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

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

Study Overview

• Status: Completed
• Conditions: T2DM (Type 2 Diabetes Mellitus); Nocturnal Hypertension
• Intervention / Treatment: Drug: Empagliflozin; Drug: Placebo

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 174
• Phase: Phase 4

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan
    • Fukuoka University Chikushi Hospital
  • Fukuoka, Japan
    • Kotake Hospital
  • Fukuoka, Japan
    • Onga Hospital
  • Gifu, Japan
    • Ishiguro Clinic
  • Gunma, Japan
    • Higashiagatsuma-machi National Health Insurance Clinic
  • Hyogo, Japan
    • Katsuya Iin
  • Miyagi, Japan
    • Minamisanriku Hospital
  • Saitama, Japan
    • Shibuya Clinic
  • Tochigi, Japan
    • Jichi Medical University Hospital
  • Tochigi, Japan
    • International University of Health and welfare Hospital
  • Tochigi, Japan
    • Utsunomiya higashi hospital
  • Tokyo, Japan
    • Kato Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Empagliflozin; 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; Empagliflozin 10mg/day once daily before or after breakfast; Other Names: Jardiance
Placebo Comparator: Placebo; 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; Placebo once daily before or after breakfast

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Jichi Medical University
• Collaborators: Eli Lilly and Company; Boehringer Ingelheim
• Investigators: Principal Investigator: Kazuomi Kario, MD, Jichi Medical University

Publications and helpful links

General Publications

• 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. 24-Hour Blood Pressure-Lowering Effect of an SGLT-2 Inhibitor in Patients with Diabetes and Uncontrolled Nocturnal Hypertension: Results from the Randomized, Placebo-Controlled SACRA Study. Circulation. 2018 Nov 29;139(18):2089-97. doi: 10.1161/CIRCULATIONAHA.118.037076. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2017
• Primary Completion (Actual): October 1, 2017
• Study Completion (Actual): March 1, 2018

Study Registration Dates

• First Submitted: December 26, 2016
• First Submitted That Met QC Criteria: February 8, 2017
• First Posted (Actual): February 10, 2017

Study Record Updates

• Last Update Posted (Actual): March 27, 2018
• Last Update Submitted That Met QC Criteria: March 25, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Hypertension; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Empagliflozin
• Other Study ID Numbers: 1245-131