TEAMSTAprotect: Telmisartan, Amlodipine and Flow Mediated Dilation

Sponsor

Johannes Gutenberg University Mainz (Other)

Overall Status

Unknown status

CT.gov ID

NCT01180205

Collaborator

(none)

576

Enrollment

Location

Arms

Duration (Months)

41.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To show superior effects of the combination Telmisartan and Amlodipine (T and A) vs Olmesartan and Hydrochlorothiazide (O and HCTZ) on endothelial dysfunction as measured by flow mediated dilation (FMD) in hypertensive at risk patients beyond bloodpressure BP (equal BP in both arms; target BP <140/90 mmHg (<130/80 mmHg for renally impaired and/ or diabetic patients). To investigate the effects of T and A vs O and HCTZ in reducing arterial stiffness and carotid atherosclerotic plaques.

Condition or Disease	Intervention/Treatment	Phase
Hypertension	Drug: Telmisartan Drug: Amlodipine Drug: Olmesartan medoxomil Drug: Hydrochlorothiazide	Phase 4

Detailed Description

This is a Phase IV, randomised, double-blind, forced- titration, active controlled, mono-center study to primarily compare the effects on endothelial function of the combination of telmisartan and amlodipine versus olmesartan and hydrochlorothiazide in hypertensive patients at risk beyond blood pressure. Additionally, key secondary endpoints for this trial are the changes in plaque and intima media complex echogenicity and the change in arterial stiffness after 26 weeks of treatment.

576 patients will be included in the study after a screening period of two weeks and then randomised in one of the two treatment groups. Pretreatment with ARBs, ACE-Inhibitors, amlodipine and diuretics will be stopped last day before visit 2. At visit 2 the treatment with either telmisartan and amlodipine or olmesartan and hydrochlorothiazide starts, so that no medication is stopped without having been replaced by the study medication. After two weeks treatment all patients will be up-titrated and having the maintenance dose for the following 24 weeks. The trial will be performed at one center in Germany with access to patients with hypertension. Patients will be recruited from the Department of Cardiology of the university Mainz. There will be a promotion flyer and an information booklet about the study for cardiologists practicising near Mainz, who like to sent their patient to the study center. Sponsor of the trial is the university Mainz.

Stefan Blankenberg, MD has been designated as Principal Investigator for this national, mono-center trial.

The study will be completed when the last patient had his last visit and the telephone follow

up two weeks later will be performed. This latest patient contact is defined as end of trial.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

576 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A TElmisartan and AMlodipine STudy to Assess the Cardiovascular PROTECTive Effects as Measured by Endothelial Dysfunction in Hypertensive at Risk Patients Beyond Blood Pressure

Study Start Date :

Aug 1, 2010

Anticipated Primary Completion Date :

Oct 1, 2011

Anticipated Study Completion Date :

Oct 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: T/A Telmisartan + Amlopidpine	Drug: Telmisartan Telmisartan (80 mg ,Tablets, QD, p.o., 26 weeks) Other Names: MICARDIS® (Telmisartan) Drug: Amlodipine Amlodpine 5 mg po 14 days, the forced - titration to 10 mg po for 24 weeks Other Names: Norvasc
Active Comparator: O/HCT Olmesartan + Hydrochlorothiazide	Drug: Olmesartan medoxomil Olmesartan 40 mg po for 26 weeks Other Names: Olmetec Drug: Hydrochlorothiazide HCT 12,5 mg po for 14 days, then 25 mg po for 24 weeks

Arm

Intervention/Treatment

Active Comparator: T/A

Telmisartan + Amlopidpine

Drug: Telmisartan

Telmisartan (80 mg ,Tablets, QD, p.o., 26 weeks)

Other Names:

MICARDIS® (Telmisartan)

Drug: Amlodipine

Amlodpine 5 mg po 14 days, the forced - titration to 10 mg po for 24 weeks

Other Names:

Norvasc

Active Comparator: O/HCT

Olmesartan + Hydrochlorothiazide

Drug: Olmesartan medoxomil

Olmesartan 40 mg po for 26 weeks

Other Names:

Olmetec

Drug: Hydrochlorothiazide

HCT 12,5 mg po for 14 days, then 25 mg po for 24 weeks

Outcome Measures

Primary Outcome Measures

FMD flow mediated dilation [baseline]
The overall mean improvement following 26 weeks of treatment in FMD as measured by the change from Visit 2 for T80/A10 is equal to O40/H25.
FMD [after 26 weeks]
The overall mean improvement following 26 weeks of treatment in FMD as measured by the change from Visit 2 for T80/A10 is equal to O40/H25.

