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

Browse trials for

• Diabetes Mellitus, Type 2 9,339
• Prehypertension 145

Study arms

• 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 · Drug: Amlodipine 5mg

• 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

Interventions

• DrugAllisartan Isoproxil

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

  Also known as: Xinlitan

• DrugAmlodipine 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).

  Also known as: Qiaohean

• OtherStandard 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.

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.

   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

Secondary outcomes

1. Stroke

   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.

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

2. Cardiovascular Death

   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.

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

3. Acute Myocardial Infarction

   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.

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

4. Hospitalization of Unstable Angina

   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.

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

5. Hospitalization of Congestive Heart Failure

   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.

   Time frame: From date of randomization until the date of first documented hospitalization of HF, assessed up to 60 months.

6. All-cause Mortality

   All-cause mortality refers to death from any causes.

   Time frame: From date of randomization until the date of death from any causes, assessed up to 60 months.

7. Overt Albuminuria

   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.

   Time frame: From date of randomization until the date of confirmed development of overt albuminuria, assessed up to 60 months.

8. Worsened Renal Function

   Estimated glomerular filtration rate (eGFR) decreased by more than 30% as compared with baseline

   Time frame: From date of randomization until the date of first documented incidence of this event, assessed up to 60 months.

9. End-Stage Renal Disease

   End-stage renal disease (ICD-Code N18.5) is the need for long-term renal replacement therapy (dialysis).

   Time frame: From date of randomization until the date of documented diagnosis of end-stage renal disease, assessed up to 60 months.

10. Diabetic Retinopathy Requiring Interventional Operation or Surgery

    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.

    Time frame: From date of randomization until the date of first documented interventional or surgical operation for diabetic retinopathy, assessed up to 60 months.

11. Peripheral Arterial Diseases Requiring Revascularization

    Peripheral arterial diseases requiring revascularization are defined as the confirmed diagnosis of any one of the peripheral arterial diseases indicated for revascularization.

    Time frame: From date of randomization until the date of first documented revascularization for peripheral arterial diseases, assessed up to 60 months.

12. New Atrial Fibrillation or Flutter

    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.

    Time frame: From date of randomization until the date of first documented incidence of atrial fibrillation or flutter, assessed up to 60 months.

13. Decline of Health-related Quality of Life

    Decline of Health-related Quality of Life, which is assessed using the EQ-5D-5L QOL questionnaire.

    Time frame: up to 60 months

14. Cancer

    Cancer defined in the present study is recorded only when there is pathologically confirmed evidence.

    Time frame: From date of randomization until the date of first confirmed diagnosis of a cancer of any type, assessed up to 60 months.