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

NCT03264352 | Recruiting Phase 4 DMC

• 1 other identifier: GDREC2017192H
• Study Type: interventional
• Target: 11,414
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetes Mellitus, Type 2; Adverse Event; Blood Pressure; Prehypertension; Cardiovascular Risk Factor

Outcome Measures

Primary Outcomes (1)

• Composite of Major Adverse Cardiovascular and Cerebrovascular Events

  The major adverse cardiovascular and cerebrovascular events defined in the study include cardiovascular death, nonfatal stroke, nonfatal myocardial infarction, hospitalization for congestive heart failure and hospitalization for unstable angina.

  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 (14)

• Stroke

  From date of randomization until the date of first documented incidence of stroke, assessed up to 60 months.

• Cardiovascular Death

  From date of randomization until the date of cardiovascular death, assessed up to 60 months.

• Acute Myocardial Infarction

  From date of randomization until the date of first documented incidence of acute MI, assessed up to 60 months.

• Hospitalization of Unstable Angina

  From date of randomization until the date of first documented hospitalization of unstable angina, assessed up to 60 months.

• Hospitalization of Congestive Heart Failure

  From date of randomization until the date of first documented hospitalization of HF, 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 5mg

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.

Other: Standard treatment by current guideline

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

Amlodipine 5mg 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 by current guideline OTHER

No BP-lowering medications are 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.

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;
• informed consent provided and long-term follow-up possible

You may not qualify if:

• 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;

Sponsors & Collaborators

• XueQing Yu: lead

Study Sites (1)

Guangdong General Hospital

Guangzhou, Guangdong, 501080, China

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Prehypertension

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Jiyan Chen, MD

  Guangdong Provincial People's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jiyan Chen, MD

CONTACT

86-13802911148; chen-jiyan@163.com

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: SPONSOR INVESTIGATOR
• PI Title: Director of the Guangdong Provincial People's Hospital

Study Record Dates

• First Submitted: August 21, 2017
• First Posted: August 29, 2017
• Study Start: February 1, 2018
• Primary Completion: September 1, 2025
• Study Completion: September 1, 2025
• Last Updated: March 12, 2025

Record last verified: 2025-03

Locations

CN (1)