Clinical trial NCT04385589: Dapagliflozin in Diabetic Patients (Type 2) With Decompensated Heart Failure
Official title: Safety and Efficacy of Adding Dapagliflozin and Furosemide in Diabetic Patients (Type 2) With Decompensated Heart Failure With Reduced Ejection Fraction (HFrEF)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Heart Failure
Lead sponsor: Assiut University
Sponsor class: OTHER
First posted: 2020-05-13
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: The study will include 100 diabetic patients type 2 patients who will be admitted to care unit with decompensated heart failure.50 patient will receive Dapagliflozin plus insulin (if needed) and Diuretics plus conventional heart failure measures ,the other group will receive insulin for control of blood sugar plus diuretics and anti-failure measures.
Primary purpose: TREATMENT

Brief summary: We hypothesize that Dapagliflozin could improve the diuretic response in diabetic patients with acute decompensated heart failure owing to its diuretic effect in addition to improvement of blood glucose level without remarkable effect on kidney function or electrolytes.

Detailed description: The study will include 100 diabetic patients type 2 patients who will be admitted to care unit with decompensated heart failure.50 patient will receive Dapagliflozin plus insulin (if needed) and Diuretics plus conventional heart failure measures ,the other group will receive insulin for control of blood sugar plus diuretics and anti-failure measures.

Inclusion Criteria:

Diabetic patient type 2 with history of chronic heart failure(HFrEF) ,there is no specified inclusion criterion with respect to heart failure etiology and/or ejection fraction.

Age more than 18 years Admission for acute decompensated heart failure The patient already on an oral loop diuretic for at least 1 month before admission, at a dose between 40 mg and 80 mg daily in the case of furosemide and an equivalent dose in the case of a different loop diuretic (20 mg of Torsemide will be considered to be equivalent to 40 mg of furosemide.

Exclusion Criteria:

1. Other etiologies of fluid overload different from heart failure.
2. Hyponatremia: Sodium level below 125mmol/l
3. Unstable patients: acute coronary syndrome, cardiogenic shock .
4. Patients requiring inotropic agents or renal dialysis.
5. Pregnancy or breastfeeding period.
6. sever hepatic disease
7. GFR (Glomerular Filtration Rate) is less than 45 mL/min/1.73 m² .
8. Patient with diabetic ketoacidosis or non ketotic hyperosmolar. Treatment arm.

The patients will receive:

Loop diuretics. Diuretics should be administered at doses sufficient to achieve optimal volume status and relieve congestion without inducing an excessively rapid reduction in intravascular volume.

furosemide will be given I.V either by continuous infusion or blouses Antifailure treatment: (Angiotensin converting enzyme inhibitors or Angiotensin II Receptor Blockers, Beta Blockers,Mineralocorticoid Receptor Antagonists, Ivabradine, or others will be individualized according to the patient condition.

Dapagliflozin:

will be given in a dose of 10mg once daily ( GFR is more than 45 mL/min/1.73 m²) .

In Mild or moderate hepatic disease: No dosage adjustment required In Severe hepatic disease: will not be used.

Insulin. Insulin therapy should be initiated if blood glucose levels is ≥180 mg/dL (10.0 mmol/L) after initiation of Dapagliflozin treatment. Once insulin therapy is started, a target glucose range of 140-180 mg/dL (7.8-10.0 mmol/L) is recommended The use of subcutaneous rapid- or short-acting insulin before meals or every 4-6 h will be given to correct hyperglycemia according to sliding scale chart.

Control arm.

The patients will be given Loop diuretics. Anti-failure treatment. Insulin.

All the patients will undergo:

1. Complete echo assessment.
2. ECG on admission and daily.
3. Monitoring:24 hours ECG ,Oxygen saturation and blood pressure monitoring. Complete blood count ,blood urea,serum creatinine,blood sugar,electrolytes ,liver function will be measured on admission
4. Blood sugar ,urea,creatinine,Na, K will be measured daily along the whole days of admission.

Follow up parameters

Diuresis :24-hour diuresis will be quantified every 24 hours (during hospitalization) from the 1st day until last day of admission.

diuretic response will be measured by weight loss and net fluid loss per mg . Changes in body weight measurements: the mean of weight lost every 24 hours and the total weight lost from baseline to the last day of hospitalization Renal function will be determined every 24 hours (during hospitalization) from the date of admission until the date of discharge.

Renal function is assessed with the serum creatinine level. Worsening renal function is defined as an increase in the serum creatinine level of more than 0.3 mg/dl at any time during hospitalization Electrolyte levels (sodium and potassium) will be determined every 24 hours (during hospitalization) from the date of admission until the date of discharge.

Electrolyte levels are assessed with the serum sodium and potassium levels. Patient-reported dyspnea : Patient-reported dyspnea is assessed every 24 hours (during hospitalization) from the date of admission until the date of discharge.

Patient-reported dyspnea will be assessed with the use five point Linker scale.

Eligibility criteria: Inclusion Criteria:

* Diabetic patient type 2 with history of chronic heart failure(HFrEF) ,there is no prespecified inclusion criterion with respect to heart failure etiology and/or ejection fraction.

Exclusion Criteria:

1. Other etiologies of fluid overload different from heart failure.
2. Hyponatremia: Sodium level below 125mmol/l
3. Unstable patients: acute coronary syndrome, cardiogenic shock .
4. Patients requiring inotropic agents or renal dialysis.
5. Pregnancy or breastfeeding period.
6. sever hepatic disease
7. GFR is less than 45 mL/min/1.73 m² .
8. Patient with diabetic ketoacidosis or non ketotic hyperosmolar.

Primary outcomes:
measure: Changes in body weight measurement (Diuresis effect.)
timeFrame: Days of admission (3-5 days)
measure: Diuresis effect.
timeFrame: Days of admission (3-5 days)
Secondary outcomes:
measure: Renal function
timeFrame: Days of admission (3-5 days)
measure: Patient-reported dyspnea will be assessed with the use five point Linker scale
timeFrame: Days of admission (3-5 days)
Other outcomes:
Locations:
city: Assuan
country: Egypt
facility: Assiut University
Study officials:
affiliation: Assiut University
name: Ayman Ibrahem, MD
role: STUDY_DIRECTOR
References:
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