TROPHY: ToRsemide for pOstpartum HYpertension

• Sponsor: The University of Texas Health Science Center, Houston (Other)
• Overall Status: Completed
• CT.gov ID: NCT02813551
• Collaborator: (none)
• Enrollment: 118
• Location: 1
• Arms: 2
• Duration (Months): 13.3
• Patients Per Site Per Month: 8.9

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Preeclampsia	Drug: Torsemide; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 118 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Torsemide for the Prevention of Persistent Postpartum Hypertension in Preeclamptic Women: A Randomized, Placebo-Control Trial
• Study Start Date: Aug 1, 2016
• Actual Primary Completion Date: Jul 28, 2017
• Actual Study Completion Date: Sep 9, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Torsemide Torsemide 20 mg daily for 5 days	Drug: Torsemide; Other Names: Demadex, torasemide
Placebo Comparator: Placebo Placebo 20 mg daily for 5 days	Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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]

2. Number of Participants Requiring Postpartum Readmission [0-6 weeks after delivery]

3. Length of Hospital Stay After Delivery [0-5 days after delivery]

4. Weight Change [at the time of randomization (within 24 hours of delivery); at discharge (about 1-5 days after delivery)]

5. 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.

6. Number of Participants With Persistent Postpartum Hypertension (Systolic Blood Pressure ≥140 and/or Diastolic Blood Pressure ≥ 90 mmHg) [7-10 days after delivery]

7. Number of Participants With Persistent Postpartum Hypertension (Systolic Blood Pressure ≥140 and/or Diastolic Blood Pressure ≥ 90 mmHg) [6 weeks after delivery]

8. Number of Participants With Side Effects of Therapy - Hypokalemia (Low Blood Potassium Levels) [0-5 days after delivery]

9. Number of Participants With Side Effects of Therapy - Decreased Breast Milk [0-5 days after delivery]

10. 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.

Other Outcome Measures

1. Torsemide Concentrations in Breast Milk [0-5 days after delivery]

   Ancillary study

2. Electrolyte Profile in Maternal Serum [0-5 days after delivery]

   Concentrations of: Sodium, Potassium, Calcium

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The University of Texas Health Science Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• The University of Texas Health Science Center, Houston

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 23, 2016

More Information

Publications

None provided.

• Responsible Party: Oscar Andres Viteri Molina, Maternal-Fetal Medicine Fellow, The University of Texas Health Science Center, Houston
• ClinicalTrials.gov Identifier: NCT02813551
• Other Study ID Numbers: HSC-MS-16-0198
• First Posted: Jun 27, 2016
• Last Update Posted: Apr 10, 2019
• Last Verified: Mar 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Keywords provided by Oscar Andres Viteri Molina, Maternal-Fetal Medicine Fellow, The University of Texas Health Science Center, Houston: Preeclampsia, puerperium
• Additional relevant MeSH terms: Pre-Eclampsia; Hypertension; Torsemide

Study Results

Participant Flow

Arm/Group Title	Torsemide	Placebo
Arm/Group Description	Torsemide 20 mg daily for 5 days	Placebo 20 mg daily for 5 days
Period Title: Overall Study
STARTED	59	59
COMPLETED	58	57
NOT COMPLETED	1	2

