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

Phase 1

• Conditions: Hypertension, Resistant to Conventional Therapy
• Interventions: Drug: Equivalent dose lisinopril; Drug: Equivalent dose enalapril

• Registration Number: NCT02623036
• Lead Sponsor: Memorial Health University Medical Center

Brief Summary

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

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.

Study Timeline

• Study Start: 2015-11
• Study First Submitted: 2015-11-19
• Study First Submitted QC: 2015-12-02
• Study First Posted: 2015-12-07
• Status Verified: 2017-05
• Last Update Submitted: 2017-05-23
• Last Update Posted: 2017-05-25
• Primary Completion: 2018-04
• Study Completion: 2018-04

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 20

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Lisinopril arm	Equivalent dose lisinopril	Patients randomized to this group will receive equivalent dose lisinopril to their current ACEI therapy and change the administration time to bedtime.
Enalapril arm	Equivalent dose enalapril	Patients randomized to this group will receive equivalent dose enalapril to their current ACEI therapy and change the administration time to bedtime.

Primary Outcome Measures

Name	Time	Method
Change from baseline nighttime blood pressure	Baseline and 4-6 weeks	Average blood pressure between 0000-0600.

Secondary Outcome Measures

Name	Time	Method
Change from baseline night to day blood pressure ratio (dipping status)	Baseline and 4-6 weeks	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.
Change from baseline 24 Hour Blood Pressure	Baseline and 4-6 weeks	Average blood pressure over 24 hours (0000-2359)

Trial Locations

Locations (1)

Memorial Family Medicine Center; 🇺🇸 Savannah, Georgia, United States