Intervention for High-normal Blood Pressure in Adults With Type 2 Diabetes-----renal Substudy

NCT ID: NCT04978649

Last Updated: 2022-08-26

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE4
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-01
• Study Completion Date: 2028-07-31

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.

Conditions

Diabetes Mellitus, Type 2; Blood Pressure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

intensive treatment group

Real antihypertensive agents will be provided for this arm, to decrease systolic BP to lower than 120 mm Hg. In this 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). Treatment will be started with Allisartan 240 mg. If necessary to reach the BP goal, Amlodipine (first 5 mg or then 10 mg daily) will be given in addition. If intolerable side effects occur, first-line medication may be replaced by second-line medication.

Group Type: ACTIVE_COMPARATOR

Allisartan Isoproxil

Intervention Type: DRUG

Allisartan Isoproxil 240mg daily will be used to lower BP to below 120 mm Hg systolic.

Amlodipine

Intervention Type: DRUG

Amlodipine 5mg daily will be added to Allisartan Isoproxil and afterwards increased to 10mg daily, if necessary to reach the blood pressure goal (below 120 mm Hg systolic).

standard treatment group

In this arm participants are followed up and no medications be used until BP becomes ≥ 140 mm Hg systolic and/or 90 mm Hg diastolic. Medications are determined by investigators in lines with recommendations by current Chinese guidelines to decrease BP to lower than 140 mm Hg systolic and to lower than 90 mm Hg diastolic.

Group Type: PLACEBO_COMPARATOR

Allisartan Isoproxil

Intervention Type: DRUG

Allisartan Isoproxil 240mg daily will be used to lower BP to below 120 mm Hg systolic.

Amlodipine

Intervention Type: DRUG

Amlodipine 5mg daily will be added to Allisartan Isoproxil and afterwards increased to 10mg daily, if necessary to reach the blood pressure goal (below 120 mm Hg systolic).

Interventions

Allisartan Isoproxil

Allisartan Isoproxil 240mg daily will be used to lower BP to below 120 mm Hg systolic.

Intervention Type: DRUG

Amlodipine

Amlodipine 5mg daily will be added to Allisartan Isoproxil and afterwards increased to 10mg daily, if necessary to reach the blood pressure goal (below 120 mm Hg systolic).

Intervention Type: DRUG

Other Intervention Names

Xinlitan; Qiaohean

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.

• Minimum Eligible Age: 45 Years
• Maximum Eligible Age: 79 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Guangdong Provincial People's Hospital

OTHER

Sponsor Role: lead

Responsible Party

XueQing Yu

Dean

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Xueqing Yu, Doctor

Role: STUDY_CHAIR

Guangdong Provincial People's Hospital

Other Identifiers

GDPH-IPAD-CKD

Identifier Type: -

Identifier Source: org_study_id