Oral Combined Hydrochlorothiazide/Lisinopril Versus Oral Nifedipine for Postpartum Hypertension

Oral Combined Hydrochlorothiazide/Lisinopril Versus Oral Nifedipine for Postpartum Hypertension: A Comparative Effectiveness Pilot Randomized Controlled Trial

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05049616

Acronym

ACE

Enrollment

Registered

2021-09-20

Start date

2021-10-18

Completion date

2023-09-01

Last updated

2025-11-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Hypertension in Pregnancy, Postpartum Preeclampsia

Brief summary

The purpose of this study is to see if a combined pill of Angiotensin-converting enzyme (ACE) inhibitors (a medication that helps relax your veins and arteries to lower your blood pressure) with diuretics (sometimes called water pills, help rid your body of salt and water) will control blood pressure better than a different blood pressure medication of calcium channel blocker (lower your blood pressure by preventing calcium from entering the cells of your heart and arteries). Both medications are part of our usual care for high blood pressure after delivery.

Detailed description

In individuals with preeclampsia, persistent hypertension and edema result in part from the mobilization of up to 8 liters of fluid and sodium from the extravascular to intravascular space. The increased urinary sodium excretion on days 3-5 postpartum likely results from higher atrial natriuretic peptide concentrations in plasma and activation of the renin-angiotensin-aldosterone system. Adding diuretics for postpartum hypertension has been associated with better blood pressure control in some of the studies. * CVD is the leading cause for mortality worldwide. * Primary prevention is more effective than treating CVD. * Pregnancy is often the 1st adult engagement with the healthcare system. * Preeclampsia is a risk factor for long term CVD, even after controlling for mutual risk factors. * CVD is the leading cause for pregnancy related mortality. * There is no good data regarding the optimal medications to control blood pressure after delivery. * ACE inhibitors play an important role in controlling blood pressure outside of pregnancy and there is extensive evidence to support their cardioprotective effects. * The optimal use of diuretics in the postpartum in patients with preeclampsia, require further study and clarification to augment current management schemes. Hypothesis: that in postpartum women with hypertensive disorders, oral combined Hydrochlorothiazide/Lisinopril will reduce postpartum hypertension at 7 days after delivery compared to usual care with calcium channel blockers.

Interventions

DRUGACE Inhibitors and Diuretics

Hctz/Lisinopril (brand name: Zestoretic)

DRUGNIFEdipine ER

Extended release nifedipine

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Intervention model description

randomized control trial

Eligibility

Sex/Gender

FEMALE

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Postpartum women at ≥ 18 years of age * Postpartum diagnosis of persistent hypertension (2 measurements of Systolic BP ≥150 and/or diastolic BP ≥ 100 or systolic BP ≥140 and/or diastolic BP ≥ 90 for people with diabetes) requiring an oral medication based on the ACOG criteria or * Hypertensive disorder of pregnancy diagnosed antepartum or intrapartum requiring blood pressure medication in the postpartum * Chronic hypertension requiring blood pressure medication postpartum

Exclusion criteria

* Urine output \< 30 cc/h prior to screening for eligibility * Creatinine \> 1.4 during current admission * End-stage renal disease * Hypersensitivity to ACE inhibitors or sulfa drugs * Idiopathic/hereditary angioedema * Hyperkalemia (serum potassium \>5 mEq/L) during current admission * Pulmonary edema

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Stage 2 Hypertension	7-10 after delivery	Stage 2 hypertension at day 7-10 after delivery (defined as SBP ≥ 140 and/or DBP ≥ 90 mmHg) or admission to the hospital for blood pressure control prior to day 10. Primary outcome will be calculated as the average BP reading for day 7-10 after delivery.

