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

NCT04978649 | Withdrawn Phase 4 DMC

• 1 other identifier: GDPH-IPAD-CKD
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Diabetes Mellitus, Type 2; Blood Pressure

Keywords

prehypertension; renal disease

Outcome Measures

Primary Outcomes (1)

• Composite of Major Renal Events

  The major renal events defined in the study include a composite of renal failure (defined as dialysis, transplantation, or a sustained estimated GFR of \<15 ml per minute per 1.73 m 2), or serum creatinine level \>3.3 mg/dl, or a doubling of the serum creatinine level）and proteinuria progression（defined as:uACR ≥30 mg/gCr if baseline uACR\< 30 mg/gCr; uACR ≥300 mg/gCr if baseline uACR is between 30 to 300 mg/gCr. ）

  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 (12)

• renal failure

  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

• proteinuria progression

  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

• proteinuria reversion

  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

• cardiovascular-cause mortality

  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

• Acute Myocardial Infarction

  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

Study Arms (2)

intensive treatment group

ACTIVE COMPARATOR

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.

Drug: Allisartan Isoproxil; Drug: Amlodipine

standard treatment group

PLACEBO COMPARATOR

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.

Drug: Allisartan Isoproxil; Drug: Amlodipine

Interventions

Allisartan Isoproxil DRUG

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

Also known as: Xinlitan

intensive treatment group; standard treatment group

Amlodipine 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).

Also known as: Qiaohean

intensive treatment group; standard treatment group

Eligibility Criteria

• Age: 45 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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;

Sponsors & Collaborators

• Guangdong Provincial People's Hospital: lead

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Prehypertension; Kidney Diseases

Interventions

allisartan isoproxil; Amlodipine

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Vascular Diseases; Cardiovascular Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Xueqing Yu, Doctor

  Guangdong Provincial People's Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dean

Study Record Dates

• First Submitted: July 20, 2021
• First Posted: July 27, 2021
• Study Start: September 1, 2021
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): July 31, 2028
• Last Updated: August 26, 2022

Record last verified: 2022-08