Effect of dapagliflozin on flow-mediated dilation and blood pressure (DAPA-BP): a phase III, randomized, open-label, parallel group study in hypertensive patients with controlled type 2 diabetes

INTERVENTION: Trade Name: FORXIGA ‐ 10 MG ‐ COMPRESSE RIVESTITE CON FILM‐ USO ORALE ‐ BLISTER CALENDARIZZATO (ALU/ALU) ‐ 28 COMPRESSE Product Name: FORXIGA Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: DAPAGLIFLOZIN CAS Number: 461432‐26‐8 Current Sponsor code: NON DISPONIBILE Other descriptive name: DAPAGLIFLOZIN Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 10‐ Trade Name: ESIDREX ‐ 25 MG COMPRESSE 20 COMPRESSE Product Name: ESIDREX Product Code: NON DISPONIBILE Pharmaceutical Form: Tablet INN or Proposed INN: IDROCLOROTIAZIDE CAS Number: 58‐93‐5 Current Sponsor code: NON DISPONIBILE Other descriptive name: IDROCLOROTIAZIDE Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 25‐ CONDITION: Arterial hypertension ; MedDRA version: 20.0 Level: LLT Classification code 10020775 Term: Hypertension arterial System Organ Class: 100000004866 Therapeutic area: Diseases [C] ‐ Cardiovascular Diseases [C14] PRIMARY OUTCOME: ; Secondary Objective: a) To assess the effects of short‐term (4 weeks) treatment period with the two treatments on the following parameters:; • Renal Resistive Index (RRI) before and after nitrate administration; • Endothelial function as flow mediated dilation (FMD) of brachial artery; • Carotid to femoral pulse wave velocity; • Peripheral and Central BP measurement; • 24h BP monitoring; • 24h urinary albumin excretion; • 24h diuresis for glucose, Na, K, Cl, Ca, Mg urinary excretion determination; • Free water clearance and Na fractional excretion; • PRA, aldosterone, catecholamines plasma levels; • Daily glucose profile (7 determination in a day); Safety objective; • Adverse events and adverse drug reactions; • Estimated glomerular filtration rate (eGFR) (based on CKD‐EPI formula starting from serum creatinine); • Routine laboratory parameters (haematology, blood chemistry and urinalysis).; Main Objective: Aim of this project will be to evaluate the effect short‐term (4 weeks) administration of dapagliflozin as compared to a thiazide diuretic on endothelial function as flow mediated dilation (FMD) of the brachial artery. Primary end point(s): Change in endothelial function of the brachial artery, measured as flow mediated dilation (FMD), after 4‐week administration of dapagliflozin or hydrochlorothiazide (short‐term study). Timepoint(s) of evaluation of this end point: 4 WEEKS SECONDARY OUTCOME: Secondary end point(s): Safety endpoints (adverse events and adverse drug reactions: eGFR haematology and blood chemistry laboratory parameters and urinalysis). Timepoint(s) of evaluation of this end point: 4 WEEKS INCLUSION CRITERIA: Inclusion criteria for the main study (short‐term study): 1. Provision of informed consent prior to any study specific procedures 2. Men or post‐menopausal women that express their willing to participate in the study by signing the informed consent 3. Subjects aged 30‐69 years (inclusive) 4. T2DM patients with adequate glucose control (HbA1c<7.5%), achieved with any oral anti‐hyperglycemic treatment, whose BP values are not at target (e.g. clinic BP >140/90 mmHg or home BP >135/85 mmHg despite a therapeutic dose of ACE‐inhibitors Inclusion criteria for the substudy (acute study): 1. Provision of informed consent prior to any study specific procedures 2. Men or post‐menopausal women that express their willing to participate in the study by signing the informed consent 3. Subjects aged 30‐69 years