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

Sponsor:	Boehringer Ingelheim Pharmaceuticals
Information provided by:	Boehringer Ingelheim Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00274105

Purpose

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.

Condition	Intervention	Phase
Hypertension Coronary Arteriosclerosis	Drug: telmisartan Drug: Placebo	Phase IV

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double-Blind Primary Purpose: Treatment
Official Title:	Endothelial Dysfunction and Structural Alterations of Vessels in Cardiovascular Risk Patients - Approach of Amelioration by Treatment With Telmisartan

Resource links provided by NLM:

MedlinePlus related topics: Atherosclerosis Coronary Artery Disease High Blood Pressure

Drug Information available for: Telmisartan

U.S. FDA Resources

Further study details as provided by Boehringer Ingelheim Pharmaceuticals:

Primary Outcome Measures:

The primary endpoint is a percentage change in atheroma volume (measured by IVUS; primary time-point = Visit 6, baseline = Visit 1).

Secondary Outcome Measures:

The secondary endpoints are change in total atheroma volume in percentage atheroma volume in flow dependent dilatation (FDD) provoked by intraarterial infusion of Acetylcholin change in CRP, MCP-1, oxLDL antibodies, sPLA2 (amount and activity)

Estimated Enrollment:	30
Study Start Date:	March 2001
Estimated Study Completion Date:	October 2004

Detailed Description:

Methodology:

2:1 randomised, double-blind and placebo-controlled parallel-group design

Planned/actual number of subjects:

Enrolled: 30/33, randomised: 30/22, completed: 30/15

Duration of treatment:

9 months: telmisartan (80 mg) or Placebo (80 mg)

Study Hypothesis:

The trial is designed as a group comparison of telmisartan 80 mg and placebo, where the treatment groups are randomised in 2:1 relation, to investigate the efficacy of telmisartan on structural alterations and endothelial dysfunction as measured as the percentage change from baseline after 36 weeks of treatment of the atheroma volume in the femoral artery using IVUS .

Secondary endpoints are the changes from baseline in the flow dependent dilatation after a acetylcholine challenge which follows a nitro-glycerin bolus, the change of the total atheroma volume, the percentage atheroma volume measured by intravascular ultrasound (IVUS) and the infalmmatory parameters MCP-1, CRP, ox LDL antibodies and sPLA2 activity and amount.

In an analysis of covariance using baseline as covariate all endpoints will be investigated. If the assumptions of normal distribution are not fulfilled, nonparametric methods will be applied (Wilcoxon-Mann-Whitney test).

Comparison(s):

Placebo 80 mg

Eligibility

Ages Eligible for Study:	36 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion criteria:

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

Exclusion criteria:

Pre-menopausal women (last menstruation < 1 year prior to start of the screening visit) who:
1. are not surgically sterile; and/or
2. are nursing
3. 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:
1. SGPT(ALT) or SGOT(AST) > than 2 times the upper limit of normal range
2. 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
Patients who have previously experienced symptoms characteristic of angioedema during treatment with ACE inhibitors or angiotensin II receptor antagonists
History of drug or alcohol dependency within 6 months
Chronic administration of any medications known to affect blood pressure, except medication allowed by the protocol
Any investigational therapy within one month of signing the informed consent form
Known hypersensitivity to any component of the formulation
Any other clinical condition which, in the opinion of the principal investigator, would not allow safe completion of the protocol and safe administration of telmisartan
Stroke within the last 6 months
Myocardial infarction within the last 30 days
Cardiac surgery within the last 3 months
Hyperthyroidosis
Hemodynamically relevant valvular disease
Restrictive hypertrophic cardiomyopathy
Unstable angina pectoris
CAD with the indication of bypass surgery.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00274105

Locations

Germany
Universitätsklinikum Charité
Berlin, Germany, 10117
Med. Hochschule Hannover
Hannover, Germany, 30623

Sponsors and Collaborators

Boehringer Ingelheim Pharmaceuticals

Investigators

Study Chair:

Boehringer Ingelheim Study Coordinator

B.I. Pharma GmbH & Co. KG

More Information

No publications provided

ClinicalTrials.gov Identifier:	NCT00274105 History of Changes
Other Study ID Numbers:	502.350
Study First Received:	January 9, 2006
Last Updated:	January 12, 2007
Health Authority:	Germany: BfArM Bundesinstitut für Arzneimittel und Medizinprodukte

Additional relevant MeSH terms:

Arteriosclerosis
Coronary Artery Disease
Myocardial Ischemia
Hypertension
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Coronary Disease
Heart Diseases

Telmisartan
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on February 09, 2012