Clinical trial NCT04978649: Intervention for High-normal Blood Pressure in Adults With Type 2 Diabetes-----renal Substudy
Official title: Intervention for High-normal Blood Pressure in Adults With Type 2 Diabetes-----renal Substudy
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Diabetes Mellitus, Type 2
Blood Pressure
Keywords: prehypertension
renal disease
Lead sponsor: Guangdong Provincial People's Hospital
Sponsor class: OTHER
First posted: 2021-07-27
Enrollment: 0
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 (CV) and renal events. Diabetic patients with hypertension benefit from BP lowering treatment. The present trial, IPAD-CKD in brief, is a randomized, open-label, parallel-designed, multicenter study involving nearly 5322 patients to be recruited over three years and to be followed up for a median of four years and a half. IPAD-CKD 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 renal 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 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/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-CKD trial is a randomized, open-label, parallel-designed, multicenter study. 5322 patients will be recruited over three years with a median follow up of 4.5 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 renal events (the primary endpoint), a composite of renal failure and proteinuria progression. Secondary endpoints of this study include: renal failure ; proteinuria progression; proteinuria reversion; end stage renal disease; cardiovascular-cause mortality; MI; hospitalization for HF; stroke;hospitalization for unstable angina; all-cause mortality;development of diabetic retinopathy that needs interventional operation; peripheral arterial diseases; new on-set atrial fibrillation or flutter; cancer.

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, 310 primary endpoints are expected to occur. Interim analyses will be carried out on an intention-to-treat basis at the accumulation of 107 and 214 primary endpoints respectively. 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; a glycosylated hemoglobin (HbA1c) ≤ 8.5%;
* informed consent provided and long-term follow-up possible

Exclusion Criteria:

* 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%, requiring treatment with renin-angiotensin system (RAS) blockers; 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;
* a history of primary or secondary renal diesease requiring a therapy using glucocorticoid or immunity inhibitor;
* a history of polycystic kidney;
* 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 valvular 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 Renal Events
timeFrame: From date of randomization until the date of first documented incidence of the major renal events prespecified, whichever comes first, assessed up to 60 months
Secondary outcomes:
measure: renal failure
timeFrame: From date of randomization until the date of first documented incidence of the major renal events prespecified, whichever comes first, assessed up to 60 months
measure: proteinuria progression
timeFrame: From date of randomization until the date of first documented incidence of the major renal events prespecified, whichever comes first, assessed up to 60 months
measure: proteinuria reversion
timeFrame: From date of randomization until the date of first documented incidence of the major renal events prespecified, whichever comes first, assessed up to 60 months
measure: cardiovascular-cause mortality
timeFrame: From date of randomization until the date of first documented incidence of the major renal events prespecified, whichever comes first, assessed up to 60 months
measure: Acute Myocardial Infarction
timeFrame: From date of randomization until the date of first documented incidence of the major renal events prespecified, whichever comes first, assessed up to 60 months
measure: Hospitalization of Congestive Heart Failure
timeFrame: From date of randomization until the date of first documented incidence of the major renal events prespecified, whichever comes first, assessed up to 60 months
measure: Hospitalization of Unstable Angina
timeFrame: From date of randomization until the date of first documented incidence of the major renal events prespecified, whichever comes first, assessed up to 60 months
measure: All-cause Mortality
timeFrame: Time Frame: From date of randomization until the date of death from any causes, assessed up to 60 months.
measure: Diabetic Retinopathy Requiring Interventional Operation or Surgery
timeFrame: Time Frame: From date of randomization until the date of death from any causes, assessed up to 60 months.
measure: Peripheral Arterial Diseases Requiring Revascularization
timeFrame: Time Frame: From date of randomization until the date of death from any causes, assessed up to 60 months.
measure: New Atrial Fibrillation or Flutter
timeFrame: Time Frame: From date of randomization until the date of death from any causes, assessed up to 60 months.
measure: Cancer
timeFrame: Time Frame: From date of randomization until the date of death from any causes, assessed up to 60 months.
Other outcomes:
Locations:
Study officials:
affiliation: Guangdong Provincial People's Hospital
name: Xueqing Yu, Doctor
role: STUDY_CHAIR
References: