Comparison of the Antihypertensive Efficacy of Valsartan and Enalapril After Missing One Dose

Phase 4

Completed

• Conditions: Hypertension
• Interventions: Drug: Valsartan, Enalapril; Device: Ambulatory blood pressure monitoring; Procedure: Missing one dose

• Registration Number: NCT00302705
• Lead Sponsor: University of Vigo

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.

Study Timeline

• Study Start: 2005-01
• Study First Submitted: 2006-03-13
• Study First Submitted QC: 2006-03-13
• Study First Posted: 2006-03-14
• Primary Completion: 2007-03
• Study Completion: 2007-03
• Status Verified: 2009-01
• Last Update Submitted: 2009-01-02
• Last Update Posted: 2009-01-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 150

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Valsartan	Valsartan, Enalapril	160 mg/day on awakening
Valsartan	Ambulatory blood pressure monitoring	160 mg/day on awakening
Valsartan	Missing one dose	160 mg/day on awakening
Enalapril	Valsartan, Enalapril	10-20 mg/day on awakening
Enalapril	Ambulatory blood pressure monitoring	10-20 mg/day on awakening
Enalapril	Missing one dose	10-20 mg/day on awakening

Primary Outcome Measures

Name	Time	Method
To demonstrate the efficacy of valsartan by testing the hypothesis of superior 24 hrs diastolic BP lowering after missing dose compared with enalapril.	16 weeks

Secondary Outcome Measures

Name	Time	Method
To show that valsartan has a more favorable effect than enalapril in smoothness index and through/peak ratio.	16 weeks
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.	16 weeks
To demonstrate that valsartan offers better safety profile than enalapril.	16 weeks
To demonstrate that valsartan is more effective than enalapril in terms of systolic 24 hrs BP lowering after missing dose.	16 weeks

Trial Locations

Locations (1)

Hospital Clínico Universitario de Santiago; 🇪🇸 Santiago de Compostela, Spain