SGLT-2i and ARB Combination Therapy in Patients With T2DM and Nocturnal Hypertension (SACRA Study)

Study Overview
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Brief Summary
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To explore the beneficial effects of 'empagliflozin + ARB' in comparison with 'placebo + ARB' on the reduction of nocturnal blood pressure in T2DM with hypertension

Detailed Description
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The study consists of a 8-week run-in period and a 12-week treatment period.

Conditions
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Nocturnal Hypertension, T2DM (Type 2 Diabetes Mellitus)

Intervention / Treatment
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* Drug: Empagliflozin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who meet the following criteria at the start of treatment are eligible for the study: Receiving stable treatment with anti-hypertensive including ARB for at least 8 weeks at baseline (0W). Receiving stable anti-diabetic treatment with/without anti-diabetics for at least 8 weeks at baseline (0W). HbA1c>=6.0%, <10% Seated office SBP 130-159mmHg or DBP 80-99mmHg Nocturnal hypertension (SBP>=115 mmHg) as measured by Home BP during 5days before baseline (0W). Age>=20 Exclusion Criteria: Patients who meet any of the following criteria are not eligible for the study: History of hypersensitivity to empagliflozin Breast-feeding, pregnant, possibly pregnant, or plan to become pregnant Treated with insulin or SU With renal dysfunction (eGFR<45mL/min/1.73m2) With liver dysfunction (AST or ALT is 3 times higher than reference value) Hypotension (systolic blood pressure < 90 mmHg) With pituitary gland dysfunction or adrenal gland dysfunction Heart failure patients whose NYHA class is IV Deemed ineligible for the study due to another reason by investigator History of diabetic ketoacidosis or diabetic come within 3 months before enrollment History of Acute myocardial infarction, unstable angina, cerebrovascular disease, or transient ischemic attack within 3 months before enrollment Patients who have undergone percutaneous transluminal coronary angioplasty (PCI) or coronary artery bypass graftin (CABG) within 3 months before enrollment Patients received SGLT2 inhibitor within 8 weeks before enrollment

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Empagliflozin<br>Empagliflozin 10mg/day is administrated orally before or after breakfast for 12 weeks while continuing the existing treatment for hypertension (include AngiotensinII Receptor Blocker [ARB]) and diabetes. | Drug: Empagliflozin<br>* Empagliflozin 10mg/day once daily before or after breakfast<br>* Other names: Jardiance;|
| Placebo Comparator: Placebo<br>Placebo is administrated orally before or after breakfast for 12 weeks while continuing the existing treatment for hypertension (include AngiotensinII Receptor Blocker [ARB]) and diabetes. | Drug: Placebo<br>* Placebo once daily before or after breakfast<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of nocturnal blood pressure measured by ABPM |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of Blood pressure measured by ABPM -24h Blood Pressure |  | 12 weeks | 
| Reduction of Blood pressure measured by ABPM -Daytime Blood Pressure |  | 12 weeks | 
| Reduction of Blood pressure measured by ABPM -Minimum nocturnal Blood Pressure |  | 12 weeks | 
| Reduction of Blood pressure measured by ABPM -Nocturnal blood pressure variability |  | 12 weeks | 
| Reduction of Metabolism-related factors -HbA1c |  | 12 weeks | 
| Reduction of Metabolism-related factors -body weight |  | 12 weeks | 
| Reduction of Metabolism-related factors -BMI |  | 12 weeks | 
| Reduction of Metabolism-related factors -lipids |  | 12 weeks | 
| Reduction of Metabolism-related factors -uric acid |  | 12 weeks | 
| Reduction of Metabolism-related factors -HOMA-R |  | 12 weeks | 
| Reduction of Metabolism-related factors -HOMA-beta |  | 12 weeks | 
| Change in Sleep efficacy -Sleep scale (Athens insomnia scale) |  | 12 weeks | 
| Change in Sleep efficacy -Frequency of nocturnal awakening |  | 12 weeks | 
| Change in Sleep efficacy -Frequency of nocturia |  | 12 weeks | 
| Changes in the measures of circulating volume -Plasma NT-proBNP |  | 12 weeks | 
| Changes in the measures of circulating volume -ANP |  | 12 weeks | 
| Changes in the measures of organ damage -Urinary albumin/creatinine excretion ratio |  | 12 weeks | 
| Changes in the measures of organ damage -Urinary Na/K |  | 12 weeks | 
| Changes in the measures of organ damage -eGFR |  | 12 weeks | 
| Changes in the measures of organ damage -cystatinC |  | 12 weeks | 
| The correlation between blood pressure and blood glucose control |  | 12 weeks | 
| The correlation between blood pressure and body weight |  | 12 weeks |