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

January 2, 2009 updated by: University of Vigo

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

150

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Santiago de Compostela, Spain, 15706
        • Hospital Clínico Universitario de Santiago

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Valsartan
160 mg/day on awakening
Drug: Valsartan, Enalapril
160 mg valsartan versus 10-20 mg enalapril
Device: Ambulatory blood pressure monitoring
Blood pressure measured at 20-min intervals from 07:00 to 23:00 hours and at 30-min intervals at night for 48 consecutive hours
Procedure: Missing one dose
Patients skip the dose the second day of monitoring
Active Comparator: Enalapril
10-20 mg/day on awakening
Drug: Valsartan, Enalapril
160 mg valsartan versus 10-20 mg enalapril
Device: Ambulatory blood pressure monitoring
Blood pressure measured at 20-min intervals from 07:00 to 23:00 hours and at 30-min intervals at night for 48 consecutive hours
Procedure: Missing one dose
Patients skip the dose the second day of monitoring

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Vigo

Collaborators

Novartis
Hospital Clinico Universitario de Santiago

Investigators

  • Principal Investigator: Ramon C Hermida, Ph.D., University of Vigo

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2005

Primary Completion (Actual)

March 1, 2007

Study Completion (Actual)

March 1, 2007

Study Registration Dates

First Submitted

March 13, 2006

First Submitted That Met QC Criteria

March 13, 2006

First Posted (Estimate)

March 14, 2006

Study Record Updates

Last Update Posted (Estimate)

January 5, 2009

Last Update Submitted That Met QC Criteria

January 2, 2009

Last Verified

January 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VAL-489A2425
  • 2004-001725-25

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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