Intervention for High-normal or Borderline-elevated Blood Pressure in Adults With Type 2 Diabetes "IPAD"

Not yet recruiting

Phase 4 Results N/A

Trial Description

Lowering of blood pressure (BP) in high-risk hypertensive individuals reduces major adverse cardiovascular (CV) events. Diabetic patients with hypertension benefit from BP lowering treatment. The present trial,IPAD in brief, is a randomized, double-blind, placebo-controlled, parallel-group, multicenter study involving 12,000 patients to be recruited over three years and to be followed up for a median of three years and a half. IPAD tests the hypothesis that antihypertensive medications in adults with type 2 diabetes, whose seated BP 130-149 mm Hg systolic and below 90 mm Hg diastolic, results in 35% difference in the incidence of stroke. During follow-up the sitting systolic pressure should be decreased both by at least 10 mm Hg and lower than 130 mm Hg, by titration and combination of the double-blind study medications of an angiotensin type-1 receptor blocker Allisartan (240 mg/day), a dihydropyridine calcium-channel blocker (amlodipine 5-10 mg/day), and a hydrochlorothiazide (12.5-25 mg/day). In the placebo group, identical tablets will be used similarly.

Detailed Description

The IPAD trial is a randomized, double-blind, placebo-controlled, multicenter study. 12,000 patients will be recruited over three years with a median follow up of 3.5 years. IPAD tests the hypothesis that antihypertensive medical therapy in adult patients with type 2 diabetes, whose seated BP ranges from 130 to 149 mm Hg systolic and ≤ 90 mm Hg diastolic, results in 35% reduction in the incidence of stroke, which is the primary endpoint. Secondary endpoints of this study include: a composite of cardiovascular death, nonfatal stroke, nonfatal MI, hospitalization for heart failure and hospitalization for unstable angina; each single event listed above; all-cause mortality; renal dysfunction; diabetic retinopathy that needs interventional operation; peripheral arterial diseases; new on-set atrial fibrillation or flutter; cancer; change of health-related quality of life; cost-effectiveness of medications. Inclusion criteria for the study include T2DM patients aged between 35 and 75 years within the aforementioned BP ranges. The sitting systolic BP should decrease by at least 10 mm Hg systolic and to ≤130 mm Hg, using titration and combination of the double-blind study medications consisting of an angiotensin type-1 receptor blocker Allisartan (240 mg/day), a dihydropyridine calcium-channel blocker (amlodipine 5-10 mg/day), and a hydrochlorothiazide (12.5-25 mg/day). In the control group, placebo tablets will be used. Across the whole study, 282 primary endpoints are expected to occur. Interim analyses will be carried out on an intention-to-treat basis at the accumulation of every 100 primary endpoints. At the completion of the trial, both an intention-to-treat and a per-protocol analysis will be performed.