Baseline Characteristics

Arm/Group Title	Torsemide	Placebo	Total
Arm/Group Description	Torsemide 20 mg daily for 5 days	Placebo 20 mg daily for 5 days	Total of all reporting groups
Overall Participants	59	59	118
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	26.9 (6.1)	28.2 (6.8)	27.6 (6.5)
Sex: Female, Male (Count of Participants)
Female	59 100%	59 100%	118 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	16 27.1%	13 22%	29 24.6%
Not Hispanic or Latino	43 72.9%	46 78%	89 75.4%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
Black or African American	33 55.9%	35 59.3%	68 57.6%
Caucasian	9 15.3%	11 18.6%	20 16.9%
Hispanic	16 27.1%	13 22%	29 24.6%
Other	1 1.7%	0 0%	1 0.8%
Region of Enrollment (Count of Participants)
United States	59 100%	59 100%	118 100%
Body Mass Index (BMI) at delivery (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	38.3 (10.4)	37.0 (9.9)	37.7 (10.2)
Married (Count of Participants)
Count of Participants [Participants]	21 35.6%	20 33.9%	41 34.7%
Nulliparous (Count of Participants)
Count of Participants [Participants]	38 64.4%	31 52.5%	69 58.5%
Smoker (Count of Participants)
Count of Participants [Participants]	1 1.7%	5 8.5%	6 5.1%
Use of illicit drugs (Count of Participants)
Count of Participants [Participants]	6 10.2%	5 8.5%	11 9.3%
Use of Cocaine (Count of Participants)
Count of Participants [Participants]	1 1.7%	0 0%	1 0.8%
Prenatal care (Count of Participants)
Count of Participants [Participants]	59 100%	55 93.2%	114 96.6%
Form of Payment (Count of Participants)
Government/Subsidized Insurance	46 78%	44 74.6%	90 76.3%
Private Insurance	12 20.3%	14 23.7%	26 22%
None/Self Paid	1 1.7%	1 1.7%	2 1.7%
Pregestational Diabetes (Count of Participants)
Count of Participants [Participants]	7 11.9%	6 10.2%	13 11%
Gestational Diabetes (Count of Participants)
Count of Participants [Participants]	5 8.5%	5 8.5%	10 8.5%
Chronic Hypertension (Count of Participants)
Count of Participants [Participants]	15 25.4%	15 25.4%	30 25.4%
Asthma (Count of Participants)
Count of Participants [Participants]	4 6.8%	12 20.3%	16 13.6%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Persistent Postpartum Hypertension Defined as Systolic Blood Pressure ≥ 150 and/or Diastolic Blood Pressure ≥ 100 mmHg
Description	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

Outcome Measure Data

Analysis Population Description

Intention-to-treat

Arm/Group Title	Torsemide	Placebo
Arm/Group Description	Torsemide 20 mg daily for 5 days	Placebo 20 mg daily for 5 days
Measure Participants	59	59
Count of Participants [Participants]	26 44.1%	34 57.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Torsemide, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.76
	Confidence Interval	(2-Sided) 95%; 0.53 to 1.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

Intention-to-treat

Arm/Group Title	Torsemide	Placebo
Arm/Group Description	Torsemide 20 mg daily for 5 days	Placebo 20 mg daily for 5 days
Measure Participants	59	59
Count of Participants [Participants]	7 11.9%	6 10.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Torsemide, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.2
	Confidence Interval	(2-Sided) 95%; 0.4 to 3.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Number of Participants Requiring Postpartum Readmission
Time Frame	0-6 weeks after delivery

Outcome Measure Data

Analysis Population Description

Intention-to-treat

Arm/Group Title	Torsemide	Placebo
Arm/Group Description	Torsemide 20 mg daily for 5 days	Placebo 20 mg daily for 5 days
Measure Participants	59	59
Count of Participants [Participants]	3 5.1%	1 1.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Torsemide, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	3.0
	Confidence Interval	(2-Sided) 95%; 0.3 to 28
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Length of Hospital Stay After Delivery
Time Frame	0-5 days after delivery

Outcome Measure Data

Analysis Population Description

Intention-to-treat

Arm/Group Title	Torsemide	Placebo
Arm/Group Description	Torsemide 20 mg daily for 5 days	Placebo 20 mg daily for 5 days
Measure Participants	59	59
Median (Inter-Quartile Range) [hours]	68	54

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Torsemide, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.1
	Confidence Interval	(2-Sided) 95%; 1.0 to 1.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Weight Change
Time Frame	at the time of randomization (within 24 hours of delivery); at discharge (about 1-5 days after delivery)

Outcome Measure Data

Analysis Population Description

Intention-to-treat

Arm/Group Title	Torsemide	Placebo
Arm/Group Description	Torsemide 20 mg daily for 5 days	Placebo 20 mg daily for 5 days
Measure Participants	59	59
Mean (Standard Deviation) [pounds]	3.01 (3.85)	2.08 (2.69)

6. Secondary Outcome

Title	Change in Lower Extremity Edema
Description	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)

