SAFE-CRP: Structural Alterations and Function of Endothelium in Cardiovascular Risk Patients
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
|Official Title:||A Double Blind, 2:1 Randomised Monocentre Study to Investigate the Efficacy and Safety of Telmisartan (80 mg qd) Concerning the Amelioration of Structural Alterations and Function of Endothelium in Cardiovascular Risk Patients (SAFE-CRP: Structural Alterations and Function of Endothelium in Cardiovascular Risk Patients)|
- Change of intima/media ratio in the femoral artery measured by intravascular ultrasound (IVUS) [ Time Frame: after 39 weeks ] [ Designated as safety issue: No ]
- Change in plaque size in the femoral artery measured by IVUS [ Time Frame: after 39 weeks ] [ Designated as safety issue: No ]
- Increase in FDD (Flow dependent dilation) stimulated by intra-arterial infusion of Acetylcholine (ACH) [ Time Frame: after 39 weeks ] [ Designated as safety issue: No ]
- Change in serum inflammatory markers (CRP, MCP-1, oxLDL antibodies, and VCAM) [ Time Frame: after 39 weeks ] [ Designated as safety issue: No ]
- Change in seated blood pressure (BP) at trough [ Time Frame: after 39 weeks ] [ Designated as safety issue: No ]
|Study Start Date:||March 2001|
|Estimated Study Completion Date:||October 2004|
|Primary Completion Date:||October 2004 (Final data collection date for primary outcome measure)|
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)
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).
Placebo 80 mg
|Berlin, Germany, 10117|
|Med. Hochschule Hannover|
|Hannover, Germany, 30623|
|Study Chair:||Boehringer Ingelheim Study Coordinator||B.I. Pharma GmbH & Co. KG|