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

This study has been completed.
Sponsor:
Collaborators:
Hospital Clinico Universitario de Santiago
Novartis
Information provided by:
University of Vigo
ClinicalTrials.gov Identifier:
NCT00302705
First received: March 13, 2006
Last updated: January 2, 2009
Last verified: January 2009
  Purpose

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.


Condition Intervention Phase
Hypertension
Drug: Valsartan, Enalapril
Device: Ambulatory blood pressure monitoring
Procedure: Missing one dose
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by University of Vigo:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To demonstrate that valsartan is more effective than enalapril in terms of systolic 24 hrs BP lowering after missing dose. [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • To show that valsartan has a more favorable effect than enalapril in smoothness index and through/peak ratio. [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • To demonstrate that valsartan offers better safety profile than enalapril. [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 150
Study Start Date: January 2005
Study Completion Date: March 2007
Primary Completion Date: March 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00302705

Locations
Spain
Hospital Clínico Universitario de Santiago
Santiago de Compostela, Spain, 15706
Sponsors and Collaborators
University of Vigo
Hospital Clinico Universitario de Santiago
Novartis
Investigators
Principal Investigator: Ramon C Hermida, Ph.D. University of Vigo
  More Information

No publications provided by University of Vigo

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Ramon C. Hermida, University of Vigo
ClinicalTrials.gov Identifier: NCT00302705     History of Changes
Other Study ID Numbers: VAL-489A2425, 2004-001725-25
Study First Received: March 13, 2006
Last Updated: January 2, 2009
Health Authority: Spain: Ministry of Health

Keywords provided by University of Vigo:
Ambulatory blood pressure monitoring
Valsartan
Enalapril
Missing dose

Additional relevant MeSH terms:
Hypertension
Cardiovascular Diseases
Vascular Diseases
Antihypertensive Agents
Enalapril
Enalaprilat
Valsartan
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Angiotensin-Converting Enzyme Inhibitors
Cardiovascular Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protease Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014