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
  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 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
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)

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Change of intima/media ratio in the femoral artery measured by intravascular ultrasound (IVUS) [ Time Frame: after 39 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 22
Study Start Date: March 2001
Estimated Study Completion Date: October 2004
Primary Completion Date: October 2004 (Final data collection date for primary outcome measure)
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:

  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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
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: October 31, 2013
Health Authority: Germany: BfArM Bundesinstitut für Arzneimittel und Medizinprodukte

Additional relevant MeSH terms:
Arteriosclerosis
Atherosclerosis
Coronary Artery Disease
Myocardial Ischemia
Hypertension
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Coronary Disease
Heart Diseases
Telmisartan
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 27, 2014