The Use of Ambulatory Blood Pressure Monitors to Assess Angiotensin Converting Enzyme Inhibitors

Study Overview
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Brief Summary
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The purpose of this study is to use ambulatory blood pressure monitors to investigate whether enalapril is superior to lisinopril in managing nocturnal hypertension in patients with resistant hypertension currently treated with daytime angiotensin converting enzyme inhibitors.

Detailed Description
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Resistant hypertension is defined as blood pressure > 140/90 mm Hg while adherent to three or more antihypertensive medications or < 140/90 mm Hg treated with four or more antihypertensives. Patients with resistant hypertension may be at risk for elevated nighttime blood pressure >120/70 mm Hg and non-dipping (night/day blood pressure > 0.9). A higher rate of cardiovascular events occur during the morning surge partially attributed elevated nighttime blood pressure due to increased renin angiotensin aldosterone system (RAAS) activity. Angiotensin converting enzyme inhibitors (ACEIs) suppress RAAS activity This prospective randomized parallel-group pilot study will occur at Memorial Family Medicine. Eligible patients will undergo three study visits over a 5-8 week span. After providing written informed consent, patients will complete an initial screening visit assessing 25 hour blood pressure using ambulatory blood pressure monitors. Patients will continue the study if they are found to have a nighttime blood pressure >120/70 mm Hg. Patients continuing the study will be randomly assigned to equivalent dose lisinopril or enalapril treatment arms and their administration time will be changed to bedtime. At the final visit, patients will complete a final ambulatory blood pressure analysis to reassess nighttime blood pressure and dipping status. It's expected that patients with enalapril treatment will have superior nighttime blood pressure reduction compared to the lisinopril treatment group. If the expected outcome occurs, more patients in the enalapril group will meet their nighttime blood pressure goal (<120/70 mm Hg) and exhibit a dipping pattern. Current evidence suggests that patients with normal nighttime blood pressure and dipping pattern are at a lower risk for cardiovascular morbidity and mortality.

Official Title
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The Use of Ambulatory Blood Pressure Monitors to Assess Angiotensin Converting Enzyme Inhibitors in Resistant Hypertension

Conditions
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Hypertension, Resistant to Conventional Therapy

Intervention / Treatment
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* Drug: Equivalent dose enalapril
* Drug: Equivalent dose lisinopril


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with clinic blood pressure > 140/90 mm Hg on 3 antihypertensives or clinic blood pressure < 140/90 mm Hg on 4 antihypertensives Currently treated with an angiotensin converting enzyme inhibitor Exclusion Criteria: Chronic kidney disease (CKD) stage 4 or worse Pheochromocytoma Unstable cardiovascular disease Stroke, Transient Ischemic Attack, Unstable Angina, or Myocardial infarction in the last 30 days Hyperaldosteronism Current pregnancy Shift worker at night Presenting blood pressure > 180/110 mm Hg

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Enalapril arm<br>Patients randomized to this group will receive equivalent dose enalapril to their current ACEI therapy and change the administration time to bedtime. | Drug: Equivalent dose enalapril<br>* Chronotherapy with enalapril.<br>* Other names: Vasotec;|
| Active Comparator: Lisinopril arm<br>Patients randomized to this group will receive equivalent dose lisinopril to their current ACEI therapy and change the administration time to bedtime. | Drug: Equivalent dose lisinopril<br>* Chronotherapy with lisinopril<br>* Other names: Prinivil;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline nighttime blood pressure | Average blood pressure between 0000-0600. | Baseline and 4-6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline night to day blood pressure ratio (dipping status) | Nighttime blood pressure (average 0000-0600)/Daytime blood pressure 0900-2100. This outcomes evaluates patients' circadian blood pressure pattern. A normal circadian blood pressure pattern shows a 10% decrease in both systolic and diastolic blood pressure at night. This will help measure the impact of chronotherapy between the 2 study agents. | Baseline and 4-6 weeks | 
| Change from baseline 24 Hour Blood Pressure | Average blood pressure over 24 hours (0000-2359) | Baseline and 4-6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chronotherapy, angiotensin converting enzyme inhibitors, ambulatory blood pressure monitoring