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

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

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.

Study Overview

• Status: Completed
• Conditions: Acute Heart Failure
• Intervention / Treatment: Drug: Dapagliflozin 10mg Tab; Other: Placebo

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 Type: Interventional
• Enrollment (Actual): 87
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Egypt
  • Mansoura, Egypt, 35516
    • Noha Mansour

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. 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.

2. Randomized within 24 hours of hospitalization for AHF
3. Planned use of IV loop diuretic therapy during current hospitalization
4. Estimated glomerular filtration rate (eGFR) of at least 30 ml/min/1.73m2 by the MDRD equation
5. For diabetic patients, history of type 2 diabetes or a new hemoglobin A1c 6.5% on admission.

Exclusion Criteria:

1. Type 1 diabetes mellitus.
2. Dyspnea primarily due to non-cardiac causes.
3. Cardiogenic shock.
4. Acute coronary syndrome within 30 days prior to randomization.
5. Planned or recent percutaneous or surgical coronary intervention within 30 days prior to randomization.
6. Signs of ketoacidosis and/or hyperosmolar hyperglycemic syndrome (pH>7.30 and glucose >15 mmol/L and HCO3>18 mmol/L).
7. Pregnant or nursing (lactating) women.
8. Heart failure due to drug toxicity
9. Adherence to medication less than 95%

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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
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
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

Collaborators and Investigators

• Sponsor: 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 record dates

Study Major Dates

• Study Start (Actual): April 25, 2022
• Primary Completion (Actual): May 1, 2023
• Study Completion (Actual): July 1, 2023

Study Registration Dates

• First Submitted: November 12, 2021
• First Submitted That Met QC Criteria: June 2, 2022
• First Posted (Actual): June 6, 2022

Study Record Updates

• Last Update Posted (Actual): August 4, 2023
• Last Update Submitted That Met QC Criteria: August 1, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Diabetic and non diabetic
• 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; Dapagliflozin
• Other Study ID Numbers: 2022-61

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No