Canagliflozin in Patients With Acute Decompansted Heart Failure

Diabetes Mellitus Clinical Trial

— The CANA -AHF  

Official title:

Efficacy and Safety of Early Initiation of Canagliflozin in Patients With Acute Decompansted Heart Failure

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05364190
• Other study ID #: CL (2973)
• Status: Completed
• Phase: Phase 3
• Start date: June 4, 2022
• Est. completion date: December 1, 2023

Study information

• Verified date: June 2024
• Source: October 6 University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 142
• Est. completion date: December 1, 2023
• Est. primary completion date: September 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Heart Failure
• Chronic Heart Failure
• Diabetes Mellitus
• Heart Failure

Intervention

Drug:
• Canagliflozin
Canagliflozin will be used in hospitalized heart failure patients regardless of their diabetic state.
• Empagliflozin
Empagliflozin will be used in hospitalized heart failure patients regardless of their diabetic state.

Locations

Country	Name	City	State
Egypt	National heart institute	Giza

Sponsors (3)

Lead Sponsor	Collaborator
October 6 University	Cairo University, National Heart Institute, Egypt

Country where clinical trial is conducted

Egypt, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The cumulative mean of daily diuresis	which is define as total urine output in 24 hours during the hospitalization period.	After (day1)24 hours from hospital admission and until Day 5 or discharge if earlier
Secondary	Measuring diuretic response	which is the cumulative change in weight (kg) from enrollment until discharge adjusted for cumulative diuretic dose in IV furosemide or equivalents	Baseline to hospital discharge, an average of 5-6 days
Secondary	The change in the level of NT-pro BNP	The change in the level of NT-pro BNP between the hospital admission day and the day of discharge.	Baseline to hospital discharge, an average of 5-6 days
Secondary	Presence of symptoms of congestion and dyspnea at discharge	measured via the change in visual analogue scale (VAS) dyspnea score between enrollment day and the discharge day. the score goes between 0-10 where 0 = no breathlessness to 10 = worst breathlessness possible.	Baseline to hospital discharge, an average of 5-6 days.
Secondary	Intensive care unit (ICU) length of stay	measured as days from admission to ICU to discharge.	Baseline to hospital discharge, an average of 5-6 days
Secondary	The incidence of worsening of heart failure case	which is defined as failure of IV diuretic regimen to stabilize the patient state during hospitalization which requires the use of IV inotropic therapy	Baseline to hospital discharge, an average of 5-6 days.
Secondary	Fractional Excretion of Sodium (FENa)-based diuretic efficiency	FENa per 40 mg of IV furosemide equivalents of loop dose using spot urine collected 24 hours after continues infusion of loop dose beginning and every day until patients discharge from hospital.	Baseline to hospital discharge, an average of 5-6 days.
Secondary	Serum potassium	Serum potassium covariate with attention to both elevation and depression on a daily basis during hospitalization period.	Baseline to hospital discharge, an average of 5-6 days.
Secondary	Incidence of ketoacidosis	reporting ketoacidosis	Baseline to 90 days post discharge
Secondary	Serum glucose covariate adjusted for baseline with attention to both elevation	(> 400 mg/dL) and depression (< 70 mg/dL).	Baseline to hospital discharge, an average of 5-6 days.
Secondary	Incidence of symptomatic, sustained hypovolemic hypotension	systolic blood pressure < 90 mmHg over 30 minutes requiring fluid administration	Baseline to hospital discharge, an average of 5-6 days.
Secondary	In-hospital mortality	incidence of mortality	Baseline to hospital discharge, an average of 5-6 days.
Secondary	Hospital readmission within 90 days of discharge for heart failure	Re-hospitalization within 90 days from hospital discharge	within 90 post discharge
Secondary	Incidence of mortality within 90 days from discharge due cardiovascular cause	Incidence of mortality	within 90 post discharge
Secondary	The incidence of worsening of renal function	which is defined as a decline in the e-GFR of 50% or greater from the baseline during any follow-up points	Baseline to 90 post discharge
Secondary	Any reported adverse events during follow up period.	ketoacidosis, genital mycotic infection, urinary tract infection, Fournier's gangrene, fractures, or amputation	within 90 post discharge
Secondary	The progression of heart failure severity	via measuring Kansas City Cardiomyopathy Questionnaire - Total Symptom Score (KCCQ-TSS); .all KCCQ scores are scaled from 0 to 100 and frequently summarized in 25-point ranges, where scores represent health status as follows: 0 to 24: very poor to poor; 25 to 49: poor to fair; 50 to 74: fair to good; and 75 to 100: good to excellent	within 90 post discharge