Hypertension, Resistant to Conventional Therapy
Conditions
Keywords
chronotherapy, angiotensin converting enzyme inhibitors, ambulatory blood pressure monitoring
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.
Interventions
DRUGEquivalent dose enalapril
Chronotherapy with enalapril.
DRUGEquivalent dose lisinopril
Chronotherapy with lisinopril
Sponsors
Memorial Health University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline nighttime blood pressure | Baseline and 4-6 weeks | Average blood pressure between 0000-0600. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) |
Countries
United States
Contacts
Primary ContactJohn D Bucheit, Pharm.D.
Backup ContactCindy Gleit, M.D.
Outcome results
None listed