HypertensionPhase 4NCT00274105
SAFE-CRP: Structural Alterations and Function of Endothelium in Cardiovascular Risk Patients
A Phase 4 study testing telmisartan in people with Hypertension and Coronary Arteriosclerosis, run by Boehringer Ingelheim at 2 sites in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 36 years and older
- Conditions the study is for
- Hypertension, Coronary Arteriosclerosis
- What is being tested?
- telmisartan
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 22 participants
- Where
- 2 sitesGermany
- Study dates
- 1 Mar 2001to 1 Oct 2004
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 36 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- > 35 years of age
- History of coronary artery disease (CAD)
- Ability to provide written informed consent
Who cannot join
- Pre-menopausal women (last menstruation < 1 year prior to start of the screening visit) who:
- are not surgically sterile; and/or
- are nursing
- 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
- Diastolic blood pressure > 110 mmHg or systolic blood pressure > 180 mmHg at any visit during the study (run-in or randomised period)
- Hepatic and/or renal dysfunction as defined by the following laboratory parameters:
Show all 29Show fewer
- SGPT(ALT) or SGOT(AST) > than 2 times the upper limit of normal range
- Serum creatinine > 2.3 mg/dL
- Bilateral renal artery stenosis, renal artery stenosis in a solitary kidney, patients post-renal transplant or with only one kidney
- Clinically relevant hypokalaemia or hyperkalaemia
- Uncorrected volume depletion
- Uncorrected sodium depletion
- Primary aldosteronism
- Hereditary fructose intolerance
- Biliary obstructive disorders
- Patients who have previously experienced symptoms characteristic of angioedema during treatment with ACE inhibitors or angiotensin II receptor antagonists
- History of drug or alcohol dependency within 6 months
- Chronic administration of any medications known to affect blood pressure, except medication allowed by the protocol
- Any investigational therapy within one month of signing the informed consent form
- Known hypersensitivity to any component of the formulation
- 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
- Stroke within the last 6 months
- Myocardial infarction within the last 30 days
- Cardiac surgery within the last 3 months
- Hyperthyroidosis
- Hemodynamically relevant valvular disease
- Restrictive hypertrophic cardiomyopathy
- Unstable angina pectoris
- CAD with the indication of bypass surgery.
Trial locations and contacts
2 sites in 1 country.
Germany2 sites
Universitätsklinikum Charité
Berlin, 10117
Med. Hochschule Hannover
Hanover, 30623
About this study
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)
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.
Read the 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
- Conditions
- Hypertension, Coronary Arteriosclerosis
- Being tested
- telmisartan, Placebo
- Medical subject headings
- Hypertension, Coronary Artery Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
telmisartanDrug
PlaceboDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Change of intima/media ratio in the femoral artery measured by intravascular ultrasound (IVUS)
Measured: after 39 weeks
Secondary outcomes (4)
Change in plaque size in the femoral artery measured by IVUS
Measured: after 39 weeks
Increase in FDD (Flow dependent dilation) stimulated by intra-arterial infusion of Acetylcholine (ACH)
Measured: after 39 weeks
Change in serum inflammatory markers (CRP, MCP-1, oxLDL antibodies, and VCAM)
Measured: after 39 weeks
Change in seated blood pressure (BP) at trough
Measured: after 39 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jan 2006 (estimated)
- Study start1 Mar 2001
- Primary completion1 Oct 2004
- Study completion1 Oct 2004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HypertensionStudies of the same condition, open and under way.
- More trials run by Boehringer IngelheimThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Enrolment
- 22 participants
Sponsor and investigators
- Lead sponsor
- Boehringer Ingelheim
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Boehringer Ingelheim Study Coordinator, Study chair, B.I. Pharma GmbH & Co. KG
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00274105
- Sponsor's protocol ID
- 502.350
- Status last verified
- Jan 2025
- First submitted
- 9 Jan 2006
- Last updated
- 23 Jan 2025
- Results posted
- No
- Individual data sharing
- No: Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents. Exceptions might apply, e.g. studies in products where Boehringer Ingelheim is not the license holder; studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; studies conducted in a single center or targeting rare diseases (in case of low number of patients and therefore limitations with anonymization). For more details refer to: https://www.mystudywindow.com/msw/datatransparency
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT00274105
- Acronym / sponsor ID
- 502.350
- Conditions
- Hypertension, Coronary Arteriosclerosis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 22 participants
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- 1 Mar 2001 (actual)
- Primary completion
- 1 Oct 2004 (actual)
- Study completion
- 1 Oct 2004 (actual)
- First posted
- 10 Jan 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
Who may qualify
- Ages
- 36 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- > 35 years of age
- History of coronary artery disease (CAD)
- Ability to provide written informed consent
Key exclusion criteria (29 listed)
- Pre-menopausal women (last menstruation < 1 year prior to start of the screening visit) who:
- Diastolic blood pressure > 110 mmHg or systolic blood pressure > 180 mmHg at any visit during the study (run-in or randomised period)
- Hepatic and/or renal dysfunction as defined by the following laboratory parameters:
- Bilateral renal artery stenosis, renal artery stenosis in a solitary kidney, patients post-renal transplant or with only one kidney
- Clinically relevant hypokalaemia or hyperkalaemia
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| telmisartan | Drug | – |
| Placebo | Drug | – |
Primary outcome
Change of intima/media ratio in the femoral artery measured by intravascular ultrasound (IVUS)
Time frame: after 39 weeks
4 secondary outcomes
Change in plaque size in the femoral artery measured by IVUS
Time frame: after 39 weeks
Increase in FDD (Flow dependent dilation) stimulated by intra-arterial infusion of Acetylcholine (ACH)
Time frame: after 39 weeks
Change in serum inflammatory markers (CRP, MCP-1, oxLDL antibodies, and VCAM)
Time frame: after 39 weeks
Change in seated blood pressure (BP) at trough
Time frame: after 39 weeks
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2025.
- Individual participant dataSharing planned: No. Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents. Exceptions might apply, e.g. studies in products where Boehringer Ingelheim is not the license holder; studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; studies conducted in a single center or targeting rare diseases (in case of low number of patients and therefore limitations with anonymization). For more details refer to: https://www.mystudywindow.com/msw/datatransparency
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Boehringer Ingelheim Study Coordinator study chair
B.I. Pharma GmbH & Co. KG
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing telmisartan in people with Hypertension and Coronary Arteriosclerosis, run by Boehringer Ingelheim at 2 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 23 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change of intima/media ratio in the femoral artery measured by intravascular ultrasound (IVUS) (time frame: after 39 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2025.