Conditions

Interventions

  • Allisartan Isoproxil Drug
    Other Names: Xinlitan
    Intervention Desc: Allisartan Isoproxil 240mg daily will be used.
    ARM 1: Kind: Experimental
    Label: active-treatment group
    Description: Real antihypertensive agents will be provided for this arm, to decrease systolic BP both by at least 10 mm Hg and lower than 130 mm Hg. In the active-treatment group, the following study medications will be used: tablets with Allisartan Isoproxil 240 mg (first-line medication); tablets with Amlodipine 5 mg (second-line medication); scored tablets with hydrochlorothiazide 25 mg (third-line medication). Treatment will be started with Allisartan 240 mg. If necessary to reach the BP goal, Amlodipine (first 5 mg or then 10 mg daily) and afterwards hydrochlorothiazide (first 12.5 mg or then 25 mg daily) will be given in addition. If intolerable side effects occur, first-line medication may be replaced by second-line or similarly, second-line medication may be replaced by third-line medication.
  • Amlodipine 5mg Drug
    Other Names: Qiaohean
    Intervention Desc: Amlodipine 5mg daily will be added to Allisartan Isoproxil and afterwards increased to 10mg daily, if necessary to reach the blood pressure goal,
    ARM 1: Kind: Experimental
    Label: active-treatment group
    Description: Real antihypertensive agents will be provided for this arm, to decrease systolic BP both by at least 10 mm Hg and lower than 130 mm Hg. In the active-treatment group, the following study medications will be used: tablets with Allisartan Isoproxil 240 mg (first-line medication); tablets with Amlodipine 5 mg (second-line medication); scored tablets with hydrochlorothiazide 25 mg (third-line medication). Treatment will be started with Allisartan 240 mg. If necessary to reach the BP goal, Amlodipine (first 5 mg or then 10 mg daily) and afterwards hydrochlorothiazide (first 12.5 mg or then 25 mg daily) will be given in addition. If intolerable side effects occur, first-line medication may be replaced by second-line or similarly, second-line medication may be replaced by third-line medication.
  • Hydrochlorothiazide 25 mg Drug
    Intervention Desc: Hydrochlorothiazide 25 mg (first 12.5 mg or then 25 mg daily) will be given subsequently if the blood pressure goal is still not reached.
    ARM 1: Kind: Experimental
    Label: active-treatment group
    Description: Real antihypertensive agents will be provided for this arm, to decrease systolic BP both by at least 10 mm Hg and lower than 130 mm Hg. In the active-treatment group, the following study medications will be used: tablets with Allisartan Isoproxil 240 mg (first-line medication); tablets with Amlodipine 5 mg (second-line medication); scored tablets with hydrochlorothiazide 25 mg (third-line medication). Treatment will be started with Allisartan 240 mg. If necessary to reach the BP goal, Amlodipine (first 5 mg or then 10 mg daily) and afterwards hydrochlorothiazide (first 12.5 mg or then 25 mg daily) will be given in addition. If intolerable side effects occur, first-line medication may be replaced by second-line or similarly, second-line medication may be replaced by third-line medication.
  • Allisartan Isoproxil placebo Drug
    Intervention Desc: Allisartan Isoproxil placebo is identical to Allisartan Isoproxil 240mg.
    ARM 1: Kind: Experimental
    Label: placebo group
    Description: This arm receives identical agents to the active study drugs (Allisartan Isoproxil placebo, Amlodipine placebo and hydrochlorothiazide placebo) also to decrease systolic BP both by at least 10 mm Hg and lower than 130 mm Hg, with a similar schedule of administration to the parallel arm.
  • Amlodipine placebo Drug
    Intervention Desc: Amlodipine 5mg placebo is identical to Amlodipine 5mg.
    ARM 1: Kind: Experimental
    Label: placebo group
    Description: This arm receives identical agents to the active study drugs (Allisartan Isoproxil placebo, Amlodipine placebo and hydrochlorothiazide placebo) also to decrease systolic BP both by at least 10 mm Hg and lower than 130 mm Hg, with a similar schedule of administration to the parallel arm.
  • Hydrochlorothiazide placebo Drug
    Intervention Desc: Hydrochlorothiazide 25mg placebo is identical to Hydrochlorothiazide 25mg.
    ARM 1: Kind: Experimental
    Label: placebo group
    Description: This arm receives identical agents to the active study drugs (Allisartan Isoproxil placebo, Amlodipine placebo and hydrochlorothiazide placebo) also to decrease systolic BP both by at least 10 mm Hg and lower than 130 mm Hg, with a similar schedule of administration to the parallel arm.

Outcomes

Type Measure Time Frame Safety Issue
Primary Stroke From date of randomization until the date of first documented incidence of stroke, assessed up to 60 months.
Secondary Composite of Major Adverse Cardiovascular Events From date of randomization until the date of first documented incidence of the major adverse cardiovascular events prespecified, whichever comes first, assessed up to 60 months
Secondary Cardiovascular Death From date of randomization until the date of cardiovascular death, assessed up to 60 months.
Secondary Acute Myocardial Infarction From date of randomization until the date of first documented incidence of acute MI, assessed up to 60 months.
Secondary Hospitalization of Unstable Angina From date of randomization until the date of first documented hospitalization of unstable angina, assessed up to 60 months.
Secondary Hospitalization of Congestive Heart Failure From date of randomization until the date of first documented hospitalization of HF, assessed up to 60 months.
Secondary All-cause Mortality From date of randomization until the date of death from any causes, assessed up to 60 months.
Secondary Overt Albuminuria From date of randomization until the date of confirmed development of overt albuminuria, assessed up to 60 months.
Secondary End-Stage Renal Disease From date of randomization until the date of documented diagnosis of end-stage renal disease, assessed up to 60 months.
Secondary Diabetic Retinopathy Requiring Interventional Operation or Surgery From date of randomization until the date of first documented interventional or surgical operation for diabetic retinopathy, assessed up to 60 months.
Secondary Peripheral Arterial Diseases Requiring Revascularization From date of randomization until the date of first documented revascularization for peripheral arterial diseases, assessed up to 60 months.
Secondary New Atrial Fibrillation or Flutter From date of randomization until the date of first documented incidence of atrial fibrillation or flutter, assessed up to 60 months.
Secondary Cancer From date of randomization until the date of first confirmed diagnosis of a cancer of any type, assessed up to 60 months.
Secondary Health-related Quality of Life up to 60 months
Secondary Cost-effectiveness of Drug Therapy up to 60 months

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