SAFE-CRP: Structural Alterations and Function of Endothelium in Cardiovascular Risk Patients

NCT00274105 | Terminated Phase 4

• 1 other identifier: 502.350
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 2

Brief Summary

The aim of this trial is to evaluate the efficacy and safety of telmisartan 80 mg administered once daily in patients with documented coronary artery disease (CAD) and a probably cardiovascular risk profile concerning the amelioration of structural alterations and endothelial function. The primary objective of this trial is to evaluate the efficacy in particular with regard to the percentage change of atheroma volume in the femoral artery.The secondary objective is to evaluate the change in the plaque size- assessed by intravascular ultrasound, the increase in Flow Dependent Dilation provoked by intraarterial infusion of three increasing concentrations of Acetylcholine, and the change in seated systolic blood pressure. Endothelial dysfunction is a primary event in atherogenesis and all known cardiovascular risk factors have been associated with endothelial dysfunction before atherosclerotic vascular disease manifests itself clinically. Pivotal to endothelial dysfunction is a disturbance in the function of endothelium-derived nitric oxide (NO). Recently, it could be shown that acute and chronic angiotensin-1 receptor antagonism reversed endothelial dysfunction in atherosclerosis. In experimental atherosclerosis, AT1 receptor blockade appears to have protective effects. Respective potential mechanisms include the prevention of endothelial injury, the augmentation of NO activity, the inhibition of lipid peroxidation and an antiproliferative effect. These findings together with the most recent data that losartan improves endothelial function and NO activity suggest that AT1 receptor antagonism may also be antiatherogenic in patients with atherosclerosis. Angiotensin II influences smooth muscle cell migration, hyperplasia, and hypertrophy. Angiotensin II also enhances production of local superoxide anion, which will inactivate nitric oxide. Inhibition of these reactions by the AT1-Blocker telmisartan may therefore interfere with atherosclerotic plaque formation.

Conditions

Hypertension; Coronary Arteriosclerosis

Outcome Measures

Primary Outcomes (1)

• Change of intima/media ratio in the femoral artery measured by intravascular ultrasound (IVUS)

  after 39 weeks

Secondary Outcomes (4)

• Change in plaque size in the femoral artery measured by IVUS

  after 39 weeks

• Increase in FDD (Flow dependent dilation) stimulated by intra-arterial infusion of Acetylcholine (ACH)

  after 39 weeks

• Change in serum inflammatory markers (CRP, MCP-1, oxLDL antibodies, and VCAM)

  after 39 weeks

• Change in seated blood pressure (BP) at trough

  after 39 weeks

Interventions

telmisartan DRUG

Placebo DRUG

Eligibility Criteria

• Age: 36 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \> 35 years of age
• History of coronary artery disease (CAD)
• Ability to provide written informed consent

You may not qualify if:

• Pre-menopausal women (last menstruation \< 1 year prior to start of the screening visit) who:
• are not surgically sterile; and/or
• are nursing
• are of child-bearing potential and are NOT practising acceptable means of birth control, do NOT plan to continue using this method throughout the study and do NOT agree to submit to periodic pregnancy testing during participation in studies of \> 3-months duration. Acceptable methods of birth control include oral, implantable or injectable contraceptives
• Diastolic blood pressure \> 110 mmHg or systolic blood pressure \> 180 mmHg at any visit during the study (run-in or randomised period)
• Hepatic and/or renal dysfunction as defined by the following laboratory parameters:
• SGPT(ALT) or SGOT(AST) \> than 2 times the upper limit of normal range
• Serum creatinine \> 2.3 mg/dL
• Bilateral renal artery stenosis, renal artery stenosis in a solitary kidney, patients post-renal transplant or with only one kidney
• Clinically relevant hypokalaemia or hyperkalaemia
• Uncorrected volume depletion
• Uncorrected sodium depletion
• Primary aldosteronism
• Hereditary fructose intolerance
• Biliary obstructive disorders

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (2)

Universitätsklinikum Charité

Berlin, 10117, Germany

Location

Med. Hochschule Hannover

Hanover, 30623, Germany

Location

MeSH Terms

Conditions

Hypertension; Coronary Artery Disease

Interventions

Telmisartan

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Coronary Disease; Myocardial Ischemia; Heart Diseases; Arteriosclerosis; Arterial Occlusive Diseases

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Boehringer Ingelheim Study Coordinator

  B.I. Pharma GmbH & Co. KG

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2006
• First Posted: January 10, 2006
• Study Start: March 1, 2001
• Primary Completion: October 1, 2004
• Study Completion: October 1, 2004
• Last Updated: January 23, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

DE (2)