SAFE-CRP: Structural Alterations and Function of Endothelium in Cardiovascular Risk Patients
Information source: Boehringer Ingelheim Pharmaceuticals
Information obtained from ClinicalTrials.gov on March 21, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Hypertension; Coronary Arteriosclerosis
Intervention: telmisartan (Drug); Placebo (Drug)
Phase: Phase 4
Status: Terminated
Sponsored by: Boehringer Ingelheim Pharmaceuticals Official(s) and/or principal investigator(s):
Boehringer Ingelheim Study Coordinator, Study Chair, Affiliation: B.I. Pharma GmbH & Co. KG
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.
Clinical Details
Official title: Endothelial Dysfunction and Structural Alterations of Vessels in Cardiovascular Risk Patients - Approach of Amelioration by Treatment With Telmisartan
Study design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Efficacy Study
Primary outcome: The primary endpoint is a percentage change in atheroma volume (measured by IVUS; primary time-point = Visit 6, baseline = Visit 1).
Secondary outcome: 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)
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
Minimum age: 36 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion criteria:
1. > 35 years of age
2. History of coronary artery disease (CAD)
3. Ability to provide written informed consent
Exclusion criteria:
1. 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
2. Diastolic blood pressure > 110 mmHg or systolic blood pressure > 180 mmHg at any visit
during the study (run-in or randomised period)
3. 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
4. Bilateral renal artery stenosis, renal artery stenosis in a solitary kidney, patients
post-renal transplant or with only one kidney
5. Clinically relevant hypokalaemia or hyperkalaemia
6. Uncorrected volume depletion
7. Uncorrected sodium depletion
8. Primary aldosteronism
9. Hereditary fructose intolerance
10. Biliary obstructive disorders
11. Patients who have previously experienced symptoms characteristic of angioedema during
treatment with ACE inhibitors or angiotensin II receptor antagonists
12. History of drug or alcohol dependency within 6 months
13. Chronic administration of any medications known to affect blood pressure, except
medication allowed by the protocol
14. Any investigational therapy within one month of signing the informed consent form
15. Known hypersensitivity to any component of the formulation
16. 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
17. Stroke within the last 6 months
18. Myocardial infarction within the last 30 days
19. Cardiac surgery within the last 3 months
20. Hyperthyroidosis
21. Hemodynamically relevant valvular disease
22. Restrictive hypertrophic cardiomyopathy
23. Unstable angina pectoris
24. CAD with the indication of bypass surgery.
Locations and Contacts
Med. Hochschule Hannover, Hannover 30623, Germany
Universitätsklinikum Charité, Berlin 10117, Germany
Additional Information
Starting date: March 2001
Ending date: October 2004
Last updated: January 12, 2007
|
