Heart Failure, Heart Valve Prosthesis
Conditions
Keywords
Heart failure, Prosthetic heart valve, Semaglutide, Dapagliflozin, SGLT2 inhibitors, GLP-1 receptor agonists, Valve surgery
Brief summary
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.
Detailed description
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.
Interventions
DRUGsemaglutide
Subcutaneous (s.c.) semaglutide initiated at a dose of 0.25 mg once weekly for 4 weeks, followed by standard clinical titration (escalating every 4 weeks through 0.5 mg, then 1.0 mg, up to the maximum tolerated maintenance dose) for the duration of the study period.
Sodium-glucose cotransporter 2 (SGLT2) inhibitor administered orally at a stable, standard-of-care dose of 10 mg once daily.
Sponsors
Kafrelsheikh University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Intervention model description
This is a single-center, prospective, randomized, open-label, parallel-group trial. A total of 160 eligible patients are randomized in a strict 1:1 allocation ratio into two parallel groups: the Combination Therapy Arm (receiving oral semaglutide added to a stable baseline of 10 mg/day dapagliflozin) and the Monotherapy Control Arm (continuing on 10 mg/day dapagliflozin alone). Participants remain in their assigned treatment arm for the entire duration of the study period to compare the efficacy and safety outcomes between the two distinct therapeutic approaches.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age is at least 18 years at the time of screening. * Confirmed diagnosis of heart failure. * Documented history of surgical prosthetic heart valve replacement. * Patient is currently on a stable baseline regimen of dapagliflozin (10 mg once daily). * Patient is willing and able to provide written informed consent prior to any study-related procedures.
Exclusion criteria
* Known hypersensitivity or allergy to semaglutide, dapagliflozin, or any of their excipients. * Type 1 diabetes mellitus. * Severe renal impairment (e.g., eGFR \< 25 or 30 mL/min/1.73m², depending on your exact protocol threshold) or currently requiring dialysis. * Active pregnancy, breastfeeding, or intent to become pregnant during the 12-week study period. * Participation in another conflicting interventional clinical trial within the past 30 days.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in Left Ventricular Global Longitudinal Strain (LV-GLS) assessed by echocardiography | Baseline and 12 weeks | Left ventricular global longitudinal strain (LV-GLS) will be calculated as the average peak systolic strain using a 17-segment model derived from apical two-, three-, and four-chamber views. All studies are analyzed offline using validated software by experienced echocardiographers blinded to treatment allocation. Unit of Measure: Percentage (%), Strain is expressed as a percentage of deformation, typically a negative value where a more negative number indicates better systolic function. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. | Baseline and 12 weeks. | NT-proBNP is a well-established blood biomarker used to monitor myocardial wall stress and the severity of heart failure. Blood samples are drawn to measure the mean change in NT-proBNP levels (measured in pg/mL) from randomization baseline to the final follow-up. |
| Change from baseline in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS). | Baseline and 12 weeks. | The KCCQ-CSS is a patient-reported health status instrument specifically designed to measure the symptoms and physical limitations associated with heart failure. Scores range from 0 to 100, where lower scores reflect more severe symptoms/limitations and higher scores indicate better health status. This measure evaluates the efficacy of adding subcutaneous semaglutide to dapagliflozin compared to dapagliflozin alone by calculating the mean change in KCCQ-CSS from the randomization baseline to the final follow-up. |
| Change from baseline in Six-Minute Walk Test (6MWT) distance. | Baseline and 12 weeks. | The 6MWT evaluates objective functional capacity and exercise tolerance in heart failure patients. The test measures the maximum distance (in meters) a participant can quickly walk on a flat, hard surface in a period of 6 minutes. This endpoint calculates the mean change in walked distance from baseline to the end of the study. |
| Change from Baseline in E/e' Ratio assessed by echocardiography | Baseline and 12 weeks | Calculated using transmitral Doppler peak early filling velocity (E) in cm/s and tissue Doppler early diastolic mitral annular velocity (e') in cm/s to evaluate left ventricular diastolic filling pressure. |
Countries
Egypt
Contacts
STUDY_CHAIRReda B Bastawisy, MD (Professor)
Faculty of medicine, Kafrelshiekh university
STUDY_CHAIRMohamed K Salama, MD (Assistant professor)
Faculty of medicine, Kafrelshiekh university
STUDY_CHAIRKhaled E Hamada, MD (cardiology)
Faculty of medicine, Kafrelshiekh university
Outcome results
None listed