Study to Determine if Olmesartan Medoxomil Has the Potential to Benefit the Cardiovascular System in Terms of Arterial Protection (ArtStiff)

Effect of Olmesartan Medoxomil on Arterial Stiffness and Thickness in Subjects With Metabolic Syndrome

This study will analyse the dose-dependent effect of olmesartan medoxomil on the change in arterial stiffness in subjects with hypertension and metabolic syndrome

Study Overview

• Status: Completed
• Conditions: Hypertension; Metabolic Syndrome
• Intervention / Treatment: Drug: placebo; Drug: olmesartan medoxomil

• Study Type: Interventional
• Enrollment (Actual): 133
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Ghent, Belgium
• Germany
  • Nurnberg, Germany
• Italy
  • Monza, Italy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female outpatients
• Age greater than or equal to 18 years and less than or equal to 75 years
• Hypertension and metabolic syndrome defined, according to the ATP III/IDF 2005 and ESH/ESC 2007 definitions, as BP greater than or equal to 130/85 mmHg and <150/95 mmHg (i.e. untreated high normal BP or "low range" mild hypertension) and at least 2 of the following traits at:
• Abdominal obesity (waist circumference >102 cm for men and >88 cm for women)
• Triglyceride level greater than or equal to 150 mg/dL
• High density lipoprotein (HDL) <40 mg/dL for men and <50 mg/dL for women
• Fasting blood glucose greater than or equal to 110 mg/dL and <126 mg/dL (i.e. no type 2 diabetes)
• No anti-hypertensive treatment or treatment with only one anti-hypertensive medication within the last 3 months. Note: treatment with angiotensin II receptor blockers (ARB)or angiotensin-converting enzyme inhibitors (ACE) is not allowed within the last 6 months.

Exclusion Criteria:

• Pregnant or lactating female (prerequisite for female subjects of childbearing potential: adequate contraception)
• Type 1 and type 2 diabetes
• "High range" mild hypertension (i.e. systolic blood pressure [SBP]: 150 - <160 mmHg and /or diastolic blood pressure [DBP]: 95 - <100 mmHg)
• Moderate (SBP: 160 - 179 mmHg and DBP: 100 - 109 mmHg), severe (SBP: greater than or equal to 180 mmHg and/or greater than or equal to 110 mmHg), or resistant (hypertension resistant to treatment)hypertension
• Secondary hypertension of any aetiology, such as renal disease, pheochromocytoma, or Cushing's syndrome

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 1; A 3-week placebo run-in period.	Drug: placebo; dosage form: tablet; frequency: daily; duration: 3 weeks
Experimental: 2; Olmesartan medoxomil oral tablets, at lowest study dosage for 52-week double-blind treatment period	Drug: olmesartan medoxomil; dosage form: oral tablet; frequency: daily; duration: 52 weeks
Experimental: 3; Olmesartan medoxomil oral tablets at the lowest dosage for 4 weeks followed by a higher dosage for 48 weeks.	Drug: olmesartan medoxomil; dosage form: oral tablet; frequency: daily; duration: 52 weeks
Experimental: 4; Olmesartan medoxomil oral tablets at the lowest dosage for 4 weeks followed by a higher dosage for 4 weeks followed by the highest study dose for 44 weeks.	Drug: olmesartan medoxomil; dosage form: oral tablet; frequency: daily; duration: 52 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The change from baseline in carotid-femoral pulse wave velocity (PWV)	Up to 1 year of double-blind treatment
The change from baseline in carotid-femoral PWV, after adjustment for change from baseline in mean blood pressure (MBP)as measured at the same visit	Up to 1 year of double-blind treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
On blood pressure (BP) lowering, assessed by conventional BP measurement and 24h ambulatory BP measurement (24h-ABPM)	Up to 1 year of double-blind treatment
On central pulse pressure (PP) and augmentation index (AI)	Up to 1 year of double-blind treatment
On common carotid stiffness, intima-media thickness (IMT), and internal diameter	Up to 1 year of double-blind treatment

Collaborators and Investigators

• Sponsor: Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company

Publications and helpful links

General Publications

• Laurent S, Boutouyrie P; Vascular Mechanism Collaboration. Dose-dependent arterial destiffening and inward remodeling after olmesartan in hypertensives with metabolic syndrome. Hypertension. 2014 Oct;64(4):709-16. doi: 10.1161/HYPERTENSIONAHA.114.03282. Epub 2014 Jul 7.

Study record dates

Study Major Dates

• Study Start: August 1, 2008
• Primary Completion (Actual): May 1, 2011
• Study Completion (Actual): May 1, 2011

Study Registration Dates

• First Submitted: May 8, 2008
• First Submitted That Met QC Criteria: May 12, 2008
• First Posted (Estimate): May 13, 2008

Study Record Updates

• Last Update Posted (Actual): December 24, 2018
• Last Update Submitted That Met QC Criteria: December 20, 2018
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Keywords: Arterial stiffness; Vascular protection
• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Disease; Insulin Resistance; Hyperinsulinism; Syndrome; Metabolic Syndrome; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Olmesartan; Olmesartan Medoxomil
• Other Study ID Numbers: DSE-866/47; 2007-003131-23 EudraCT number

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
• IPD Sharing Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• IPD Sharing Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR