Oral Combined Hydrochlorothiazide/Lisinopril Versus Oral Nifedipine for Postpartum Hypertension

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Hypertension in Pregnancy, Postpartum Preeclampsia

Intervention / Treatment
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* Drug: ACE Inhibitors and Diuretics
* Drug: NIFEdipine ER


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: randomized control trial
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 |
| --- | --- | --- |
| 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 | 
| Occurrence of Proteinuria | Proteinuria is measured by urine protein creatinine ratio | 7-10 days, and 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 |