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

This study has been terminated.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00274105
First received: January 9, 2006
Last updated: October 31, 2013
Last verified: October 2013

January 9, 2006
October 31, 2013
March 2001
October 2004   (final data collection date for primary outcome measure)
Change of intima/media ratio in the femoral artery measured by intravascular ultrasound (IVUS) [ Time Frame: after 39 weeks ] [ Designated as safety issue: No ]
The primary endpoint is a percentage change in atheroma volume (measured by IVUS; primary time-point = Visit 6, baseline = Visit 1).
Complete list of historical versions of study NCT00274105 on ClinicalTrials.gov Archive Site
  • 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 ]
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)
Not Provided
Not Provided
 
SAFE-CRP: Structural Alterations and Function of Endothelium in Cardiovascular Risk Patients
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)

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.

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

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
  • Hypertension
  • Coronary Arteriosclerosis
  • Drug: telmisartan
  • Drug: Placebo
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
22
October 2004
October 2004   (final data collection date for primary outcome measure)

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.
Both
36 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Germany
 
NCT00274105
502.350
Not Provided
Not Provided
Boehringer Ingelheim
Not Provided
Study Chair: Boehringer Ingelheim Study Coordinator B.I. Pharma GmbH & Co. KG
Boehringer Ingelheim
October 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP