Effects of Dapagliflozin, Semaglutide, and Their Combination in Heart Failure Patients With Prosthetic Heart Valves

NCT07610174 | Completed Phase 2

• 1 other identifier: KFSIRB200-648
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

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.

Conditions

Heart Failure; Heart Valve Prosthesis

Keywords

Heart failure; Prosthetic heart valve; Semaglutide; Dapagliflozin; SGLT2 inhibitors; GLP-1 receptor agonists; Valve surgery

Outcome Measures

Primary Outcomes (1)

• Change from Baseline in Left Ventricular Global Longitudinal Strain (LV-GLS) assessed by echocardiography

  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.

  Baseline and 12 weeks

Secondary Outcomes (4)

• Change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels.

  Baseline and 12 weeks.

• Change from baseline in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS).

  Baseline and 12 weeks.

• Change from baseline in Six-Minute Walk Test (6MWT) distance.

  Baseline and 12 weeks.

• Change from Baseline in E/e' Ratio assessed by echocardiography

  Baseline and 12 weeks

Study Arms (2)

Combination Therapy Arm

EXPERIMENTAL

Patients receive subcutaneous (s.c.) semaglutide escalated according to standard clinical protocol, initiated at a dose of 0.25 mg once weekly for 4 weeks, followed by a stepwise dose escalation every 4 weeks to 0.5 mg, then 1.0 mg if tolerated, administered in addition to a stable baseline regimen of dapagliflozin (10 mg once daily).

Drug: semaglutide; Drug: Dapagliflozin (10mg Tab)

Monotherapy Control Arm

ACTIVE COMPARATOR

Patients continue to receive standard-of-care dapagliflozin monotherapy (10 mg once daily).

Drug: Dapagliflozin (10mg Tab)

Interventions

semaglutide DRUG

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.

Combination Therapy Arm

Dapagliflozin (10mg Tab) DRUG

Sodium-glucose cotransporter 2 (SGLT2) inhibitor administered orally at a stable, standard-of-care dose of 10 mg once daily.

Combination Therapy Arm; Monotherapy Control Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Kafrelsheikh University: lead

Study Sites (1)

Kafrelsheikh univeristy hospital, Faculty of medicine, Kafrelsheikh univeristy

Kafr ash Shaykh, Kafrelsheikh Governrate, 33511, Egypt

Location

MeSH Terms

Conditions

Heart Failure

Interventions

semaglutide; dapagliflozin

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• Reda B Bastawisy, MD (Professor)

  Faculty of medicine, Kafrelshiekh university

  STUDY CHAIR

• Mohamed K Salama, MD (Assistant professor)

  Faculty of medicine, Kafrelshiekh university

  STUDY CHAIR

• Khaled E Hamada, MD (cardiology)

  Faculty of medicine, Kafrelshiekh university

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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.

Study Record Dates

• First Submitted: May 20, 2026
• First Posted: May 27, 2026
• Study Start: June 2, 2025
• Primary Completion: April 29, 2026
• Study Completion: April 29, 2026
• Last Updated: May 29, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data will be available starting 6 months after publication and will remain available for up to 2 years.
• Access Criteria: Access will be granted to qualified researchers upon reasonable request, subject to approval by the principal investigator and institutional ethics committee, and after signing a data sharing agreement.

Locations

EG (1)