Clinical trial NCT00302705: Comparison of the Antihypertensive Efficacy of Valsartan and Enalapril After Missing One 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hypertension
Keywords: Ambulatory blood pressure monitoring
Valsartan
Enalapril
Missing dose
Lead sponsor: University of Vigo
Sponsor class: OTHER
Collaborators: name: Hospital Clinico Universitario de Santiago
name: Novartis
First posted: 2006-03-14
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Essential hypertension (grade 1-2)

Exclusion Criteria:

* 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

Primary outcomes:
measure: To demonstrate the efficacy of valsartan by testing the hypothesis of superior 24 hrs diastolic BP lowering after missing dose compared with enalapril.
timeFrame: 16 weeks
Secondary outcomes:
measure: To demonstrate that valsartan is more effective than enalapril in terms of systolic 24 hrs BP lowering after missing dose.
timeFrame: 16 weeks
measure: 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.
timeFrame: 16 weeks
measure: To show that valsartan has a more favorable effect than enalapril in smoothness index and through/peak ratio.
timeFrame: 16 weeks
measure: To demonstrate that valsartan offers better safety profile than enalapril.
timeFrame: 16 weeks
Other outcomes:
Locations:
city: Santiago de Compostela
country: Spain
facility: Hospital Clínico Universitario de Santiago
Study officials:
affiliation: University of Vigo
name: Ramon C Hermida, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hermida RC, Ayala DE, Khder Y, Calvo C. Ambulatory blood pressure-lowering effects of valsartan and enalapril after a missed dose in previously untreated patients with hypertension: a prospective, randomized, open-label, blinded end-point trial. Clin Ther. 2008 Jan;30(1):108-20. doi: 10.1016/j.clinthera.2008.01.012.