Clinical trial NCT03264352: Intervention for High-normal Blood Pressure in Adults With Type 2 Diabetes
Official title: Intervention for High-normal Blood Pressure in Adults With Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Diabetes Mellitus, Type 2
Adverse Event
Blood Pressure
Prehypertension
Cardiovascular Risk Factor
Lead sponsor: Guangdong Provincial People's Hospital
Sponsor class: OTHER
First posted: 2017-08-29
Enrollment: 11414
Sex: ALL
Minimum age (years): 45
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Lowering of blood pressure (BP) in high-risk hypertensive individuals reduces major adverse cardiovascular and cerebrovascular events. Diabetic patients with hypertension benefit from BP lowering treatment. The present trial, IPAD in brief, is a randomized, open-label, parallel-designed, multicenter study involving nearly 12,000 patients to be recruited and to be followed up for a median of four years. IPAD tests the hypothesis that antihypertensive medications in adults with type 2 diabetes, whose seated BP 120-139 mm Hg systolic and below 90 mm Hg diastolic, results in 20% difference in the incidence of major adverse cardiovascular and cerebrovascular events. During follow-up for participants in the intensive group, the sitting systolic pressure should be decreased to below 120 mm Hg, by titration and combination of the study medications of an angiotensin type-1 receptor blocker Allisartan (240 mg/day), a dihydropyridine calcium-channel blocker (amlodipine 5-10 mg/day), and/or other medications if necessary. For those in the standard group, the sitting systolic pressure should be monitored and controlled below 140 mm Hg.

Detailed description: The IPAD trial is a randomized, open-label, parallel-designed, multicenter study. 11,414 patients will be recruited in three years with a median follow up of four years. IPAD tests the hypothesis that intensive antihypertensive medical therapy in adult patients with type 2 diabetes, whose seated BP ranges from 120 to 139 mm Hg systolic and \< 90 mm Hg diastolic, results in 20% reduction in the incidence of major adverse cardiovascular and cerebrovascular events (the primary endpoint), a composite of stroke, cardiovascular death, nonfatal myocardial infarction (MI), hospitalization for heart failure (HF) and hospitalization for unstable angina. Secondary endpoints of this study include: stroke; cardiovascular death; MI; hospitalization for HF; hospitalization for unstable angina; all-cause mortality; overt albuminuria; worsened renal function (the estimated glomerular filtration rate decreased by \> 30% from baseline); end-stage renal disease; development of diabetic retinopathy that needs interventional operation; peripheral arterial diseases; new on-set atrial fibrillation or flutter; cancer; decline of health-related quality of life. Inclusion criteria for the study include T2DM patients aged between 45 and 79 years within the aforementioned BP ranges. for participants in the intensive group, the sitting systolic BP should decrease to \< 120 mm Hg, using titration and combination of study medications consisting of an angiotensin type-1 receptor blocker Allisartan (240 mg/day) and a dihydropyridine calcium-channel blocker (amlodipine 5-10 mg/day), and/or other medications if necessary.For those in the standard group, the sitting systolic pressure should be monitored and controlled below 140 mm Hg. Across the whole study, 820 primary endpoints are expected to occur. Interim analyses will be carried out on an intention-to-treat basis. At the completion of the trial, both an intention-to-treat and a per-protocol analysis will be performed.

Eligibility criteria: Inclusion Criteria:

* irrespective of sex;
* aged between 45 and 79 years;
* with office-measured seated BP 120-139 mm Hg systolic and below 90 mm Hg diastolic;
* diagnosed of type 2 diabetes mellitus (T2DM), currently on diabetic therapy;
* informed consent provided and long-term follow-up possible

Exclusion Criteria:

* poor control of blood glucose, HbA1c \> 10.0%
* administration of any antihypertensive medications within 1 month;
* a history of hypoglycemic coma / seizure;
* confirmed diagnosis of type 1 diabetes mellitus;
* alanine-aminotransferase (ALT) or aspartate-aminotransferase (AST) over three times the upper limit of normal;
* estimated glomerular filtration rate \< 45 ml/min/1.73m2;
* a history of congestive heart failure with left ventricular ejection fraction \< 40%;
* coronary artery disease requiring RAS blockers for secondary prevention;
* acute on-set of stroke within 6 months prior to randomization;
* a ratio of urinary albumin (in mg/L) to urinary creatinine (in g/L) (ACR) ≥ 300 mg/g;
* known contraindications for the active study medications;
* a history of psychological or mental disorder;
* pregnancy or currently planning to have babies or lactation;
* severe diseases such as severe heart diseases;
* an expected residual life span less than 3 years;
* a malignancy that clinical investigators consider as unsuitable to participate;
* currently participating in another clinical trial.

Primary outcomes:
measure: Composite of Major Adverse Cardiovascular and Cerebrovascular Events
timeFrame: 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 outcomes:
measure: Stroke
timeFrame: From date of randomization until the date of first documented incidence of stroke, assessed up to 60 months.
measure: Cardiovascular Death
timeFrame: From date of randomization until the date of cardiovascular death, assessed up to 60 months.
measure: Acute Myocardial Infarction
timeFrame: From date of randomization until the date of first documented incidence of acute MI, assessed up to 60 months.
measure: Hospitalization of Unstable Angina
timeFrame: From date of randomization until the date of first documented hospitalization of unstable angina, assessed up to 60 months.
measure: Hospitalization of Congestive Heart Failure
timeFrame: From date of randomization until the date of first documented hospitalization of HF, assessed up to 60 months.
measure: All-cause Mortality
timeFrame: From date of randomization until the date of death from any causes, assessed up to 60 months.
measure: Overt Albuminuria
timeFrame: From date of randomization until the date of confirmed development of overt albuminuria, assessed up to 60 months.
measure: Worsened Renal Function
timeFrame: From date of randomization until the date of first documented incidence of this event, assessed up to 60 months.
measure: End-Stage Renal Disease
timeFrame: From date of randomization until the date of documented diagnosis of end-stage renal disease, assessed up to 60 months.
measure: Diabetic Retinopathy Requiring Interventional Operation or Surgery
timeFrame: From date of randomization until the date of first documented interventional or surgical operation for diabetic retinopathy, assessed up to 60 months.
measure: Peripheral Arterial Diseases Requiring Revascularization
timeFrame: From date of randomization until the date of first documented revascularization for peripheral arterial diseases, assessed up to 60 months.
measure: New Atrial Fibrillation or Flutter
timeFrame: From date of randomization until the date of first documented incidence of atrial fibrillation or flutter, assessed up to 60 months.
measure: Decline of Health-related Quality of Life
timeFrame: up to 60 months
measure: Cancer
timeFrame: From date of randomization until the date of first confirmed diagnosis of a cancer of any type, assessed up to 60 months.
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Guangdong General Hospital
state: Guangdong
Study officials:
affiliation: Guangdong Provincial People's Hospital
name: Jiyan Chen, MD
role: PRINCIPAL_INVESTIGATOR
References: