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

Sponsor

Aristotle University Of Thessaloniki (Other)

Overall Status

Unknown status

CT.gov ID

NCT01001962

Collaborator

(none)

1,054

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Objectives:

Primary

Primary prevention of new onset of hypertension

Secondary

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

Condition or Disease	Intervention/Treatment	Phase
Hypertension Type II Diabetes	Drug: empagliflozin Drug: Metformin	Phase 4

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

Age between 45 and 60 years.
All patients are going to give their informed consent to participate in the study.
Patients who are not receiving antihypertensive or diabetes treatment (newly diagnosed diabetics)
BP between 130 to 140 mmHg for systolic BP (prehypertensives)
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 Design

Study Type:

Interventional

Anticipated Enrollment :

1054 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

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

Study Start Date :

Jan 1, 2016

Anticipated Primary Completion Date :

Jan 1, 2019

Anticipated Study Completion Date :

Jan 1, 2020

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

New onset of hypertension [36 months]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

45 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion criteria

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

Exclusion criteria