Clinical trial NCT02623036: The Use of Ambulatory Blood Pressure Monitors to Assess Angiotensin Converting Enzyme Inhibitors
Official title: The Use of Ambulatory Blood Pressure Monitors to Assess Angiotensin Converting Enzyme Inhibitors in Resistant Hypertension
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Hypertension, Resistant to Conventional Therapy
Keywords: chronotherapy
angiotensin converting enzyme inhibitors
ambulatory blood pressure monitoring
Lead sponsor: Memorial Health University Medical Center
Sponsor class: OTHER
First posted: 2015-12-07
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline nighttime blood pressure
timeFrame: Baseline and 4-6 weeks
Secondary outcomes:
measure: Change from baseline night to day blood pressure ratio (dipping status)
timeFrame: Baseline and 4-6 weeks
measure: Change from baseline 24 Hour Blood Pressure
timeFrame: Baseline and 4-6 weeks
Other outcomes:
Locations:
city: Savannah
country: United States
facility: Memorial Family Medicine Center
state: Georgia
Study officials:
affiliation: Memorial Health University Medical Center
name: John D. Bucheit, Pharm D
role: PRINCIPAL_INVESTIGATOR
References:
citation: Calhoun DA, Jones D, Textor S, Goff DC, Murphy TP, Toto RD, White A, Cushman WC, White W, Sica D, Ferdinand K, Giles TD, Falkner B, Carey RM; American Heart Association Professional Education Committee. Resistant hypertension: diagnosis, evaluation, and treatment: a scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Circulation. 2008 Jun 24;117(25):e510-26. doi: 10.1161/CIRCULATIONAHA.108.189141.
citation: Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Bohm M, Christiaens T, Cifkova R, De Backer G, Dominiczak A, Galderisi M, Grobbee DE, Jaarsma T, Kirchhof P, Kjeldsen SE, Laurent S, Manolis AJ, Nilsson PM, Ruilope LM, Schmieder RE, Sirnes PA, Sleight P, Viigimaa M, Waeber B, Zannad F; Task Force Members. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2013 Jul;31(7):1281-357. doi: 10.1097/01.hjh.0000431740.32696.cc. No abstract available.
citation: Weisser K, Schloos J, Lehmann K, Dusing R, Vetter H, Mutschler E. Pharmacokinetics and converting enzyme inhibition after morning and evening administration of oral enalapril to healthy subjects. Eur J Clin Pharmacol. 1991;40(1):95-9. doi: 10.1007/BF00315146.