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

Primary Purpose

Chronic Heart Failure, Acute Heart Failure, Diabetes Mellitus

Status

Recruiting

Phase

Phase 3

Locations

Egypt

Study Type

Interventional

Intervention

Canagliflozin

Empagliflozin

About this trial

This is an interventional treatment trial for Chronic Heart Failure focused on measuring Canagliflozin, Hospitalized heart failure patients, I.V loop diuretic, NT-proBNP

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

National heart instituteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Group A(Intervention group)

Group B

Arm Description

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

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

Outcomes

Primary Outcome Measures

The cumulative mean of daily diuresis

which is define as total urine output in 24 hours during the hospitalization period.

Secondary Outcome Measures

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

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.

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.

Intensive care unit (ICU) length of stay

measured as days from admission to ICU to discharge.

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

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.

Serum potassium

Serum potassium covariate with attention to both elevation and depression on a daily basis during hospitalization period.

Incidence of ketoacidosis

reporting ketoacidosis

Serum glucose covariate adjusted for baseline with attention to both elevation

(> 400 mg/dL) and depression (< 70 mg/dL).

Incidence of symptomatic, sustained hypovolemic hypotension

systolic blood pressure < 90 mmHg over 30 minutes requiring fluid administration

In-hospital mortality

incidence of mortality

Hospital readmission within 90 days of discharge for heart failure

Re-hospitalization within 90 days from hospital discharge

Incidence of mortality within 90 days from discharge due cardiovascular cause

Incidence of mortality

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

Any reported adverse events during follow up period.

ketoacidosis, genital mycotic infection, urinary tract infection, Fournier's gangrene, fractures, or amputation

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

Full Information

NCT ID

NCT05364190

First Posted

April 25, 2022

Last Updated

September 12, 2023

Sponsor

October 6 University

Collaborators

Cairo University, National Heart Institute, Egypt

1. Study Identification

Unique Protocol Identification Number

NCT05364190

Brief Title

Canagliflozin in Patients With Acute Decompansted Heart Failure

Acronym

The CANA -AHF

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Recruiting

Study Start Date

June 4, 2022 (Actual)

Primary Completion Date

October 1, 2023 (Anticipated)

Study Completion Date

November 9, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

October 6 University

Collaborators

Cairo University, National Heart Institute, Egypt

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Heart Failure, Acute Heart Failure, Diabetes Mellitus

Keywords

Canagliflozin, Hospitalized heart failure patients, I.V loop diuretic, NT-proBNP

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

144 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Group A(Intervention group)

Arm Type

Experimental

Arm Description

Arm Title

Group B

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Canagliflozin

Intervention Description

Canagliflozin will be used in hospitalized heart failure patients regardless of their diabetic state.

Intervention Type

Drug

Intervention Name(s)

Empagliflozin

Intervention Description

Empagliflozin will be used in hospitalized heart failure patients regardless of their diabetic state.

Primary Outcome Measure Information:

Title

The cumulative mean of daily diuresis

Description

which is define as total urine output in 24 hours during the hospitalization period.

Time Frame

After (day1)24 hours from hospital admission and until Day 5 or discharge if earlier

Secondary Outcome Measure Information:

Title

Measuring diuretic response

Description

which is the cumulative change in weight (kg) from enrollment until discharge adjusted for cumulative diuretic dose in IV furosemide or equivalents

Time Frame

Baseline to hospital discharge, an average of 5-6 days

Title

The change in the level of NT-pro BNP

Description

The change in the level of NT-pro BNP between the hospital admission day and the day of discharge.

Time Frame

Baseline to hospital discharge, an average of 5-6 days

Title

Presence of symptoms of congestion and dyspnea at discharge

Description

Time Frame

Baseline to hospital discharge, an average of 5-6 days.

Title

Intensive care unit (ICU) length of stay

Description

measured as days from admission to ICU to discharge.

Time Frame

Baseline to hospital discharge, an average of 5-6 days

Title

The incidence of worsening of heart failure case

Description

which is defined as failure of IV diuretic regimen to stabilize the patient state during hospitalization which requires the use of IV inotropic therapy

Time Frame

Baseline to hospital discharge, an average of 5-6 days.

Title

Fractional Excretion of Sodium (FENa)-based diuretic efficiency

Description

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.

Time Frame

Baseline to hospital discharge, an average of 5-6 days.

Title

Serum potassium

Description

Serum potassium covariate with attention to both elevation and depression on a daily basis during hospitalization period.

Time Frame

Baseline to hospital discharge, an average of 5-6 days.

Title

Incidence of ketoacidosis

Description

reporting ketoacidosis

Time Frame

Baseline to 90 days post discharge

Title

Serum glucose covariate adjusted for baseline with attention to both elevation

Description

(> 400 mg/dL) and depression (< 70 mg/dL).

Time Frame

Baseline to hospital discharge, an average of 5-6 days.

Title

Incidence of symptomatic, sustained hypovolemic hypotension

Description

systolic blood pressure < 90 mmHg over 30 minutes requiring fluid administration

Time Frame

Baseline to hospital discharge, an average of 5-6 days.

Title

In-hospital mortality

Description

incidence of mortality

Time Frame

Baseline to hospital discharge, an average of 5-6 days.

Title

Hospital readmission within 90 days of discharge for heart failure

Description

Re-hospitalization within 90 days from hospital discharge

Time Frame

within 90 post discharge

Title

Incidence of mortality within 90 days from discharge due cardiovascular cause

Description

Incidence of mortality

Time Frame

within 90 post discharge

Title

The incidence of worsening of renal function

Description

which is defined as a decline in the e-GFR of 50% or greater from the baseline during any follow-up points

Time Frame

Baseline to 90 post discharge

Title

Any reported adverse events during follow up period.

Description

ketoacidosis, genital mycotic infection, urinary tract infection, Fournier's gangrene, fractures, or amputation

Time Frame

within 90 post discharge

Title

The progression of heart failure severity

Description

Time Frame

within 90 post discharge

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Rabab A EL-Gazar, MSc

Phone

01002003600

Ext

rababahmed@o6u.edu.eg

Facility Information:

Facility Name

National heart institute

City

Giza

Country

Egypt

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

bessem zarif, professor

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

The study results will be duplicated after the end of the study

IPD Sharing Time Frame

2024

Learn more about this trial

Canagliflozin in Patients With Acute Decompansted Heart Failure

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