Secondary

Measure	Time frame	Description
Number of Participants Who Received Additional Antihypertensive During Admission	7-10 days postpartum	number of participants who received additional antihypertensive during admission, at 7-10 days postpartum.
Postpartum Length of Stay	up to 30 days after delivery	time spent in hospital following delivery
Postpartum Readmission	up to 30 days after delivery	occurrence of returning to hospital for admission postpartum
Time to Blood Pressure Control	10 days	The time from delivery to Blood Pressure control (i.e time from delivery to last BP \<150/100).
Incidence of Persistent Postpartum Hypertension	6 weeks postpartum	Incidence of persistent postpartum hypertension 6 weeks postpartum (SBP ≥ 140 and/or DBP ≥ 90 mmHg).
Occurrence of Proteinuria	7-10 days, and 6 weeks postpartum	Proteinuria is measured by urine protein creatinine ratio
Presense of Labs Abnormality	7-10 days, and 6 weeks postpartum	Labs abnormality including hyperkalemia or creatinine increase
Compliance With Medications	at the time of the 1st postpartum clinic visit, which is about 6 to 37 days after birth	Compliance with medications. The patient will be asked to bring their medication bottle with them and the compliance will be measured by counting pills at each postpartum visit.
Time to Control Blood Pressure	3 month-1 year	Blood pressure at 3 month, 6 month, 9 month, 1 year after delivery and need for BP medications. Definition of controlled blood pressure is (SBP \< 140 and/or DBP \< 90 mmHg). This will be assessed by telephone encounter with the patient
Number of Participants With Severe Postpartum Hypertension	7-10 after delivery	severe postpartum hypertension (SBP≥160 and/or DBP≥110 mmHg on 2 occasions, 15 minutes apart)
Postpartum Complications- Number of Participants With ICU Admission	10 days postpartum	Need for ICU admission
Postpartum Complications- Number of Participants With HELLP (Hemolysis, Elevated Liver Enzymes and Low Platelets) Syndrome	10 days postpartum	Hemolysis, elevated liver enzymes, low platelet count: HELLP
Postpartum Complications- Number of Participants With Eclampsia	10 days postpartum	Eclampsia, which is considered a complication of severe preeclampsia, is commonly defined as new onset of grand mal seizure activity and/or unexplained coma during pregnancy or postpartum in a woman with signs or symptoms of preeclampsia.
Postpartum Complications- Number of Participants With Stroke	10 days postpartum	Stroke
Postpartum Complications- Number of Participants With Renal Failure	10 days postpartum	Renal failure
Postpartum Complications- Number of Participants With Pulmonary Edema	10 days postpartum	Pulmonary edema
Postpartum Complications - Number of Participants With Cardiomyopathy	10 days postpartum	Cardiomyopathy
Postpartum Complications- Number of Participants With Maternal Death	10 days postpartum	Maternal death
Receipt of Additional Antihypertensive During Admission	6 weeks postpartum	Receipt of additional antihypertensive during admission at 6 weeks postpartum
Number of Patients Receiving Primary Care With BP Measurement	1 year postpartum	Number of patients receiving primary care with BP measurement at 1 year

Countries

United States

Participant flow

Participants by arm

Arm	Count
Hctz/Lisinopril Hctz/Lisinopril for postpartum management of hypertension. either a combined pill of ACE inhibitors and diuretics (Hydrochlorothiazide/Lisinopril) ACE Inhibitors and Diuretics: Hctz/Lisinopril (brand name: Zestoretic)	31
Extended release nifedipine calcium channel blocker (Nifedipine NIFEdipine ER: Extended release nifedipine	36
Total	67

