Comparison of the Antihypertensive Efficacy of Valsartan and Enalapril After Missing One Dose
Information source: University of Vigo
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Hypertension
Intervention: Valsartan, Enalapril (Drug); Ambulatory blood pressure monitoring (Device); Missing one dose (Procedure)
Phase: Phase 4
Sponsored by: University of Vigo
Official(s) and/or principal investigator(s):
Ramon C Hermida, Ph.D., Principal Investigator, Affiliation: University of Vigo
This study was designed in order to evaluate the blood pressure lowering effect of valsartan
compared to enalapril over 24 hours after skipping one daily dose. Both drugs act on the
renin-angiotensin-aldosterone system (RAAS) and are widely use for the treatment of
hypertension. Previous studies had a significant limitation: the effect of a missing dose was
not evaluated after the whole 24 hours post missing dose period (48 hours after last taken
dose), and as a result, it does not imitate the real life situation of a missing dose.
Official title: Prospective, Randomized, Open-Label Study in Patients With Mild-to-Moderate Essential Hypertension to Compare the Antihypertensive Efficacy Determined by Ambulatory Blood Pressure Monitoring of Valsartan and Enalapril After Missing One Dose
Study design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Primary outcome: To demonstrate the efficacy of valsartan by testing the hypothesis of superior 24 hrs diastolic BP lowering after missing dose compared with enalapril.
To demonstrate that valsartan is more effective than enalapril in terms of systolic 24 hrs BP lowering after missing dose.
To show that valsartan is more effective than enalapril in reducing systolic and diastolic BP in the time interval 20-24 hours after dose administration.
To show that valsartan has a more favorable effect than enalapril in smoothness index and through/peak ratio.
To demonstrate that valsartan offers better safety profile than enalapril.
The incidence of cardiovascular events, such as myocardial infarction, sudden cardiac death,
ventricular arrhythmias, stroke, myocardial ischemia and angina pectoris, reaches the peak
during the early morning hours. This period corresponds with the sharp increase in heart
rate (HR) and blood pressure (BP) (morning BP surge) which takes place upon arising form
overnight sleep. Furthermore, the RAAS is activated in the morning, and may contribute to
morning BP surge and to morning increase in cardiovascular risk. BP control over the entire
24 hours dosing interval, including the early morning period (18 - 24 hrs post-dosing) is
critical in order to prevent cardiovascular events, thus providing a better protection to
patients with essential hypertension. Apart from the significance of establishing the 24-hour
BP lowering effect of an antihypertensive drug, it is fundamental to further investigate the
effect of a missing dose. Approximately 15 to 20% of hypertensive patients do not recall to
take their medication in average 3 days every month. During these periods, patients could be
on a higher risk of having a cardiovascular event resulting in a poorer long-term prognosis.
Therefore, it is crucial to establish the BP lowering effect of the antihypertensive
treatment beyond 24-hour of dose intake. Ambulatory blood pressure monitoring (ABPM) has
proven advantages compared to conventional BP measurement and ambulatory BP levels are
closely associated with target organ damage and clinical cardiovascular events in
hypertensive patients. However most of the studies using this technique have been conducted
with monitoring for a 24-hour period. In this study 48-hour ABPM will be utilized in order to
investigate the antihypertensive effect beyond 24 hours. This study was designed in order to
evaluate the BP lowering effect of valsartan compared to enalapril over 24 hours after
skipping one daily dose. Both drugs act on the RAAS and are widely use for the treatment of
hypertension. Enalapril was selected since a previous similar study was performed using it
as a comparison drug. An 8-week study with candesartan and enalapril was done to evaluate
their antihypertensive efficacy and their effect duration. However, this study had a
significant limitation, the effect of a missing dose was not evaluated after the whole 24
hours post missing dose period (48 hours after last taken dose), and as a result, it does not
imitate the real life situation of a missing dose. Therefore, we decided to perform the
present study with the purpose of further investigate the effect of these antihypertensive
treatments beyond 24 hours in patients with mild to moderate essential hypertension.
Minimum age: 18 Years.
Maximum age: N/A.
- Essential hypertension (grade 1-2)
- Severe hypertension
- Secondary hypertension
- Grade III/IV hypertensive retinopathy
- Type 1 diabetes
- Cerebrovascular or cardiovascular event during the last 12 months prior to inclusion.
- Pregnant or lactating females
- History of malignancy.
- shift workers
- intolerant to ABPM
Locations and Contacts
Hospital Clínico Universitario de Santiago, Santiago de Compostela 15706, Spain
Starting date: January 2005
Ending date: March 2007
Last updated: December 5, 2007