Effect of Dapagliflozin in Patients With Acute Heart Failure (DAPA-RESPONSE-AHF)
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2/Phase 3 |
Detailed Description
Dapagliflozin has been shown to reduce the cardiovascular death and worsening HF in patients with reduced ejection fraction and is likely to be incorporated as a part of guideline-directed medical therapy in patients with established chronic heart failure, either with or without diabetes. Based on both the promising pharmacological and safety profile of dapagliflozin we hypothesized that it might exerts positive effects during hospitalization with acute HF when compared to structured usual care. Clinical evidence from randomized trials in AHF hospitalized patient are so far lacking. The aim of present study is to investigate the efficacy and safety of early initiation of dapagliflozin in those patients.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Dapagliflozine 10mg
|
Drug: Dapagliflozin 10mg Tab
patients will receive once daily dapagliflozin 10 mg orally in addition to protocol directed loop diuretic therapy.
|
| Placebo Comparator: Placebo
|
Other: Placebo
patients will receive protocol directed loop diuretic therapy and standard care.
|
Outcome Measures
Primary Outcome Measures
- Change in dyspnea ( Visual analogue scale) (VAS) [From baseline to day 4]
• 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
Secondary Outcome Measures
- Incidence of worsening hear failure (HF) [60 days from discharge]
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.
- All-cause death [30 days from discharge]
Difference in all cause mortality rate
- All-cause death [60 days from discharge]
Difference in all cause mortality rate
- Hospital readmission [30 days from discharge]
Difference between groups in rate of readmission after discharge for heart failure related reason
- Hospital readmission [60 days from discharge]
Difference between groups in rate of readmission after discharge for heart failure reason
- Urinary sodium 2 hours post randomization [2 Hours]
Difference in sodium execrated in urine (mmol/L) after 2 hours between study groups
- Difference in serum levels of congestion biomarkers [4 days post-randomization]
Difference in serum levels of Nt-ProBNP 4 days post-randomization
Eligibility Criteria
Criteria
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%
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Noha Mansour | Mansoura | Egypt | 35516 |
Sponsors and Collaborators
- Mansoura University
Investigators
- Principal Investigator: Noha Mansour, PhD, Department of Clinical Pharmacy & Pharmacy Practice, Faculty of Pharmacy, University of Mansoura
- Principal Investigator: Moheb Magdy Mouris, MD, Department of Cardiology, Faculty of Medicine, University of Mansoura
- Study Chair: Mohamed El-Husseiny Shams, Proffesor, Department of Clinical Pharmacy & Pharmacy Practice, Faculty of Pharmacy, University of Mansoura
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2022-61