 or diastolic blood pressure ≥ 100 mmHg by postpartum day 5 or at hospital discharge, whichever occurred first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Severe Postpartum Hypertension Requiring Acute Antihypertensives (Systolic Blood Pressure ≥160 and/or Diastolic Blood Pressure ≥ 110 mmHg) | 0-6 weeks after delivery | — |
| Number of Participants Requiring Postpartum Readmission | 0-6 weeks after delivery | — |
| Length of Hospital Stay After Delivery | 0-5 days after delivery | — |
| Weight Change | at the time of randomization (within 24 hours of delivery); at discharge (about 1-5 days after delivery) | — |
| Change in Lower Extremity Edema | at the time of randomization (within 24 hours of delivery); at discharge (about 1-5 days after delivery) | Lower extremity edema was assessed by measuring right ankle circumference at 5 centimeters above the medial malleolus. |
| Number of Participants With Side Effects of Therapy - Decreased Breast Milk | 0-5 days after delivery | — |
| Number of Participants With Severe Composite Maternal Morbidity | 0-6 weeks after delivery | Severe composite maternal morbidity is defined as having any of the following: ICU admission, HELLP syndrome, eclampsia, stroke, renal failure, pulmonary edema, cardiomyopathy, or maternal death. |
| Number of Participants With Persistent Postpartum Hypertension (Systolic Blood Pressure ≥140 and/or Diastolic Blood Pressure ≥ 90 mmHg) | 7-10 days after delivery | — |
| Number of Participants With Side Effects of Therapy - Hypokalemia (Low Blood Potassium Levels) | 0-5 days after delivery | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Torsemide Concentrations in Breast Milk | 0-5 days after delivery | Ancillary study |
| Electrolyte Profile in Maternal Serum | 0-5 days after delivery | Concentrations of: Sodium, Potassium, Calcium |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Torsemide Torsemide 20 mg daily for 5 days | 59 |
| Placebo Placebo 20 mg daily for 5 days | 59 |
| Total | 118 |
Baseline characteristics
| Characteristic | Torsemide | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 26.9 years STANDARD_DEVIATION 6.1 | 28.2 years STANDARD_DEVIATION 6.8 | 27.6 years STANDARD_DEVIATION 6.5 |
| Asthma | 4 Participants | 12 Participants | 16 Participants |
| Body Mass Index (BMI) at delivery | 38.3 kg/m^2 STANDARD_DEVIATION 10.4 | 37.0 kg/m^2 STANDARD_DEVIATION 9.9 | 37.7 kg/m^2 STANDARD_DEVIATION 10.2 |
| Chronic Hypertension | 15 Participants | 15 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 16 Participants | 13 Participants | 29 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 43 Participants | 46 Participants | 89 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Form of Payment Government/Subsidized Insurance | 46 Participants | 44 Participants | 90 Participants |
| Form of Payment None/Self Paid | 1 Participants | 1 Participants | 2 Participants |
| Form of Payment Private Insurance | 12 Participants | 14 Participants | 26 Participants |
| Gestational Diabetes | 5 Participants | 5 Participants | 10 Participants |
| Married | 21 Participants | 20 Participants | 41 Participants |
| Nulliparous | 38 Participants | 31 Participants | 69 Participants |
| Pregestational Diabetes | 7 Participants | 6 Participants | 13 Participants |
| Prenatal care | 59 Participants | 55 Participants | 114 Participants |
| Race/Ethnicity, Customized Race Black or African American | 33 Participants | 35 Participants | 68 Participants |
| Race/Ethnicity, Customized Race Caucasian | 9 Participants | 11 Participants | 20 Participants |
| Race/Ethnicity, Customized Race Hispanic | 16 Participants | 13 Participants | 29 Participants |
| Race/Ethnicity, Customized Race Other | 1 Participants | 0 Participants | 1 Participants |
| Region of Enrollment United States | 59 Participants | 59 Participants | 118 Participants |
| Sex: Female, Male Female | 59 Participants | 59 Participants | 118 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Smoker | 1 Participants | 5 Participants | 6 Participants |
| Use of Cocaine | 1 Participants | 0 Participants | 1 Participants |
| Use of illicit drugs | 6 Participants | 5 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 59 | 0 / 59 |
| other Total, other adverse events | 2 / 59 | 4 / 59 |
| serious Total, serious adverse events | 0 / 59 | 0 / 59 |
Outcome results
Primary
Number of Participants With Persistent Postpartum Hypertension Defined as Systolic Blood Pressure ≥ 150 and/or Diastolic Blood Pressure ≥ 100 mmHg
Persistent postpartum hypertension was defined as sustained systolic blood pressure ≥ 150 or diastolic blood pressure ≥ 100 mmHg by postpartum day 5 or at hospital discharge, whichever occurred first.
Time frame: 0-5 days after delivery
Population: Intention-to-treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Torsemide | Number of Participants With Persistent Postpartum Hypertension Defined as Systolic Blood Pressure ≥ 150 and/or Diastolic Blood Pressure ≥ 100 mmHg | 26 Participants |
| Placebo | Number of Participants With Persistent Postpartum Hypertension Defined as Systolic Blood Pressure ≥ 150 and/or Diastolic Blood Pressure ≥ 100 mmHg | 34 Participants |
95% CI: [0.53, 1.1]
Secondary
Change in Lower Extremity Edema
Lower extremity edema was assessed by measuring right ankle circumference at 5 centimeters above the medial malleolus.
