Effect of Dapagliflozin in Patients With Acute Heart Failure (DAPA-RESPONSE-AHF)

Study Overview
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Brief Summary
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Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor (SGLT2i), increases natriuresis alone and synergistically when combined with loop diuretics in patients with AHF without increasing renin angiotensin- aldosterone activity. Thus, adding SGLT2i to the standard loop diuretic therapy might confer additional decongestive and natriuretic benefits while avoiding the adverse electrolyte abnormalities and neurohormonal activation associated with other diuretic combination. These potential benefits may help with improved clinical outcomes, but clinical evidence is still lacking.

Official Title
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Effect of Adjuvant Dapagliflozin on Improving the Treatment of Congestion in Patients With Acute Heart Failure (DAPA-RESPONSE-AHF)

Conditions
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Acute Heart Failure

Intervention / Treatment
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* Drug: Dapagliflozin 10mg Tab
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults aged 18 years or older who are hospitalized for hypervolemic AHF, with evidence of congestion defined as either: * 2 of the following signs or symptoms: peripheral edema, ascites, jugular venous pressure > 10mmHg, orthopnea, paroxysmal nocturnal dyspnea, 5-pound weight gain, or signs of congestion on chest x-ray or lung ultrasound. OR *If pulmonary artery catheterization is available, a pulmonary capillary wedge pressure greater than 19 mmHg plus a systemic physical exam finding of hypervolemia from the list above. Randomized within 24 hours of hospitalization for AHF Planned use of IV loop diuretic therapy during current hospitalization Estimated glomerular filtration rate (eGFR) of at least 30 ml/min/1.73m2 by the MDRD equation For diabetic patients, history of type 2 diabetes or a new hemoglobin A1c 6.5% on admission. Exclusion Criteria: Type 1 diabetes mellitus. Dyspnea primarily due to non-cardiac causes. Cardiogenic shock. Acute coronary syndrome within 30 days prior to randomization. Planned or recent percutaneous or surgical coronary intervention within 30 days prior to randomization. Signs of ketoacidosis and/or hyperosmolar hyperglycemic syndrome (pH>7.30 and glucose >15 mmol/L and HCO3>18 mmol/L). Pregnant or nursing (lactating) women. Heart failure due to drug toxicity Adherence to medication less than 95%

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dapagliflozine 10mg<br> | Drug: Dapagliflozin 10mg Tab<br>* patients will receive once daily dapagliflozin 10 mg orally in addition to standard care<br>|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* patients will receive placebo and standard care.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in dyspnea ( Visual analogue scale) (VAS) | • Comparing the area under the curve (AUC) of change in VAS dyspnea score. To do so, individual changes in VAS score will be visualized as a curve where the x-axis shows study day baseline to day 5, and y-axis shows VAS score. the overall VAS AUC score (mm × h) will be compared across treatment groups | From baseline to day 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of worsening heart failure (HF) | Defined as worsening signs and/or symptoms of HF that require IV inotropic therapy or admission to an intensive care unit or mechanical ventilatory, renal or circulatory support. | From the date of randomization until discharge or end of treatment, whichever came first, assessed up to 30 days | 
| All-cause death | Difference in all cause mortality rate | 30 days from discharge | 
| All-cause death | Difference in all cause mortality rate | 60 days from discharge | 
| Hospital readmission | Difference between groups in rate of readmission after discharge for heart failure related reason | 30 days from discharge | 
| Hospital readmission | Difference between groups in rate of readmission after discharge for heart failure reason | 60 days from discharge | 
| Urinary sodium 2 hours post randomization | Difference in sodium execrated in urine (mmol/L) after 2 hours between study groups | 2 Hours | 
| Difference in serum levels of congestion biomarkers | Difference in serum levels of Nt-ProBNP 4 days post-randomization | 4 days post-randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetic and non diabetic