The primary objective of the SMOOTH study was to demonstrate that, when combined with hydrochlorothiazide (12.5 mg), telmisartan (80 mg) is at least as effective and possibly superior to valsartan (160 mg) in lowering systolic and diastolic BP during the last 6 hours of the 24-hour dosing interval (i.e., the critical morning period) following a 10-week treatment period in hypertensive, overweight/obese Type-2 diabetics.
Prospective, Randomized, Open-Label, Blinded Endpoint, Forced Titration Study to Compare Telmisartan Combined With HCTZ (80mg/12.5mg), to Valsartan Combined With HCTZ (160mg/12.5mg), for the Control of Mild-to-Moderate Hypertension in Obese Patients With Type 2 Diabetes Mellitus Using ABPM.
Hypertension, Diabetes Mellitus (Type 2)
Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
Primary Outcome Measures:
- Changes following treatment in blood pressure during the last 6 hours of the 24-hour dosing interval as measured by automated blood pressure monitor.
Secondary Outcome Measures:
- Various secondary outcomes related to 1) automated blood pressure monitoring; 2) in-clinic seated trough measurements and blood pressure-related response rates.
January 2003; Study completion: December 2004
Eligibility & Criteria
- Ages Eligible for Study: 30 Years and above
- Genders Eligible for Study: Both
- Ability to provide written informed consent.
- Hypertension defined as a mean seated DBP of 95-109 (inclusive) mmHg, and/or SBP of 140-179 (inclusive) mmHg, measured by BpTRU electronic or manual cuff at Visit 2.
- 24-hour mean DBP of >= 85 mmHg, and/or SBP = 130 mmHg, measured by ABPM at Visit 3.
- 30 years of age or greater.
- Ability to stop current antihypertensive therapy and other disallowed medications without risk to the patient.
- Diagnosis of type-2 diabetes mellitus with HbA1C less than or equal to 10%.
- Overweight or obese as defined by a BMI >= 27 kg/m2 in non-Asians and >= 24 kg/m2 in Asians.
- Negative UPT for females.
- Pre-menopausal women, not surgically sterile or, not nursing/pregnant or are of child-bearing potential and will not practice acceptable methods of birth control during study.
- Night shift workers
- Mean sitting SBP >= 180 mmHg or mean sitting DBP >= 110 mmHg during any visit of the placebo run-in period.
- Known or suspected secondary hypertension. Hepatic and/or renal dysfunction
- Fasting serum glucose > 17 mmol/l (or 300mg/dl) at visit 2
- Bilateral renal artery stenosis, renal artery stenosis in a solitary kidney, patients on dialysis or post-renal transplant patients.
- Clinically relevant sodium depletion, hypokalaemia or hyperkalaemia.
- Uncorrected volume depletion.
- Primary aldosteronism.
- Hereditary fructose intolerance.
- Biliary obstructive disorders (e.g. cholestasis).
- Congestive heart failure
- Stroke within the past six months.
- Documented severe obstructive coronary artery disease.
- Myocardial infarction, cardiac surgery or unstable angina within the past three months.
- PCI (percutaneous coronary intervention) within the past three months or planned during trial period.
- Sustained ventricular tachycardia, atrial fibrillation, atrial flutter or other clinically relevant cardiac arrhythmias.
- Hypertrophic obstructive cardiomyopathy, aortic stenosis, hemodynamically relevant stenosis of the aortic or mitral valve.
- Patients with type-1 diabetes mellitus.
- Patients who have previously experienced symptoms of angioedema during ACE or ARB treatment.
- History of drug or alcohol dependency in past six months.
- Chronic administration of any medications known to affect blood pressure, except medication allowed by the protocol.
- Any investigational drug therapy within the past month.
- Known hypersensitivity to any component of the study drug.
- Concurrent use of corticosteroids, colestipol or cholestyramine resins.
- Any clinical condition which would not allow safe completion of the protocol.
- Inability to comply with the protocol.
- Any surgery that is, at the time of screening, planned to take place during the study period.
- History of non-compliance with prescribed medications.
- Kippa-Ring, Queensland, 4021, Australia
- Prahran, Victoria, 3181, Australia
- Malvern, Victoria, 3144, Australia