Ignite Creation Date:
2024-05-05 @ 4:35 PM
Last Modification Date:
2024-10-26 @ 9:22 AM
Study NCT ID:
NCT00274105
Status:
TERMINATED
Last Update Posted:
2013-11-01
First Post:
2006-01-09
Brief Title:
SAFE-CRP Structural Alterations and Function of Endothelium in Cardiovascular Risk Patients
Sponsor:
Boehringer Ingelheim
Organization:
Boehringer Ingelheim
Study Overview
Official Title:
A Double Blind 21 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
Status:
TERMINATED
Status Verified Date:
2013-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 arteryThe 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
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 arteryThe 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
Detailed Description:
Methodology
21 randomised double-blind and placebo-controlled parallel-group design
Plannedactual number of subjects
Enrolled 3033 randomised 3022 completed 3015
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 21 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
Comparisons
Placebo 80 mg
21 randomised double-blind and placebo-controlled parallel-group design
Plannedactual number of subjects
Enrolled 3033 randomised 3022 completed 3015
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 21 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
Comparisons
Placebo 80 mg
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None