Study to compare the natriuretic effect of telmisartan to placebo in mild-to-moderate
hypertensive patients on a controlled sodium diet as well as to explore the effects of
telmisartan on norepinephrine, plasma renin activity (PRA), plasma aldosterone, urine
potassium, creatinin, chloride, bicarbonate and uric acid excretion. Additionally it was
assessed whether the natriuretic effect disappears after treatment when telmisartan is
stopped. The effects of telmisartan on seated clinic blood pressure and the relationship
between urine sodium loss and decrease in ambulatory blood pressure after the first dose
were assessed descriptively. Assessment of safety was also considered.
Cumulative urine sodium lossChanges in body weight
Changes in plasma norepinephrine
Changes in renin activity
Changes in aldosterone
Changes in urine potassium
Changes in creatinine chloride
Changes in bicarbonate
Changes in uric acid
Cumulative urinary sodium gain during wash-out period
Changes in seated clinic blood pressure
Changes in 24 hour ambulatory Blood Pressure (ABPM) after the first dose of telmisartan
Number of patients with adverse events
Number of patients with abnormal findings in physical examination
Number of patients with abnormal findings in 12-lead electrocardiogram (ECG)
Number of patients with abnormal changes in laboratory parameters
Minimum age: 18 Years.
Maximum age: 65 Years.
Gender(s): Both.
Inclusion Criteria:
- Mild-to-moderate hypertension as defined by a morning mean diastolic blood pressure
from ≥ 90 and ≤ 115 mmHg and a mean systolic blood pressure ≤ 200 mmHg after five
minutes in the seated position at the end of three weeks of placebo run-in treatment
- Male or female patients between 18 and 65 years of age, inclusive. Patients 60 to 65
years of age must have a screening 24-hour urine creatinine clearance rate of ≥ 1
mL/sec
- Ability to provide written informed consent
Exclusion Criteria:
- Pre-menopausal women (last menstruation ≤ one year to start of screening)
- Post-menopausal women (last menstruation > one year from start of screening or have
had a hysterectomy and oophorectomy)
- Who have < three months of stable estrogen replacement therapy at screening
- Who will be on progesterone therapy at any time during the trial
- Known or suspected secondary hypertension
- Hepatic and/or renal dysfunction as defined by the following laboratory parameters:
- ALT (alanine aminotransferase) or AST (aspartate aminotransferase) greater than
two times the upper limit of reference range
- Serum creatinine greater than 2. 3 mg/dL
- Bilateral renal artery stenosis; renal artery stenosis in a solitary kidney;
post-renal transplant
- NYHA (New York Heart Association) functional class CHF (chronic heart failure) III-IV
- Unstable angina, myocardial infarction or cardiac surgery within the preceding three
months
- Stroke within the preceding six months
- PTCA (percutaneous transluminal coronary angioplasty) within the preceding three
months
- History of angioedema
- Sustained ventricular tachycardia, atrial fibrillation, or other clinically relevant
cardiac arrhythmias as determined by the clinical Investigator
- Hypertrophic obstructive cardiomyopathy, aortic stenosis, hemodynamically relevant
stenosis of aortic or mitral valve
- Administration of digoxin or other digitalis-type drugs
- Patients with insulin-dependent and non-insulin-dependent diabetes mellitus
- History of drug or alcohol dependency
- Use of antihypertensive agents such as diuretics, ACE inhibitors, angiotensin II
antagonists, α-blockers, β-blockers, calcium channel antagonists, direct vasodilators
at any time during the trial
- Administration of other non-antihypertensive medications known to affect blood
pressure (e. g., oral corticosteroids, MAO (monoamine oxidase) inhibitors, nitrates)
at any time during the trial
- Chronic administration of high doses of NSAIDS and aspirin (e. g., ibuprofen for
rheumatoid arthritis and osteoarthritis in total daily dose in excess of 1600 mg,
aspirin in excess of 2 Gm per day)
- Chronic use of salt substitutes containing potassium chloride; potassium supplements;
extreme dietary restrictions
- Clinically significant sodium depletion as defined by a serum sodium level less than
130 mEq/L
- Clinically significant hyperkalemia as defined by a serum potassium level greater
than 6. 0 mEq/L. Clinically significant hypokalemia as defined by a serum potassium
level less than 3. 0 mEq/L
- Patients receiving any investigational therapy within one month of signing the
informed consent form. Note that patients who have participated in previous
telmisartan studies may participate in this study provided there has been at least
one month between discontinuing the previous study and signing the consent for the
present study
- Known hypersensitivity to any component of telmisartan
- 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