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

March 10, 2025 updated by: XueQing Yu
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
11414

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 501080
        • Recruiting
        • Guangdong General Hospital
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

45 years to 79 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: 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.
Drug: Allisartan Isoproxil
Allisartan Isoproxil 240mg daily will be used to lower BP to below 120 mm Hg systolic.
Other Names:
  • Xinlitan
Drug: Amlodipine 5mg
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).
Other Names:
  • Qiaohean
Placebo Comparator: 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.
Other: Standard treatment by current guideline
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Composite of Major Adverse Cardiovascular and Cerebrovascular Events
Time Frame: 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
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Stroke
Time Frame: From date of randomization until the date of first documented incidence of stroke, assessed up to 60 months.
Stroke (ICD-Code I60, I61, I63, I64) is a focal neurological deficit with symptoms continuing for more than 24 hours or leading to death with no apparent cause other than vascular. Stroke as an endpoint in IPAD includes definite ischemic stroke, primary intracerebral hemorrhage and subarachnoid hemorrhage with evidence from CT or MRI scan within 14 days of onset or autopsy confirmation, and stroke of unknown type etiology when CT, MRI, or autopsy are not done and information is inadequate to diagnose the etiology definitely.
From date of randomization until the date of first documented incidence of stroke, assessed up to 60 months.
Cardiovascular Death
Time Frame: From date of randomization until the date of cardiovascular death, assessed up to 60 months.
Cardiovascular death include death caused by stroke, MI, HF, sudden death or any other death attributed to cardiovascular diseases. Sudden death (ICD-Code I46.1, R96) encompasses any death of unknown origin occurring instantly or within an estimated 24 hours after the onset of acute symptoms as well as unattended death for which no likely cause can be established by autopsy or recent medical history.
From date of randomization until the date of cardiovascular death, assessed up to 60 months.
Acute Myocardial Infarction
Time Frame: From date of randomization until the date of first documented incidence of acute MI, assessed up to 60 months.
Acute myocardial infarction (MI) (ICD-Code I21) is defined when any one of the following criteria occurs. (1) Detection of a rise and/or fall of cardiac biomarker values, with at least one value above the 99th percentile upper reference limit and with at least one of the following manifestations: symptoms of ischaemia that should have lasted for at least 30 minutes and should not have been responsive to sublingual administration of nitrates; new or presumed new significant ST-segment-T wave changes or new left bundle branch block (LBBB); development of pathological Q waves in the ECG; imaging evidence of new loss of viable myocardium or new regional wall motion abnormality. (2) Identification of an intracoronary thrombus by angiography or autopsy. (3) Cardiac death with symptoms suggestive of myocardial ischaemia and presumed new ischaemic ECG changes or new LBBB, but death occurred before cardiac biomarkers were obtained, or before cardiac biomarker values would be increased.
From date of randomization until the date of first documented incidence of acute MI, assessed up to 60 months.
Hospitalization of Unstable Angina
Time Frame: From date of randomization until the date of first documented hospitalization of unstable angina, assessed up to 60 months.
Unstable angina (ICD-Code I20.0) is defined as new onset or worsening angina pectoris requiring hospitalization with angiographically documented coronary atherosclerosis or transient electrocardiographic changes of the ST-segment or T-wave without evidence for myocardial necrosis. This diagnosis excludes patients with angina pectoris admitted to the hospital only for investigation.
From date of randomization until the date of first documented hospitalization of unstable angina, assessed up to 60 months.
Hospitalization of Congestive Heart Failure
Time Frame: From date of randomization until the date of first documented hospitalization of HF, assessed up to 60 months.
Congestive heart failure (HF) (ICD-Code I50) requires the presence of three conditions, namely symptoms, such as dyspnea, clinical signs, such as ankle edema or crepitations, and the necessity to initiate treatment with open-label diuretics, vasodilators or antihypertensive drugs. HF cases may also be adjudicated as chronic stable HF but this is not considered an outcome of the present study.
From date of randomization until the date of first documented hospitalization of HF, assessed up to 60 months.
All-cause Mortality
Time Frame: From date of randomization until the date of death from any causes, assessed up to 60 months.
All-cause mortality refers to death from any causes.
From date of randomization until the date of death from any causes, assessed up to 60 months.
Overt Albuminuria
Time Frame: From date of randomization until the date of confirmed development of overt albuminuria, assessed up to 60 months.
Overt albuminuria is defined as a ratio of urinary albumin (in mg/L) to urinary creatinine (in g/L) in urine specimens of at least 300 mg/g.
From date of randomization until the date of confirmed development of overt albuminuria, assessed up to 60 months.
Worsened Renal Function
Time Frame: From date of randomization until the date of first documented incidence of this event, assessed up to 60 months.
Estimated glomerular filtration rate (eGFR) decreased by more than 30% as compared with baseline
From date of randomization until the date of first documented incidence of this event, assessed up to 60 months.
End-Stage Renal Disease
Time Frame: From date of randomization until the date of documented diagnosis of end-stage renal disease, assessed up to 60 months.
End-stage renal disease (ICD-Code N18.5) is the need for long-term renal replacement therapy (dialysis).
From date of randomization until the date of documented diagnosis of end-stage renal disease, assessed up to 60 months.
Diabetic Retinopathy Requiring Interventional Operation or Surgery
Time Frame: From date of randomization until the date of first documented interventional or surgical operation for diabetic retinopathy, assessed up to 60 months.
Diabetic retinopathy requiring interventional operation or surgery is defined as the confirmed diagnosis of diabetic retinopathy, indicated for interventional operation or surgery, which is documented by ophthalmologists.
From date of randomization until the date of first documented interventional or surgical operation for diabetic retinopathy, assessed up to 60 months.
Peripheral Arterial Diseases Requiring Revascularization
Time Frame: From date of randomization until the date of first documented revascularization for peripheral arterial diseases, assessed up to 60 months.
Peripheral arterial diseases requiring revascularization are defined as the confirmed diagnosis of any one of the peripheral arterial diseases indicated for revascularization.
From date of randomization until the date of first documented revascularization for peripheral arterial diseases, assessed up to 60 months.
New Atrial Fibrillation or Flutter
Time Frame: From date of randomization until the date of first documented incidence of atrial fibrillation or flutter, assessed up to 60 months.
Atrial fibrillation or flutter is confirmed and documented with electrocardiogram indicating the occurence of atrial fibrillation or flutter. New development of atrial fibrillation or flutter is defined only if a participant at baseline has no history of and his or her electrocardiogram shows no signs of atrial fibrillation or flutter.
From date of randomization until the date of first documented incidence of atrial fibrillation or flutter, assessed up to 60 months.
Decline of Health-related Quality of Life
Time Frame: up to 60 months
Decline of Health-related Quality of Life, which is assessed using the EQ-5D-5L QOL questionnaire.
up to 60 months
Cancer
Time Frame: From date of randomization until the date of first confirmed diagnosis of a cancer of any type, assessed up to 60 months.
Cancer defined in the present study is recorded only when there is pathologically confirmed evidence.
From date of randomization until the date of first confirmed diagnosis of a cancer of any type, assessed up to 60 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
XueQing Yu

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Jiyan Chen, MD, Guangdong Provincial People's Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2018

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 21, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 24, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 29, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 10, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • GDREC2017192H

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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