The primary objective of this trial is to compare the efficacy and safety of telmisartan 40mg / hydrochlorothiazide 12.5mg (Micardis Plus) with that of losartan 50mg / hydrochlorothiazide 12.5mg, a reference AIIA combined with diuretic, in Taiwanese patients with mild to moderate hypertension.

Condition	Intervention	Phase
Hypertension	Drug: telmisartan 40mg / hydrochlorothiazide 12.5mg  Drug: losartan 50mg / hydrochlorothiazide 12.5mg	Phase III

Further Study Details: 

Primary Outcomes: Change from baseline in sitting diastolic blood pressure (DBP) at trough (24 hours post-dosing) at the last observation during the double-blind phase.
Secondary Outcomes: Change from baseline in sitting SBP, standing DBP, standing SBP, sitting and standing heart rate at trough as well as blood pressure control and blood pressure response as defined in study protocol at the last observation will be evaluated.
Expected Total Enrollment:  40

This is a randomised, double-blind, double-dummy, parallel-group study in mild to moderate hypertensive patients treated for eight weeks with either telmisartan 40mg / hydrochlorothiazide 12.5mg or losartan 50mg/ hydrochlorothiazide 12.5mg.

The study will be divided into two phases:

(i) Placebo Run-in Phase (Visit 1 to Visit 2, day -14 (~ day -21) to day 1): Initial screening and withdrawal of current anti-hypertensives is followed by a two week placebo phase with dummy telmisartan 40mg / hydrochlorothiazide 12.5mg and dummy losartan 50mg / hydrochlorothiazide 12.5mg. Baseline assessments are done at the end of the 2 week run-in phase (at Visit 2, day 1).

(ii) Treatment Phase (Visit 2 to 4, day 1 to day 57): This is an eight-weeks double-blind, double-dummy parallel trial with telmisartan 40mg / hydrochlorothiazide 12.5mg or losartan 50mg / hydrochlorothiazide 12.5mg. Final assessments are done at the end of the eight-weeks treatment phase at Visit 4.

Study Hypothesis:

Null and alternative hypothesis The change from baseline in sitting diastolic blood pressure at trough (24 hours post-dosing) at the last visit during the double-blind phase defines the primary endpoint. This trial is to test the non-inferiority of efficacy of telmisartan 40mg / hydrochlorothiazide 12.5mg to losartan 50mg / hydrochlorothiazide 12.5mg. A difference of 3mmHg in reducing sitting diastolic blood pressure would be considered clinically significant.

H0: (Reduction from baseline in sitting diastolic blood pressure at trough of losartan 50mg / hydroclorothiazide 12.5mg group) – (Reduction from baseline in sitting diastolic blood pressure at trough of telmisartan 40mg / hydrochlorothiazide 12.5mg group) > 3 mmHg HA: (Reduction from baseline in sitting diastolic blood pressure at trough of losartan 50mg / hydroclorothiazide 12.5mg group) – (Reduction from baseline in sitting diastolic blood pressure at trough of telmisartan 40mg / hydrochlorothiazide 12.5mg group) ≦ 3 mmHg

Comparison(s):

Change from baseline in sitting diastolic blood pressure (DBP) at trough (24 hours post-dosing) at the last observation during the double-blind phase.

A 24-hour post-dose timepoint at the last visit of the run-in phase will be specified as the baseline trough measurement.

Ages Eligible for Study:  20 Years   -   80 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria

1. Mild to moderate hypertension as defined by a morning mean ( > 95 and < 115 mmHg) of two diastolic blood pressure measurements (DBP) after 5 min in the sitting position following a minimum 2-week placebo run in phase. Mean sitting systolic blood pressure (SBP) must be > 140 and < 200 mmHg. The mean DBP and SBP values are calculated as the mean of the two sitting measurements taken 2 min apart just before the drug intake.
2. Male or female between 20 to 80 years of age.
3. Ability to provide written informed consent.

Exclusion Criteria

1. Patients are still taking more than three anti-hypertensives at the screening visit.

2. Pre-menopausal women (last menstruation < one year prior to start of run-in phase). Who have a positive serum pregnancy test at baseline; and/or who are nursing; who are of child-bearing potential and are:

   • NOT practicing acceptable means of birth control (this includes oral, implantable or injectable contraceptives and intrauterine devices
   • do NOT plan to continue using this method throughout the study and for two weeks after the last dose of study medication has been taken and
   • do NOT agree to submit to periodic pregnancy testing during the trial
3. Known or suspected secondary hypertension.
4. Mean sitting DBP < 95 mmHg and/or mean sitting SBP > 200 mmHg at the end of placebo run-in phase.

5. Hepatic and/or renal dysfunction as defined by the following laboratory parameters:

   1. SGPT (ALT) or SGOT (AST) > two times upper the limit of normal range
   2. Serum creatinine > 2.3 mg/dl
6. Known bilateral renal artery stenosis, patient with a solitary kidney, post renal transplant.
7. Known NYHA functional class Chronic Heart Failure (CHF) III, IV.
8. Unstable angina, myocardial infarction, cardiac surgery or stroke within the preceding six months.
9. Post-Transluminal Coronary Angioplasty (PTCA) within the preceding three months.
10. Sustained ventricular tachycardia, atrial fibrillation, second or third degree AV block, VPC or APC ( > 10% of heart rate) or other clinically relevant cardiac arrhythmia as determined by the clinical investigator.
11. Hypertrophic obstructive cardiomyopathy, aortic stenosis, hemodynamically relevant stenosis of aortic or mitral valve.
12. Once documented evidence by ophthalmological examination of significant retinal haemorrhages/exudates.
13. Clinically significant sodium depletion as defined by serum sodium level less than 130 mmol/L.
14. Clinically significant hyperkalemia as defined by serum potassium level > 5.5 mmol/L.
15. Non-insulin dependent diabetes mellitus poorly controlled which is defined as HbA1c > 8% twice consecutively within 6 months and/or AC blood sugar > 180mg/dl. (Therapy must be stabilized for at least one month prior to starting the run-in phase)
16. Insulin Dependent Diabetes Mellitus.
17. Chronic (more than 3 consecutive days) administration of oral anticoagulants (such as, warfarin) and/or digoxin within the past 6 months.
18. Known drug or alcohol dependency.
19. Administration of medications known to affect blood pressure, except medication allowed by the protocol. (see section 4.6)
20. Angioedema with ACE inhibitors.
21. Use of nitrates.
22. Chronic use of salt substitutes containing potassium chloride, extreme dietary restrictions.
23. Patients treated by lithium, neuroleptics and/or imipramine group antidepressants.
24. Patients receiving any investigational therapy within one month prior to signing the informed consent.
25. Known hypersensitivity to any component of the formulation.
26. Any other clinical condition which, in the opinion of the principal investigator, would not allow safe completion of the protocol and safe administration of trial medication.

Taiwan
      Machay Memorial Hospital, Taipei,  104,  Taiwan

Study chairs or principal investigators

Cynthia Lin, Ms,  Study Chair,  B.I. Taiwan Ltd.   

Study ID Numbers:  502.406
Last Updated:  August 22, 2005
Record first received:  August 22, 2005
ClinicalTrials.gov Identifier:  NCT00133185
Health Authority: Taiwan: Department of Health
ClinicalTrials.gov processed this record on 2005-08-23