Secondary Outcome Measures

Echogenicity [baseline]
To investigate the effects of T and A vs O and HCTZ on grayscale median of carotid atherosclerotic plaques
arterial stiffness [baseline]
To investigate the effects of T and A vs O and HCTZ in reducing arterial stiffness
arterial stiffness [after 26 weeks]
To investigate the effects of T and A vs O and HCTZ in reducing arterial stiffness
Echogenicity [after 26 weeks]
To investigate the effects of T and A vs O and HCTZ on grayscale median of carotid atherosclerotic plaques

Eligibility Criteria

Criteria

Ages Eligible for Study:

35 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Ability to provide written informed consent in accordance with Good Clinical Practice and local legislation.
Age 35 and older.
Male and female, treated and treatment-naive patients with uncontrolled hypertension (defined as 20/10 mmHg above target BP of <140/90 mmHg [<130/80 mmHg for renally impaired and/ or diabetics patients])
Male and female treated patients with controlled hypertension (defined as target BP < 140/90 mmHg [ < 130/80 mmHg for renally impaired and/ or diabetics patients])
3 cardiovascular risk factors CVRFs and/or metabolic syndrome and/or diabetes mellitus and/or end organ damage

Exclusion Criteria:

Pretreatment with Telmisartan within the last 3 months.
Pretreatment with Amlodipine, Diuretics and AT1Blocker/ACEInhibitor within the last 3 months
Myocardial infarction within last 6 months.
Previous stroke or hemodynamically relevant stenosis of carotic arteria (>70%).
Previous cardial or peripheral bypass surgery within last 6 months.
PAD stadium III - IV n.F.
Chronic heart failure NYHA III- IV.
Unstable angina.
Known intolerance to angiotensin receptor blockers, diuretics or dihydropyridine calcium channel blocker.
Pre-menopausal women (last menstruation ≤1 year prior to signing informed consent) who:
are not surgically sterile; or
are nursing, or
are pregnant, or
are of childbearing potential and are NOT practicing acceptable methods of birth control, or do NOT plan to continue practicing an acceptable method throughout the trial.

The only acceptable methods of birth control are:

Intra-Uterine Device (IUD)
Oral
implantable or injectable contraceptives
Estrogen patch
Hormonal birth control should have been in use for at least three months before the study and continue at least until the next menstrual period after completing the study
Night shift workers who routinely sleep during the daytime and whose work hours include midnight to 4:00 a.m.
Known or suspected secondary hypertension (e.g., renal artery stenosis or phaeochromocytoma)
Mean in-clinic seated cuff SBP ≥180 mmHg and/or DBP ≥110 mmHg
Renal dysfunction as defined by the following laboratory parameters:
Serum creatinine >3.0 mg/dL (or >265 μmol/L) and/or known estimated creatinine clearance of <30 ml/min and/or clinical markers of severe renal impairment.
Bilateral renal artery stenosis, renal artery stenosis in a solitary kidney, post-renal transplant patients or patients with only one kidney
Clinically relevant hypokalemia or hyperkalemia (i.e., <3.0 or >5.5 mEq/L, may be rechecked for suspected error in result)
Uncorrected sodium or volume depletion
Primary aldosteronism
Hereditary fructose intolerance
Biliary obstructive disorders (e.g., cholestasis) or hepatic insufficiency
Clinically significant ventricular tachycardia, atrial fibrillation, atrial flutter or other clinically relevant cardiac arrhythmias as determined by the Investigator
Hypertrophic obstructive cardiomyopathy, severe obstructive coronary artery disease, aortic stenosis, hemodynamically relevant stenosis of the aortic or mitral valve
Patients whose diabetes has not been stable and controlled for at least the past three months as defined by an HbA1C ≥10%
Patients who have previously experienced symptoms characteristic of angioedema during treatment with ACE inhibitors or angiotensin-II receptor antagonists
History of drug or alcohol abuses within six months prior to signing the informed consent form
Concomitant administration of any medications known to affect BP, except medications allowed by the protocol
Any investigational drug therapy within one month of signing the informed consent
Known contraindication to any component of the trial drugs (telmisartan, amlodipine, olmesartan, hydrochlorothiazide)
History of non-compliance or inability to comply with prescribed medications or protocol procedures
Any other clinical condition which, in the opinion of the investigator, would not allow safe completion of the protocol and safe administration of the trial medication