Clinical trial NCT00846365
Conditions: Essential Hypertension
Keywords: Essential Hypertension Hypertensive Blood Pressure, High Vascular Disease Cardiovascular Disease Drug Therapy
Sponsor: Takeda
Start date: 2009-03-01; Completion date: 2010-06-01
Enrollment: 1085 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to determine the efficacy and safety of azilsartan medoxomil combined with chlorthalidone, once daily (QD), in participants with moderate to severe essential hypertension.

Detailed description:
According to the World Health Organization, hypertension is the most common attributable cause of preventable death in developed nations, as uncontrolled hypertension greatly increases the risk of cardiovascular disease, cerebrovascular disease and renal failure. As the population ages, the prevalence of hypertension will continue to increase if broad and effective preventive measures are not implemented. Despite the availability of antihypertensive agents, hypertension remains inadequately controlled; only about one-third of patients continue to maintain control successfully.

Although most antihypertensive agents are effective at the appropriate dose, the majority have side effects that limit their use. As a class, angiotensin II receptor blockers generally are considered more tolerable than other classes of antihypertensive agents. TAK-491 (azilsartan medoxomil) is an angiotensin II receptor blocker being evaluated by Takeda to treat essential hypertension.

Treatments for essential hypertension commonly include use of a thiazide-like diuretic, either alone or as part of combination treatment. Although chlorthalidone was commonly prescribed in the past, its use has widely been replaced with hydrochlorothiazide, presumably due to a lack of available combination products containing chlorthalidone, the assumption that hydrochlorothiazide and chlorthalidone have similar antihypertensive effects and cardiovascular benefits, and the perception that chlorthalidone use is associated with a greater frequency of hypokalemia. However, the frequency of hypokalemia with chlorthalidone use is relatively low in the dose range of 12.5 to 25 mg and these doses have been shown to be associated with potent blood pressure reduction. Several long-term outcomes trials have shown that blood pressure reductions associated with chlorthalidone treatment reduce risk of cardiovascular morbidity and mortality.

Most hypertensive patients require two or more agents to achieve target blood pressure and diuretics are commonly used in combination with other antihypertensive agents.

Participants in this study will be randomized to receive one of 3 possible dosing combinations of azilsartan medoxomil with either chlorthalidone or olmesartan medoxomil-hydrochlorothiazide over 8 weeks. The total duration of the study is approximately 13 weeks. Participants will make a total of 11 visits to the clinic, and will be required to participate in a follow-up telephone call 14 days after last dose of the study drug for adverse event assessment.

Arms: arm 1: (dependant on blood pressure) arm 2: (dependant on blood pressure) arm 3: (dependant on blood pressure)
Interventions: intervention 1: Azilsartan medoxomil and chlorthalidone intervention 2: Azilsartan medoxomil and chlorthalidone intervention 3: Olmesartan medoxomil-hydrochlorothiazide
Intervention descriptions: intervention 1: Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 40 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks. intervention 2: Azilsartan medoxomil 40 mg and chlorthalidone 12.5, mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 80 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks. intervention 3: Olmesartan medoxomil 20 mg/hydrochlorothiazide 12.5 mg, tablets, orally, and Azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to olmesartan medoxomil 40 mg/hydrochlorothiazide 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Protocol documents: