Double Blind Placebo Study of JARDIANCE® (Empagliflozin) in Prehypertensives Type II Diabetics (PREHYPD)

Double Blind Comparison Study of JARDIANCE® (Empagliflozin) in Prehypertensives Type II Diabetics With Metformin

Objectives:

Primary

1. Primary prevention of new onset of hypertension

Secondary

1. Reduction of 24h BP in type II diabetics with prehypertension
2. Reduction of non dipping status, day and nighttime BP, morning BP surge in subjects receiving EMPAGLIFLOZIN
3. Reduction in the total cardiovascular risk
4. 3 years morbidity and mortality rates
5. Arterial de-stiffening, reduction in central aortic blood pressure in subjects receiving EMPAGLIFLOZIN

Study Overview

• Status: Unknown
• Conditions: Hypertension; Type II Diabetes
• Intervention / Treatment: Drug: Metformin; Drug: empagliflozin

Detailed Description

Study rationale: The majority of patients with diabetes are having higher blood pressure than optimal. More than 30% of patients with type II diabetes are prehypertensives with systolic blood pressure between 130 and 140 mmHg. If a drug for diabetes has an impact on blood pressure in such patients then this drug will reduce cardiovascular risk beyond the reduction on glucose levels. There are some evidence that EMPAGLIFLOZIN is reducing blood pressure levels but a comprehensive study is not available.

Timelines and Study duration:

Start date : 01-01-2016 End date : 01-01-2019 Clinical Study Report date: June 2018 Publication date: 2018, 2018, 2019,2020

Methodology:

Inclusion criteria

1. Age between 45 and 60 years.
2. All patients are going to give their informed consent to participate in the study.
3. Patients who are not receiving antihypertensive or diabetes treatment (newly diagnosed diabetics)
4. BP between 130 to 140 mmHg for systolic BP (prehypertensives)
5. Type II diabetes (HbA1c 7.0-8.0)

Exclusion criteria Known oversensitiveness, chronic renal disease (GFR<60 ml/min) or ESRD, heart or respiratory failure, recent MI, shock and pregnancy or lactation.

Study drugs:

Clinical examination 0,1,6,12,24,36 months.

• Duration and follow-up: 3 years
• Collected data: Ambulatory blood pressure monitoring, 24h SBP and DBP in time 0,12, 24 months.
• BMI, waist/hip ratio in time 0, 12, 24,36 months.
• HbA1c, insulin in time 0, 1, 6,12, 24,36 months.
• K, Na, Cr, BUN, Chol, Tg, HDL, LDL,ALT, AST in time 0, 1, 6,12, 24,36 months.

Number of patients: 1054

Sample size justification:

The reduction in mean 24h SBP expected to be 2.5 mmHg. Previous studies from our group reported an 12-14mmHg SD for 24h mean SBP. The sample size required at the two sided 5% significance level and 90% power is 527 patients per drug arm.

Statistics/Data Analysis Stata Estimated sample size for two-sample comparison of means Test Ho: m1 = m2, where m1 is the mean in population 1 and m2 is the mean in population 2

Assumptions:

alpha = 0.0500 (two-sided) power = 0.9000 m1 = 130 m2 = 132.5 sd1 = 12 sd2 = 13 n2/n1 = 1.00

Estimated required sample sizes:

n1 = 527 n2 = 527

Population: Diabetes, prehypertension, outpatients. I

• Study Type: Interventional
• Enrollment (Anticipated): 1054
• Phase: Phase 4

Contacts and Locations

Study Locations

• Greece
  • Thessaloniki, Greece
    • Hypertension 24h ABPM center Papageorgiou Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria

1. Age between 45 and 65 years.
2. All patients are going to give their informed consent to participate in the study.
3. Patients who are not receiving antihypertensive or diabetes treatment (newly diagnosed diabetics)
4. BP between 130 to 140 mmHg for systolic BP (prehypertensives)
5. Type II diabetes (HbA1c 7.0-8.0)

Exclusion criteria

1. Known oversensitiveness
2. chronic renal disease (GFR<60 ml/min) or ESRD
3. heart or respiratory failure, recent MI, shock
4. pregnancy or lactation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Metformin; 527 Patients treated with Metformin 850x2mg titrated to 1000x2mg Daily oral	Drug: Metformin; ACTIVE TREATMENT FOR DIABETES; Other Names: GLUCOPHAGE
ACTIVE_COMPARATOR: Empagliflozin; 527 Patients treated with empagliflozin 10mg titrated to 25 mg Daily oral	Drug: empagliflozin; ACTIVE TREATMENT FOR DIABETES; Other Names: JARDIANCE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
New onset of hypertension	36 months

Secondary Outcome Measures

Outcome Measure	Time Frame
24h blood pressure levels	36 months
Total cardiovascular risk	36 months
Morbidity cardiovascular	36 months
Arterial stiffness	36 months
Central aortic blood pressure	36 months
Mortality cardiovascular	36 months

Collaborators and Investigators

• Sponsor: Aristotle University Of Thessaloniki

Publications and helpful links

General Publications

• Gnesin F, Thuesen ACB, Kahler LKA, Madsbad S, Hemmingsen B. Metformin monotherapy for adults with type 2 diabetes mellitus. Cochrane Database Syst Rev. 2020 Jun 5;6(6):CD012906. doi: 10.1002/14651858.CD012906.pub2.

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (ANTICIPATED): January 1, 2019
• Study Completion (ANTICIPATED): January 1, 2020

Study Registration Dates

• First Submitted: October 26, 2009
• First Submitted That Met QC Criteria: October 26, 2009
• First Posted (ESTIMATE): October 27, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): April 7, 2015
• Last Update Submitted That Met QC Criteria: April 6, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: Hypertension in type II diabetes; Cardiovascular morbidity and mortality
• 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; Metformin; Empagliflozin
• Other Study ID Numbers: PREHYPERTENSION