Time frame: at the time of randomization (within 24 hours of delivery); at discharge (about 1-5 days after delivery)
Population: Intention-to-treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Torsemide | Change in Lower Extremity Edema | -1.29 millimeters | Standard Deviation 12.08 |
| Placebo | Change in Lower Extremity Edema | -2.9 millimeters | Standard Deviation 14.08 |
Secondary
Length of Hospital Stay After Delivery
Time frame: 0-5 days after delivery
Population: Intention-to-treat
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Torsemide | Length of Hospital Stay After Delivery | 68 hours |
| Placebo | Length of Hospital Stay After Delivery | 54 hours |
95% CI: [1, 1.3]
Secondary
Number of Participants Requiring Postpartum Readmission
Time frame: 0-6 weeks after delivery
Population: Intention-to-treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Torsemide | Number of Participants Requiring Postpartum Readmission | 3 Participants |
| Placebo | Number of Participants Requiring Postpartum Readmission | 1 Participants |
95% CI: [0.3, 28]
Secondary
Number of Participants With Persistent Postpartum Hypertension (Systolic Blood Pressure ≥140 and/or Diastolic Blood Pressure ≥ 90 mmHg)
Time frame: 7-10 days after delivery
Population: 38 (42%) women in the torsemide group and 31 (53%) women in the placebo missed their outpatient clinic visit at 7-10 days after delivery, resulting in only 21 in the torsemide group and 28 in the placebo group being analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Torsemide | Number of Participants With Persistent Postpartum Hypertension (Systolic Blood Pressure ≥140 and/or Diastolic Blood Pressure ≥ 90 mmHg) | 9 Participants |
| Placebo | Number of Participants With Persistent Postpartum Hypertension (Systolic Blood Pressure ≥140 and/or Diastolic Blood Pressure ≥ 90 mmHg) | 11 Participants |
95% CI: [1, 1.2]
Secondary
Number of Participants With Persistent Postpartum Hypertension (Systolic Blood Pressure ≥140 and/or Diastolic Blood Pressure ≥ 90 mmHg)
Time frame: 6 weeks after delivery
Population: 36 women in the torsemide group and 28 women in the placebo group did not show to their clinic appointment 6 weeks after delivery, resulting in 23 in the torsemide group and 31 in the placebo group being analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Torsemide | Number of Participants With Persistent Postpartum Hypertension (Systolic Blood Pressure ≥140 and/or Diastolic Blood Pressure ≥ 90 mmHg) | 8 Participants |
| Placebo | Number of Participants With Persistent Postpartum Hypertension (Systolic Blood Pressure ≥140 and/or Diastolic Blood Pressure ≥ 90 mmHg) | 11 Participants |
95% CI: [0.5, 1.9]
Secondary
Number of Participants With Severe Composite Maternal Morbidity
Severe composite maternal morbidity is defined as having any of the following: ICU admission, HELLP syndrome, eclampsia, stroke, renal failure, pulmonary edema, cardiomyopathy, or maternal death.
Time frame: 0-6 weeks after delivery
Population: Intention-to-treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Torsemide | Number of Participants With Severe Composite Maternal Morbidity | 0 Participants |
| Placebo | Number of Participants With Severe Composite Maternal Morbidity | 0 Participants |
Secondary
Number of Participants With Severe Postpartum Hypertension Requiring Acute Antihypertensives (Systolic Blood Pressure ≥160 and/or Diastolic Blood Pressure ≥ 110 mmHg)
Time frame: 0-6 weeks after delivery
Population: Intention-to-treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Torsemide | Number of Participants With Severe Postpartum Hypertension Requiring Acute Antihypertensives (Systolic Blood Pressure ≥160 and/or Diastolic Blood Pressure ≥ 110 mmHg) | 7 Participants |
| Placebo | Number of Participants With Severe Postpartum Hypertension Requiring Acute Antihypertensives (Systolic Blood Pressure ≥160 and/or Diastolic Blood Pressure ≥ 110 mmHg) | 6 Participants |
95% CI: [0.4, 3.3]
Secondary
Number of Participants With Side Effects of Therapy - Decreased Breast Milk
Time frame: 0-5 days after delivery
Population: Intention-to-treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Torsemide | Number of Participants With Side Effects of Therapy - Decreased Breast Milk | 1 Participants |
| Placebo | Number of Participants With Side Effects of Therapy - Decreased Breast Milk | 0 Participants |
Secondary
Number of Participants With Side Effects of Therapy - Hypokalemia (Low Blood Potassium Levels)
Time frame: 0-5 days after delivery
Population: Blood potassium levels were only collected for 22 in the torsemide group and 31 in the placebo group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Torsemide | Number of Participants With Side Effects of Therapy - Hypokalemia (Low Blood Potassium Levels) | 1 Participants |
| Placebo | Number of Participants With Side Effects of Therapy - Hypokalemia (Low Blood Potassium Levels) | 4 Participants |
95% CI: [0.1, 2.9]
Secondary
Weight Change
Time frame: at the time of randomization (within 24 hours of delivery); at discharge (about 1-5 days after delivery)
Population: Intention-to-treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Torsemide | Weight Change | 3.01 pounds | Standard Deviation 3.85 |
| Placebo | Weight Change | 2.08 pounds | Standard Deviation 2.69 |
Other Pre-specified
Electrolyte Profile in Maternal Serum
Concentrations of: Sodium, Potassium, Calcium
Time frame: 0-5 days after delivery
Other Pre-specified
Torsemide Concentrations in Breast Milk
Ancillary study
Time frame: 0-5 days after delivery