Baseline characteristics

Characteristic	Hctz/Lisinopril	Extended release nifedipine	Total
Age, Customized <35 years	24 Participants	20 Participants	44 Participants
Age, Customized >=35 years	7 Participants	16 Participants	23 Participants
Gestational weeks at delivery	34.4 weeks	36.6 weeks	35.4 weeks
Number of Cesarean delivery	23 Participants	20 Participants	43 Participants
Number of participants that are Married/living with partner	11 Participants	14 Participants	25 Participants
Number of participants who had labor induced	9 Participants	18 Participants	27 Participants
Number of participants who Need IV Blood Pressure medications prior to randomization	11 Participants	11 Participants	22 Participants
Number of participants who Smoke during pregnancy	1 Participants	4 Participants	5 Participants
Number of participants who Use Blood Pressure medication during pregnancy	15 Participants	13 Participants	28 Participants
Number of participants with a BMI ≥ 30	20 Participants	25 Participants	45 Participants
Number of participants with Alcohol use during pregnancy	0 Participants	1 Participants	1 Participants
Number of participants with Chronic hypertension	14 Participants	15 Participants	29 Participants
Number of participants with Diabetes diagnosed prior to pregnancy	6 Participants	7 Participants	13 Participants
Number of participants with Gestational diabetes	2 Participants	5 Participants	7 Participants
Number of participants with Hypertensive disorder during pregnancy	28 Participants	31 Participants	59 Participants
Number of participants with New onset postpartum hypertension	0 Participants	5 Participants	5 Participants
Number of participants with Nulliparous	4 Participants	7 Participants	11 Participants
Number of participants with Preeclampsia with severe features	24 Participants	27 Participants	51 Participants
Number of participants with private insurance for prenatal care	7 Participants	18 Participants	25 Participants
Number of participants with Substance use during pregnancy	1 Participants	5 Participants	6 Participants
Number of participants with Thyroid disease	1 Participants	3 Participants	4 Participants
Number of pre-term delivery	25 Participants	20 Participants	45 Participants
Postpartum day at randomization	1.4 days	1.0 days	1.2 days
Pre-pregnancy Body Mass Index	40.1 kg/m^2	37.8 kg/m^2	38.5 kg/m^2
Race/Ethnicity, Customized Asian	3 Participants	1 Participants	4 Participants
Race/Ethnicity, Customized Hispanic	9 Participants	7 Participants	16 Participants
Race/Ethnicity, Customized Non-Hispanic Black	16 Participants	24 Participants	40 Participants
Race/Ethnicity, Customized Non-Hispanic White	3 Participants	4 Participants	7 Participants
Region of Enrollment United States	31 participants	36 participants	67 participants
Sex: Female, Male Female	31 Participants	36 Participants	67 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 / 34	0 / 36
other Total, other adverse events	0 / 34	0 / 36
serious Total, serious adverse events	2 / 34	0 / 36

Outcome results

Primary

Number of Participants With Stage 2 Hypertension

Stage 2 hypertension at day 7-10 after delivery (defined as SBP ≥ 140 and/or DBP ≥ 90 mmHg) or admission to the hospital for blood pressure control prior to day 10. Primary outcome will be calculated as the average BP reading for day 7-10 after delivery.

Time frame: 7-10 after delivery

Population: Data were not collected for 1 participants in the Hctz/Lisionpril arm. Data were not collected for 8 participants in the extended release nifedipine arm.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Hctz/Lisinopril	Number of Participants With Stage 2 Hypertension	8 Participants
Extended release nifedipine	Number of Participants With Stage 2 Hypertension	12 Participants

Secondary

Compliance With Medications

Compliance with medications. The patient will be asked to bring their medication bottle with them and the compliance will be measured by counting pills at each postpartum visit.

Time frame: at the time of the 1st postpartum clinic visit, which is about 6 to 37 days after birth

Population: Data were not collected for 4 participants in the Hctz/Lisinopril arm. Data were not collected for 8 participants in the Extended release nifedipine arm

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Hctz/Lisinopril	Compliance With Medications	22 Participants
Extended release nifedipine	Compliance With Medications	26 Participants

Secondary

Incidence of Persistent Postpartum Hypertension

Incidence of persistent postpartum hypertension 6 weeks postpartum (SBP ≥ 140 and/or DBP ≥ 90 mmHg).

Time frame: 6 weeks postpartum

Population: Data were not collected for this outcome measure.

Secondary

Number of Participants Who Received Additional Antihypertensive During Admission

number of participants who received additional antihypertensive during admission, at 7-10 days postpartum.

Time frame: 7-10 days postpartum

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Hctz/Lisinopril	Number of Participants Who Received Additional Antihypertensive During Admission	6 Participants
Extended release nifedipine	Number of Participants Who Received Additional Antihypertensive During Admission	5 Participants

Secondary

Number of Participants With Severe Postpartum Hypertension

severe postpartum hypertension (SBP≥160 and/or DBP≥110 mmHg on 2 occasions, 15 minutes apart)

Time frame: 7-10 after delivery

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Hctz/Lisinopril	Number of Participants With Severe Postpartum Hypertension	6 Participants
Extended release nifedipine	Number of Participants With Severe Postpartum Hypertension	5 Participants

Secondary

Number of Patients Receiving Primary Care With BP Measurement

Number of patients receiving primary care with BP measurement at 1 year

Time frame: 1 year postpartum

Population: Data were not collected for this outcome because participants were lost to follow up.

Secondary

Occurrence of Proteinuria

Proteinuria is measured by urine protein creatinine ratio

Time frame: 7-10 days, and 6 weeks postpartum

Population: Data were not collected for this outcome measure

Secondary