Telmisartan, Amlodipine and Flow Mediated Dilation

Hypertension Clinical Trial

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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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01180205
• Other study ID #: 2009-017010-68
• Status: Active, not recruiting
• Phase: Phase 4
• First received: August 4, 2010
• Last updated: July 11, 2011
• Start date: August 2010
• Est. completion date: October 2011

Study information

• Verified date: April 2010
• Source: Johannes Gutenberg University Mainz
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Ethics CommissionGermany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

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and amlodipine or olmesartan and hydrochlorothiazide starts, so that no medication is stopped without having been replaced by the study medication.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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 576
• Est. completion date: October 2011
• Est. primary completion date: October 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 35 Years and older

Eligibility

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:

1. Pretreatment with Telmisartan within the last 3 months.

2. Pretreatment with Amlodipine, Diuretics and AT1Blocker/ACEInhibitor within the last 3 months

3. Myocardial infarction within last 6 months.

4. Previous stroke or hemodynamically relevant stenosis of carotic arteria (>70%).

5. Previous cardial or peripheral bypass surgery within last 6 months.

6. PAD stadium III - IV n.F.

7. Chronic heart failure NYHA III- IV.

8. Unstable angina.

9. Known intolerance to angiotensin receptor blockers, diuretics or dihydropyridine calcium channel blocker.

10. Pre-menopausal women (last menstruation =1 year prior to signing informed consent) who:

1. are not surgically sterile; or

2. are nursing, or

3. are pregnant, or

4. 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:

5. Intra-Uterine Device (IUD)

6. Oral

7. implantable or injectable contraceptives

8. Estrogen patch

9. 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

11. Night shift workers who routinely sleep during the daytime and whose work hours include midnight to 4:00 a.m.

12. Known or suspected secondary hypertension (e.g., renal artery stenosis or phaeochromocytoma)

13. Mean in-clinic seated cuff SBP =180 mmHg and/or DBP =110 mmHg

14. Renal dysfunction as defined by the following laboratory parameters:

15. 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.

16. Bilateral renal artery stenosis, renal artery stenosis in a solitary kidney, post-renal transplant patients or patients with only one kidney

17. Clinically relevant hypokalemia or hyperkalemia (i.e., <3.0 or >5.5 mEq/L, may be rechecked for suspected error in result)

18. Uncorrected sodium or volume depletion

19. Primary aldosteronism

20. Hereditary fructose intolerance

21. Biliary obstructive disorders (e.g., cholestasis) or hepatic insufficiency

22. Clinically significant ventricular tachycardia, atrial fibrillation, atrial flutter or other clinically relevant cardiac arrhythmias as determined by the Investigator

23. Hypertrophic obstructive cardiomyopathy, severe obstructive coronary artery disease, aortic stenosis, hemodynamically relevant stenosis of the aortic or mitral valve

24. Patients whose diabetes has not been stable and controlled for at least the past three months as defined by an HbA1C =10%

25. Patients who have previously experienced symptoms characteristic of angioedema during treatment with ACE inhibitors or angiotensin-II receptor antagonists

26. History of drug or alcohol abuses within six months prior to signing the informed consent form

27. Concomitant administration of any medications known to affect BP, except medications allowed by the protocol

28. Any investigational drug therapy within one month of signing the informed consent

29. Known contraindication to any component of the trial drugs (telmisartan, amlodipine, olmesartan, hydrochlorothiazide)

30. History of non-compliance or inability to comply with prescribed medications or protocol procedures

31. 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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypertension

Intervention

Drug:
• Telmisartan
Telmisartan (80 mg ,Tablets, QD, p.o., 26 weeks)
• Amlodipine
Amlodpine 5 mg po 14 days, the forced - titration to 10 mg po for 24 weeks
• Olmesartan medoxomil
Olmesartan 40 mg po for 26 weeks
• Hydrochlorothiazide
HCT 12,5 mg po for 14 days, then 25 mg po for 24 weeks

Locations

Country	Name	City	State
Germany	Universitätsmedizin Mainz	Mainz	Rheinland-Pfalz

Sponsors (1)

Lead Sponsor	Collaborator
Johannes Gutenberg University Mainz

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	FMD flow mediated dilation	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.	baseline	No
Primary	FMD	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.	after 26 weeks	No
Secondary	Echogenicity	To investigate the effects of T and A vs O and HCTZ on grayscale median of carotid atherosclerotic plaques	baseline	No
Secondary	arterial stiffness	To investigate the effects of T and A vs O and HCTZ in reducing arterial stiffness	baseline	No
Secondary	arterial stiffness	To investigate the effects of T and A vs O and HCTZ in reducing arterial stiffness	after 26 weeks	No
Secondary	Echogenicity	To investigate the effects of T and A vs O and HCTZ on grayscale median of carotid atherosclerotic plaques	after 26 weeks	No