A Prospective, Randomized, Open-Label, Blinded-Endpoint, Parallel-Group, Phase IIb Proof-of-Concept Clinical Trial of Semaglutide Added to Dapagliflozin Versus Dapagliflozin Monotherapy in Patients With Heart Failure and Previous Surgical Prosthetic Valve Replacement
A Prospective, Randomized, Open-Label, Blinded-Endpoint, Parallel-Group, Phase IIb Proof-of-Concept Clinical Trial of Semaglutide Added to Dapagliflozin Versus Dapagliflozin Monotherapy in Patients With Heart Failure and Previous Surgical Prosthetic Valve Replacement
This study evaluates whether adding a medication called semaglutide to an existing treatment of dapagliflozin provides better outcomes for patients with heart failure who have previously undergone surgical heart valve replacement.
Dapagliflozin is already a standard treatment for managing heart failure symptoms. However, many heart failure patients-especially those who have had surgical prosthetic valve replacements-continue to experience persistent symptoms, fluid retention, and a decline in their quality of life. This trial aims to investigate whether combining dapagliflozin with semaglutide (a medication widely used for metabolic health and weight management) can safely offer additional clinical benefits.
Participants in this study are divided into two groups:
Group 1 (Combination Therapy): Receives semaglutide added to their standard dapagliflozin routine.
Group 2 (Monotherapy Control): Continues receiving dapagliflozin alone.
Researchers will monitor both groups over a set treatment period to compare changes in heart function, symptom management, fluid control, and overall quality of life to see if the combination approach is more effective than standard treatment.
This is a single-center, prospective, randomized, open-label, blinded-endpoint (PROBE), parallel-group, Phase IIb proof-of-concept clinical trial conducted at Kafrelsheikh University Hospital. The study evaluates the clinical efficacy, safety, and tolerability of combining the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide with the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin, compared against dapagliflozin monotherapy, in patients presenting with heart failure (HF) who have a history of surgical prosthetic heart valve replacement.
A total of 160 eligible patients are randomized in a strict 1:1 allocation ratio to one of two parallel treatment arms:
Combination Therapy Arm: Patients receive oral semaglutide escalated according to standard clinical protocol, administered in addition to a stable baseline regimen of dapagliflozin (10 mg once daily).
Monotherapy Control Arm: Patients continue to receive standard-of-care dapagliflozin monotherapy (10 mg once daily).
The primary objective is to determine if dual metabolic pathway modulation via combined SGLT2 inhibition and GLP-1 receptor agonism provides superior optimization of cardiovascular outcomes over SGLT2 inhibition alone. Key secondary and surrogate clinical outcomes assessed across the treatment duration include changes in New York Heart Association (NYHA) functional class, evaluation of fluid retention and diuretic requirements, echocardiographic parameters evaluating cardiac structure and function, and standardized quality-of-life assessment scores. Safety and tolerability profiles-including adverse event rates and systemic hemodynamic responses-will be rigorously monitored across both treatment cohorts.
Inclusion Criteria:
Exclusion Criteria: