Clinical trial NCT02919059: Study to Asses the Effect of Dapagliflozin on Central Blood Pressure Reduction.
Official title: A Randomized, Unicenter, Parallel Study of the Effect of Dapagliflozin on Central Blood Pressure Reduction Compared to Glimepiride in Adult Subjects With Type 2 Diabetes Mellitus and Inadequate Glycemic Control.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Diabetes Mellitus, Type 2
Keywords: Diabetes Mellitus, Type 2
DM
Lead sponsor: IInstituto Gallego de Medicina Vascular
Sponsor class: OTHER
First posted: 2016-09-29
Enrollment: 159
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This superiority of central pressure versus peripheral measures to predict cardiovascular events has also been reported in general population or in elder people

Detailed description: The prognostic value of central systolic/diastolic pressure, central pulse pressure and AI has been well demonstrated, firstly after CAFÉ study, with 2073 hypertensive subjects followed up 3.4 years. It also evidenced higher prognostic value of central blood pressure compared to peripheral blood pressure. One year later, the STRONG study, showed central pulse pressure to be an independent cardiovascular risk factor as well as higher prognostic value compared to peripheral pulse pressure (Hazard ratio; 1,1510 mmHg Vs 1,10mmHg; X2: 13,4; p \< 0,001). Those subjects with higher central blood pressure and central pulse pressure showed higher incidence of cardiovascular events. This superiority of central pressure versus peripheral measures to predict cardiovascular events has also been reported in general population or in elder people.

Finally, it has been also reported that dapagliflozin modestly reduces systolic blood pressure in patients with T2DM who were mostly receiving treatment for hypertension. Despite office blood pressure remains the gold standard method for screening, diagnostic and treatment of hypertension, it has been also well demonstrated that ambulatory blood pressure monitoring (ABPM) better estimates cardiovascular risk and target organ damage than office blood pressure. It still remains unclear the effects on 24 hours blood pressure reduction with SGLT-2 inhibitors.

The effects of SGLT2 inhibitors on central blood pressure reduction have not been documented.

Eligibility criteria: Inclusion Criteria:

* T2DM subjects with uncontrolled glycaemia, based on HbA1c levels (10% ≥ HbA1c ≥ 7%) at Visit 1.
* Patients may be treated for \>3 months with a stable doses of metformin at optimal doses tolerated.
* Participants will be able to give and sign informed consent form.
* Age \> 18 years of either gender.

Exclusion Criteria:

* Patients with two or more different oral antihyperglycemic agents.
* HbA 1c levels \> 10%.
* Systolic BP \>160 mm Hg and/or diastolic BP \> 100 mm Hg before randomization.
* History of diabetic ketoacidosis, T1DM, pancreas or beta-cell transplantation or diabetes secondary to any condition.
* History of one or more severe hypoglycaemic episode within 6 months before screening.
* Myocardial infarction, unstable angina pectoris, congestive heart failure, life threatening arrhythmia, history of cerebrovascular accident within 3 months.
* Clinically relevant renal disease; defines if serum creatinine equal or lager than 1.5 mg/dl or eGFR \< 60 ml/min/1.73m2, at screening.
* Liver function abnormal: glutamic-oxalacetic transaminase lager than 2 times of upper limit normal or glutamic-pyruvic transaminase lager than 2 times of upper limit normal
* Existence of any serious systemic disease
* Allergic history to the compounds of study medication
* Can not comply the study protocol or misunderstand the informed consent form
* Women of childbearing potential will be required to use a double-barrier method of birth control throughout study participation. Women who are surgically sterile or documented post-menopausal for at least 2 years are not considered to be of childbearing potential.
* Pregnant or breast-feeding or planning to become pregnant during the study.
* History of alcohol abuse (\>350 g/week) within 3 years before screening.
* Concurrent therapy with medications that could be affect glycaemia (e.g. corticosteroids) or disallowed therapy (e.g. digoxin).
* Investigational drug treatment within the past 4 months
* Concomitant psychiatric diseases and/or habit/abuse of psychoactive substances
* Predictable lack of co-operation
* Shifts workers
* Employees of the investigator or study centre.

Primary outcomes:
measure: Effect of dapagliflozin relative to glimepiride at 24 weeks of treatment period regarding central systolic blood pressure
timeFrame: 24 weeks
Secondary outcomes:
measure: Effect of dapagliflozin relative to glimepiride at 24 weeks regarding central systolic/diastolic blood pressure
timeFrame: 24 weeks
measure: Effect of dapagliflozin relative to glimepiride at 24 weeks regarding central pulse pressure
timeFrame: 24 weeks
measure: Effect of dapagliflozin relative to glimepiride at 24 weeks of treatment with inadequate glycemic control regarding 24 hours ambulatory systolic/diastolic blood pressure
timeFrame: 24 weeks
measure: Type and number of Adverse events in patienteSafety and tolerability of dapagliflozin relative to glimepiride.
timeFrame: 28 weeks
measure: Effect of dapagliflozin relative to glimepiride at 24 weeks with inadequate glycemic control regarding augmentation pressure
timeFrame: 24 weeks
measure: Effect of dapagliflozin relative to glimepiride at 24 weeks with inadequate glycemic control regarding augmentation index
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Santiago de Compostela
country: Spain
facility: Hospital Nuestra Señora de la Esperanza
state: Galicia
Study officials:
affiliation: Hospital Nuestra Señora de la Esperanza
name: Alvaro Hermida, MD, PhD
role: STUDY_DIRECTOR
References: