Oral Combined Hydrochlorothiazide/Lisinopril Versus Oral Nifedipine for Postpartum Hypertension (ACE)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Hypertension in Pregnancy; Postpartum Preeclampsia
• Intervention / Treatment: Drug: ACE Inhibitors and Diuretics; Drug: NIFEdipine ER

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.

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hctz/Lisinopril; Hctz/Lisinopril for postpartum management of hypertension. either a combined pill of ACE inhibitors and diuretics (Hydrochlorothiazide/Lisinopril)	Drug: ACE Inhibitors and Diuretics; Hctz/Lisinopril (brand name: Zestoretic)
Active Comparator: Extended release nifedipine; calcium channel blocker (Nifedipine	Drug: NIFEdipine ER; Extended release nifedipine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	7-10 after delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of Proteinuria	Proteinuria is measured by urine protein creatinine ratio	7-10 days, and 6 weeks postpartum
Number of Participants With Severe Postpartum Hypertension	severe postpartum hypertension (SBP≥160 and/or DBP≥110 mmHg on 2 occasions, 15 minutes apart)	7-10 after delivery
Number of Participants Who Received Additional Antihypertensive During Admission	number of participants who received additional antihypertensive during admission, at 7-10 days postpartum.	7-10 days postpartum
Postpartum Length of Stay	time spent in hospital following delivery	up to 30 days after delivery
Postpartum Readmission	occurrence of returning to hospital for admission postpartum	up to 30 days after delivery
Time to Blood Pressure Control	The time from delivery to Blood Pressure control (i.e time from delivery to last BP <150/100).	10 days
Incidence of Persistent Postpartum Hypertension	Incidence of persistent postpartum hypertension 6 weeks postpartum (SBP ≥ 140 and/or DBP ≥ 90 mmHg).	6 weeks postpartum
Presense of Labs Abnormality	Labs abnormality including hyperkalemia or creatinine increase	7-10 days, and 6 weeks postpartum
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.	at the time of the 1st postpartum clinic visit, which is about 6 to 37 days after birth
Time to Control Blood Pressure	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	3 month-1 year
Percentage of Patients Receiving Primary Care With BP Measurement	Percentage of patients receiving primary care with BP measurement at 1 year	1 year postpartum
Postpartum Complications- Number of Participants With ICU Admission	Need for ICU admission	10 days postpartum
Postpartum Complications- Number of Participants With HELLP (Hemolysis, Elevated Liver Enzymes and Low Platelets) Syndrome	Hemolysis, elevated liver enzymes, low platelet count: HELLP	10 days postpartum
Postpartum Complications- Number of Participants With Eclampsia	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.	10 days postpartum
Postpartum Complications- Number of Participants With Stroke	Stroke	10 days postpartum
Postpartum Complications- Number of Participants With Renal Failure	Renal failure	10 days postpartum
Postpartum Complications- Number of Participants With Pulmonary Edema	Pulmonary edema	10 days postpartum
Postpartum Complications - Number of Participants With Cardiomyopathy	Cardiomyopathy	10 days postpartum
Postpartum Complications- Number of Participants With Maternal Death	Maternal death	10 days postpartum
Receipt of Additional Antihypertensive During Admission	Receipt of additional antihypertensive during admission at 6 weeks postpartum	6 weeks postpartum

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center, Houston
• Investigators: Principal Investigator: Michal Fishel Bartal, MD, UT Health Science Center

Study record dates

Study Major Dates

• Study Start (Actual): October 18, 2021
• Primary Completion (Actual): June 26, 2022
• Study Completion (Estimated): October 1, 2023

Study Registration Dates

• First Submitted: August 31, 2021
• First Submitted That Met QC Criteria: September 8, 2021
• First Posted (Actual): September 20, 2021

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: July 20, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Hypertension; Pre-Eclampsia; Hypertension, Pregnancy-Induced; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Protease Inhibitors; Natriuretic Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Reproductive Control Agents; Calcium Channel Blockers; Tocolytic Agents; Nifedipine; Diuretics; Angiotensin-Converting Enzyme Inhibitors
• Other Study ID Numbers: HSC-MS-21-0476

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No