Canagliflozin in Patients With Acute Decompansted Heart Failure (The CANA -AHF)

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

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus; Chronic Heart Failure; Acute Heart Failure
• Intervention / Treatment: Drug: Canagliflozin; Drug: Empagliflozin

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.

• Study Type: Interventional
• Enrollment (Actual): 142
• Phase: Phase 3

Contacts and Locations

Study Locations

• Egypt
  • Giza, Egypt
    • National Heart Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A(Intervention group); patients will receive 100 mg canagliflozin initiated within 24 hours from patients hospital admission due to signs of hypervolemic state. All patients also will be prescribed the conventional diuretic therapy and other medications such as angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), beta-blockers, angiotensin receptor-neprilysin inhibitor (ARNI) and mineralocorticoid receptor antagonists (MRAs). Canagliflozin will be continued for 90 days after hospital discharge	Drug: Canagliflozin; Canagliflozin will be used in hospitalized heart failure patients regardless of their diabetic state.
Active Comparator: Group B; patients will receive 10 mg Empagliflozin initiated within 24 hours from patients hospital admission due to signs of a hypervolemic state.All patients also will be prescribed conventional diuretic therapy and other medications including ACEIs, ARBs, beta-blockers, ARNI, and MRAs.Empagliflozin will be continued for 90 days after hospital discharge	Drug: Empagliflozin; Empagliflozin will be used in hospitalized heart failure patients regardless of their diabetic state.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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.
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
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.
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.
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.
Incidence of ketoacidosis	reporting ketoacidosis	Baseline to 90 days post discharge
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.
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.
In-hospital mortality	incidence of mortality	Baseline to hospital discharge, an average of 5-6 days.
Hospital readmission within 90 days of discharge for heart failure	Re-hospitalization within 90 days from hospital discharge	within 90 post discharge
Incidence of mortality within 90 days from discharge due cardiovascular cause	Incidence of mortality	within 90 post discharge
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
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
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

Collaborators and Investigators

• Sponsor: October 6 University
• Collaborators: Cairo University; National Heart Institute, Egypt

Study record dates

Study Major Dates

• Study Start (Actual): June 4, 2022
• Primary Completion (Actual): December 1, 2023
• Study Completion (Actual): March 1, 2024

Study Registration Dates

• First Submitted: April 25, 2022
• First Submitted That Met QC Criteria: May 3, 2022
• First Posted (Actual): May 6, 2022

Study Record Updates

• Last Update Posted (Actual): July 11, 2024
• Last Update Submitted That Met QC Criteria: July 10, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Canagliflozin; NT-proBNP; Hospitalized heart failure patients; I.V loop diuretic
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Empagliflozin; Canagliflozin
• Other Study ID Numbers: CL (2973)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The study results will be duplicated after the end of the study
• IPD Sharing Time Frame: 2024
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No