Outcome Measure Data

Analysis Population Description

Intention-to-treat

Arm/Group Title	Torsemide	Placebo
Arm/Group Description	Torsemide 20 mg daily for 5 days	Placebo 20 mg daily for 5 days
Measure Participants	59	59
Mean (Standard Deviation) [millimeters]	-1.29 (12.08)	-2.9 (14.08)

7. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Torsemide	Placebo
Arm/Group Description	Torsemide 20 mg daily for 5 days	Placebo 20 mg daily for 5 days
Measure Participants	21	28
Count of Participants [Participants]	9 15.3%	11 18.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Torsemide, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.1
	Confidence Interval	(2-Sided) 95%; 1.0 to 1.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Number of Participants With Persistent Postpartum Hypertension (Systolic Blood Pressure ≥140 and/or Diastolic Blood Pressure ≥ 90 mmHg)
Time Frame	6 weeks after delivery

Outcome Measure Data

Analysis Population Description

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/Group Title	Torsemide	Placebo
Arm/Group Description	Torsemide 20 mg daily for 5 days	Placebo 20 mg daily for 5 days
Measure Participants	23	31
Count of Participants [Participants]	8 13.6%	11 18.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Torsemide, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.0
	Confidence Interval	(2-Sided) 95%; 0.5 to 1.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Number of Participants With Side Effects of Therapy - Hypokalemia (Low Blood Potassium Levels)
Time Frame	0-5 days after delivery

Outcome Measure Data

Analysis Population Description

Blood potassium levels were only collected for 22 in the torsemide group and 31 in the placebo group.

Arm/Group Title	Torsemide	Placebo
Arm/Group Description	Torsemide 20 mg daily for 5 days	Placebo 20 mg daily for 5 days
Measure Participants	22	31
Count of Participants [Participants]	1 1.7%	4 6.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Torsemide, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.4
	Confidence Interval	(2-Sided) 95%; 0.1 to 2.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Number of Participants With Side Effects of Therapy - Decreased Breast Milk
Time Frame	0-5 days after delivery

Outcome Measure Data

Analysis Population Description

Intention-to-treat

Arm/Group Title	Torsemide	Placebo
Arm/Group Description	Torsemide 20 mg daily for 5 days	Placebo 20 mg daily for 5 days
Measure Participants	59	59
Count of Participants [Participants]	1 1.7%	0 0%

11. Secondary Outcome

Title	Number of Participants With Severe Composite Maternal Morbidity
Description	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

Outcome Measure Data

Analysis Population Description

Intention-to-treat

Arm/Group Title	Torsemide	Placebo
Arm/Group Description	Torsemide 20 mg daily for 5 days	Placebo 20 mg daily for 5 days
Measure Participants	59	59
Count of Participants [Participants]	0 0%	0 0%

12. Other Pre-specified Outcome

Title	Torsemide Concentrations in Breast Milk
Description	Ancillary study
Time Frame	0-5 days after delivery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

13. Other Pre-specified Outcome

Title	Electrolyte Profile in Maternal Serum
Description	Concentrations of: Sodium, Potassium, Calcium
Time Frame	0-5 days after delivery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	6 weeks
Adverse Event Reporting Description	Only related adverse events were recorded. Blood potassium levels were only collected for 22 in the torsemide group and 31 in the placebo group, thus only 22 in the torsemide group and 31 in the placebo group are indicated as at risk for hypokalemia.
Arm/Group Title	Torsemide		Placebo
Arm/Group Description	Torsemide 20 mg daily for 5 days		Placebo 20 mg daily for 5 days
All Cause Mortality
	Torsemide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/59 (0%)		0/59 (0%)
Serious Adverse Events
	Torsemide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/59 (0%)		0/59 (0%)
Other (Not Including Serious) Adverse Events
	Torsemide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/59 (3.4%)		4/59 (6.8%)
General disorders
Hypokalemia (low blood potassium levels)	1/22 (4.5%)	1	4/31 (12.9%)	4
Pregnancy, puerperium and perinatal conditions
Decreased breast milk	1/59 (1.7%)	1	0/59 (0%)	0

Limitations/Caveats

Median hospital stay <3 days, but sample size powered to detect differences in up to 5 days. High rate of clinic no-shows. Not powered to detect differences in secondary outcomes. Edema measurements done with stocking, which may affect reliability.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.