Clinical trial NCT03050229: SGLT-2i and ARB Combination Therapy in Patients With T2DM and Nocturnal Hypertension (SACRA Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Nocturnal Hypertension
T2DM (Type 2 Diabetes Mellitus)
Lead sponsor: Jichi Medical University
Sponsor class: OTHER
Collaborators: name: Boehringer Ingelheim
name: Eli Lilly and Company
First posted: 2017-02-10
Enrollment: 174
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: The study consists of a 8-week run-in period and a 12-week treatment period.

Eligibility criteria: 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

Primary outcomes:
measure: Reduction of nocturnal blood pressure measured by ABPM
timeFrame: 12 weeks
Secondary outcomes:
measure: Reduction of Blood pressure measured by ABPM -24h Blood Pressure
timeFrame: 12 weeks
measure: Reduction of Blood pressure measured by ABPM -Daytime Blood Pressure
timeFrame: 12 weeks
measure: Reduction of Blood pressure measured by ABPM -Minimum nocturnal Blood Pressure
timeFrame: 12 weeks
measure: Reduction of Blood pressure measured by ABPM -Nocturnal blood pressure variability
timeFrame: 12 weeks
measure: Reduction of Metabolism-related factors -HbA1c
timeFrame: 12 weeks
measure: Reduction of Metabolism-related factors -body weight
timeFrame: 12 weeks
measure: Reduction of Metabolism-related factors -BMI
timeFrame: 12 weeks
measure: Reduction of Metabolism-related factors -lipids
timeFrame: 12 weeks
measure: Reduction of Metabolism-related factors -uric acid
timeFrame: 12 weeks
measure: Reduction of Metabolism-related factors -HOMA-R
timeFrame: 12 weeks
measure: Reduction of Metabolism-related factors -HOMA-beta
timeFrame: 12 weeks
measure: Change in Sleep efficacy -Sleep scale (Athens insomnia scale)
timeFrame: 12 weeks
measure: Change in Sleep efficacy -Frequency of nocturnal awakening
timeFrame: 12 weeks
measure: Change in Sleep efficacy -Frequency of nocturia
timeFrame: 12 weeks
measure: Changes in the measures of circulating volume -Plasma NT-proBNP
timeFrame: 12 weeks
measure: Changes in the measures of circulating volume -ANP
timeFrame: 12 weeks
measure: Changes in the measures of organ damage -Urinary albumin/creatinine excretion ratio
timeFrame: 12 weeks
measure: Changes in the measures of organ damage -Urinary Na/K
timeFrame: 12 weeks
measure: Changes in the measures of organ damage -eGFR
timeFrame: 12 weeks
measure: Changes in the measures of organ damage -cystatinC
timeFrame: 12 weeks
measure: The correlation between blood pressure and blood glucose control
timeFrame: 12 weeks
measure: The correlation between blood pressure and body weight
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Fukuoka
country: Japan
facility: Fukuoka University Chikushi Hospital
city: Fukuoka
country: Japan
facility: Kotake Hospital
city: Fukuoka
country: Japan
facility: Onga Hospital
city: Gifu
country: Japan
facility: Ishiguro Clinic
city: Gunma
country: Japan
facility: Higashiagatsuma-machi National Health Insurance Clinic
city: Hyogo
country: Japan
facility: Katsuya Iin
city: Miyagi
country: Japan
facility: Minamisanriku Hospital
city: Saitama
country: Japan
facility: Shibuya Clinic
city: Tochigi
country: Japan
facility: International University of Health and Welfare Hospital
city: Tochigi
country: Japan
facility: Jichi Medical University hospital
city: Tochigi
country: Japan
facility: Utsunomiya higashi hospital
city: Tokyo
country: Japan
facility: Kato Clinic
Study officials:
affiliation: Jichi Medical University
name: Kazuomi Kario, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kario K, Okada K, Kato M, Nishizawa M, Yoshida T, Asano T, Uchiyama K, Niijima Y, Katsuya T, Urata H, Osuga JI, Fujiwara T, Yamazaki S, Tomitani N, Kanegae H. Twenty-Four-Hour Blood Pressure-Lowering Effect of a Sodium-Glucose Cotransporter 2 Inhibitor in Patients With Diabetes and Uncontrolled Nocturnal Hypertension: Results From the Randomized, Placebo-Controlled SACRA Study. Circulation. 2019 Apr 30;139(18):2089-2097. doi: 10.1161/CIRCULATIONAHA.118.037076. Epub 2018 Nov 29.