Blood Pressure Control for Type 2 Diabetes

Study Overview
=================
Brief Summary
-----------------
The BP4DM study was initiated as a prospective randomized controlled trial to investigate the renal protection effect for tight blood pressure control for Taiwanese T2DM patients without previously diagnosed CV events. We set our primary outcome for the prevention of microalbuminuria development. The secondary outcomes include mortality, annual renal function declining rate, and development of cardiovascular events. The recruitment period for the RCT trial is from 2013 Oct to 2019 Dec. In addition, we also intend to continuously follow up all our recruited hypertensive diabetes patients for at least 10 years to observe their clinical outcomes including cardiovascular, renal, retinal outcomes and mortality.

Detailed Description
-----------------
The evidence from previous literature shows importance of the blood pressure control in T2DM. About 20% (16-29%) reduction in microalbuminuria development can be reached by continuously lowering blood pressure level from 154/87 mmHg to 144/82 mmHg (the UKPDS), to 134.7/74.8 mmHg (the ADVANCE study), and even to 119.3/64.4 mmHg (the ACCORD study). However, several limitations are also inherent in the above well-known studies. First, most of the recruited participants previous trials were Caucasians. Although 3293 Chinese patients were recruited in the ADVANCE study, they only accounted for 29.6% of total enrollees in that trial. The representative of Asian population is inadequate. There is also lack of domestic evidence-based guideline designated for Taiwanese T2DM patients in optimizing their blood pressure control. In addition, some characteristics in Asian T2DM population are different from what have been observed in the Caucasian T2DM patients. For example, there is BMI discrepancy between T2DM in Western and Eastern countries, more ACEi/ARB side effects (e.g., cough) observed in Asian population, and the possible difference in CKD/ESRD incidence in T2DM between different ethnic groups. Moreover, the enrollees in most well-known trials (e.g., ADVANCE and ACCORD studies) were those who suffered from at least one cardiovascular risk factor for secondary prevention. To our best knowledge, there is no study designed to evaluate effectiveness of blood pressure control for T2DM patients without previous CV events. Therefore, we initiated a prospective randomized controlled trial to investigate the renal protection effect for tight blood pressure control for Taiwanese T2DM patients without previously diagnosed CV events. We set our primary outcome for the prevention of microalbuminuria development to partly respond to the urgent need for this society in solving the huge burden caused by the high incidence and prevalence of diabetic nephropathy in Taiwan. The study includes two parts: (1) a RCT trial, (2) an observational cohort study. The recruitment period of this study is from 2013 Oct to 2019 Dec. The RCT trial will be ended in 2019 Dec. In addition, we also intend to continuously follow up all our recruited hypertensive diabetes patients for at least 10 years to observe their clinical outcomes including cardiovascular, renal, retinal outcomes and mortality (the part of the observational cohort study).

Official Title
-----------------
Blood Pressure Control to Reduce Renal Risk for Type 2 Diabetes Mellitus

Conditions
-----------------
Type 2 Diabetes Mellitus, Hypertension

Intervention / Treatment
-----------------
* Combination Product: drug adjustment and behavioral modification


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria (for both RCT trial and observational cohort study): type 2 DM with hypertension Exclusion Criteria (for both RCT trial and observational cohort study): ACR>300 mg/g prior history of severe CV events (e.g., MI, stroke, heart failure>NYHA functional class III) dialysis, blindness, amputation, liver cirrhosis, cancer under active treatment pregnant women proteinuria which is unrelated with diabetes urinary tract stone > 0.5 cm Stricter Exclusion Criteria (for RCT trial only): unstable BP (SBP>160 or DBP>100) unstable glycemic control (HbA1c>10%) K>5.0 meq/L

Ages Eligible for Study
-----------------
Minimum Age: 30 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: tight BP<br>Interventions: anti-hypertension drug prescription by physician and case management by health educator. Blood pressure is targeted at 120/80 mmHg in the tight BP control group. | Combination Product: drug adjustment and behavioral modification<br>* anti-hypertension drug prescription by physician and case management by health educator<br>|
| Placebo Comparator: usual BP<br>Interventions: The physicians follow their usual care patterns to prescribe anti-HT drugs. Blood pressure is targeted at < 140/90 mmHg in the usual BP control group. | Combination Product: drug adjustment and behavioral modification<br>* anti-hypertension drug prescription by physician and case management by health educator<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| development of microalbuminuria | indicator of microalbuminuria: urine ACR | up to 10 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mortality | all-cause mortality and CV-specific mortality | up to 10 years | 
| annual renal function declining rate | indicator of renal function: eGFR assessed by CKD-EPI formula | up to 10 years | 
| development of cardiovascular events | cardiovascular events include MI, heart failure, and stroke | up to 10 years |