Clinical trial NCT00382213: A Randomized, Double Blind Study To Compare The Effects Of Olmesartan Medoxomil Versus Placebo In Patients With Established Atherosclerosis
Official title: A Randomized, Double Blind Study To Compare The Effects Of Olmesartan Medoxomil Versus Placebo In Patients With Established Atherosclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Atherosclerosis
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
First posted: 2006-09-28
Enrollment: 210
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: The purpose of this study is to determine the efficacy of treatment with olmesartan medoxomil, an Angiotensin Receptor Blocker, compared to placebo on the blood levels of surrogate markers of vascular inflammation for atherosclerotic disease. Patients will be randomized to receive either olmesartan medoxomil or placebo for one year.


Eligibility criteria: Inclusion Criteria:

* Males or Females age less than or equal to 18
* TEE-defined Grade III or IV atherosclerotic disease of the thoracic aorta documented within the previous 90 days, or established atherosclerotic disease of the lower extremities as demonstrated by:

  * a history of lower extremity peripheral vascular surgery for obstructive atherosclerotic disease, or
  * a history of lower extremity peripheral arterial angioplasty for obstructive atherosclerotic disease, or
  * a history of lower extremity amputation secondary to atherosclerotic disease, or
  * an ABI \<0.90 within the previous 90 days, or
  * a history of claudication in patients with documented coronary artery disease (i.e., history of myocardial infarction, coronary revascularization, or coronary angiography demonstrating at least one obstructive coronary lesion with a 50% or greater stenosis).

Exclusion Criteria:

* Women of childbearing age who do not agree to utilize protocol approved contraceptive methods.
* Average pre-dose SBP \< 100 or DBP \< 60.
* Patients with any serious disorder including cardiovascular (ventricular arrhythmias, valvular disease or implantable defibrillator), renal, pulmonary, hepatic, gastrointestinal, endocrine/metabolic (excluding patients with controlled diabetes mellitus), hematologic/oncologic (including an active malignancy other than basal cell carcinoma or non-metastatic prostate cancer), neurologic, and psychiatric diseases.
* Patients with a history of MI, PTCA, CABG, heart failure, CVA or TIA within the last 30 days.

Primary outcomes:
measure: The primary endpoint for the determination of efficacy will be a composite of
measure: ten circulating surrogate markers of atherosclerosis for vascular inflammation.
measure: The surrogate markers of vascular inflammation to be used will include
measure: C-reactive protein, MCP-1, M-CSF, VCAM-1, TNFα, IL-1, E-Selectin, ICAM-1, IL-6
measure: and MMP-9.
Secondary outcomes:
measure: Individual circulating surrogate markers of atherosclerosis listed above
measure: (C-reactive protein, MCP-1, M-CSF, VCAM-1, TNFα, IL-1, E-Selectin, ICAM-1,
measure: IL-6 and MMP).
measure: Serum levels of TGF-β, PDGF, HGF, and PAI-1.
measure: The ratio of reduced to oxidized glutathione in the plasma as an indicator
measure: of oxidative stress (GSH/GSSG ratio).
measure: Composite of adhesion markers (VCAM-1, E-selectin, and ICAM-1).
measure: Composite of chemoattractant markers (MCP-1, M-CSF).
measure: Composite of Growth Factor Markers (PDGF, HGF, TGF-β).
measure: Assessment of atherosclerotic disease severity of the thoracic aorta as
measure: determined by transesophageal echocardiography (TEE) in patients enrolled
measure: on the basis of TEE-defined aortic atherosclerosis.
measure: Assessment of atherosclerotic disease severity of the peripheral arteries
measure: of the lower extremities as determined by the ankle brachial index (ABI).
measure: Endothelial function as determined by brachial artery diameter responses to
measure: hyperemic flow.
Other outcomes:
Locations:
Study officials:
References: