Clinical trial NCT05364190: Canagliflozin in Patients With Acute Decompansted Heart Failure
Official title: Efficacy and Safety of Early Initiation of Canagliflozin in Patients With Acute Decompansted Heart Failure
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Heart Failure
Acute Heart Failure
Diabetes Mellitus
Keywords: Canagliflozin
Hospitalized heart failure patients
I.V loop diuretic
NT-proBNP
Lead sponsor: October 6 University
Sponsor class: OTHER
Collaborators: name: Cairo University
name: National Heart Institute, Egypt
First posted: 2022-05-06
Enrollment: 142
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study aims to investigate the efficacy and safety of the early initiation of canagliflozin treatment in hospitalized heart failure patients with volume overload (warm-wet) who require the use of I.V loop diuretic during the hospitalization period.

Detailed description: The study will focus on the role of adding canagliflozin to I.V loop diuretic therapy early in unstable hospitalized acute heart failure patients regardless of diabetic state, patients who will be included in the study will continue on canagliflozin for 3 months after hospital discharge to evaluate the incidence of re-hospitalization, mortality rate and other benefits related to HF symptoms will be investigated.

Eligibility criteria: Inclusion Criteria:

Randomized within 24 of presentation during hospital admission for hypervolemic ADHF with evidence of congestion defined by the presence of any of the following signs or symptoms:

Peripheral edema Ascites Jugular venous pressure \> 10 mmHg Orthopnea Paroxysmal nocturnal dyspnea 2.5 kg weight gain Signs of congestion on chest X-ray or lung ultrasound If pulmonary artery catheterization is available pulmonary capillary wedge pressure \> 19 mmHg plus a systemic physical examination finding of hypervolemia.

Planned use of intravenous (IV) loop diuretic therapy during the current hospitalization Estimated glomerular filtration rate (e-GFR) \> 30 mL/min/1.73 m2 based on the Modification of Diet in Renal Disease (MDRD) equation.

Exclusion Criteria:

Type 1 diabetes Serum glucose \< 80 mg/dL Systolic blood pressure \< 90 mmHg Requirement of IV inotropic therapy History of hypersensitivity to any SGLT-2 inhibitors Already receiving therapy with an SGLT2 inhibitor Women who are pregnant or breastfeeding Severe anemia (Hemoglobin \< 7.5 g/dL)(24) Severe uncorrected aortic or mitral stenosis Inability to perform standing weights or measure urine output accurately Signs of ketoacidosis and/or hyperosmolar hyperglycaemic syndrome (pH \>7.3 and glucose \> 250 mg/dL and HCO3 \> 18 mmol/L) in diabetic patients at the time of inclusion to the study.

The use of other diuretic therapies including; ≥100 mg/day spironolactone doses, ≥ 100 mg/day eplerenone, metolazone, hydrochlorothiazide, or other thiazides, systemic acetazolamide for the indication of diuretics, triamterene, or amiloride therapy.

The use of other medications possessing natriuretic effect as nesiritide, or arginine vasopressin antagonists.

Diffuse anasarca with 4+ edema and projected hypervolemia exceeding 18 kg. Severe hepatic impairment (Child-Pugh class C). Patients on hemodialysis Acute myocardial infarction with symptoms of acute ischemia or changes on electrocardiogram

Primary outcomes:
measure: The cumulative mean of daily diuresis
timeFrame: After (day1)24 hours from hospital admission and until Day 5 or discharge if earlier
Secondary outcomes:
measure: Measuring diuretic response
timeFrame: Baseline to hospital discharge, an average of 5-6 days
measure: The change in the level of NT-pro BNP
timeFrame: Baseline to hospital discharge, an average of 5-6 days
measure: Presence of symptoms of congestion and dyspnea at discharge
timeFrame: Baseline to hospital discharge, an average of 5-6 days.
measure: Intensive care unit (ICU) length of stay
timeFrame: Baseline to hospital discharge, an average of 5-6 days
measure: The incidence of worsening of heart failure case
timeFrame: Baseline to hospital discharge, an average of 5-6 days.
measure: Fractional Excretion of Sodium (FENa)-based diuretic efficiency
timeFrame: Baseline to hospital discharge, an average of 5-6 days.
measure: Serum potassium
timeFrame: Baseline to hospital discharge, an average of 5-6 days.
measure: Incidence of ketoacidosis
timeFrame: Baseline to 90 days post discharge
measure: Serum glucose covariate adjusted for baseline with attention to both elevation
timeFrame: Baseline to hospital discharge, an average of 5-6 days.
measure: Incidence of symptomatic, sustained hypovolemic hypotension
timeFrame: Baseline to hospital discharge, an average of 5-6 days.
measure: In-hospital mortality
timeFrame: Baseline to hospital discharge, an average of 5-6 days.
measure: Hospital readmission within 90 days of discharge for heart failure
timeFrame: within 90 post discharge
measure: Incidence of mortality within 90 days from discharge due cardiovascular cause
timeFrame: within 90 post discharge
measure: The incidence of worsening of renal function
timeFrame: Baseline to 90 post discharge
measure: Any reported adverse events during follow up period.
timeFrame: within 90 post discharge
measure: The progression of heart failure severity
timeFrame: within 90 post discharge
Other outcomes:
Locations:
city: Giza
country: Egypt
facility: National heart institute
Study officials:
References: