Effects of Dapagliflozin, Semaglutide, and Their Combination in Heart Failure Patients With Prosthetic Heart Valves (SYNCARDIA-HF)
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.
調査の概要
詳細な説明
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.
研究の種類
入学 (実際)
段階
- フェーズ2
連絡先と場所
研究場所
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Kafrelsheikh Governrate
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Kafr ash Shaykh、Kafrelsheikh Governrate、エジプト、33511
- Kafrelsheikh univeristy hospital, Faculty of medicine, Kafrelsheikh univeristy
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参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：独身
武器と介入
参加者グループ / アーム |
介入・治療 |
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実験的：Combination Therapy Arm
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).
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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.
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アクティブコンパレータ：Monotherapy Control Arm
Patients continue to receive standard-of-care dapagliflozin monotherapy (10 mg once daily).
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Sodium-glucose cotransporter 2 (SGLT2) inhibitor administered orally at a stable, standard-of-care dose of 10 mg once daily.
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Change from Baseline in Left Ventricular Global Longitudinal Strain (LV-GLS) assessed by echocardiography
時間枠：Baseline and 12 weeks
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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
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels.
時間枠：Baseline and 12 weeks.
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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.
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Baseline and 12 weeks.
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Change from baseline in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS).
時間枠：Baseline and 12 weeks.
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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.
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Baseline and 12 weeks.
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Change from baseline in Six-Minute Walk Test (6MWT) distance.
時間枠：Baseline and 12 weeks.
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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.
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Baseline and 12 weeks.
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Change from Baseline in E/e' Ratio assessed by echocardiography
時間枠：Baseline and 12 weeks
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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.
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Baseline and 12 weeks
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協力者と研究者
スポンサー
捜査官
- スタディチェア：Reda B Bastawisy, MD (Professor)、Faculty of medicine, Kafrelshiekh university
- スタディチェア：Mohamed K Salama, MD (Assistant professor)、Faculty of medicine, Kafrelshiekh university
- スタディチェア：Khaled E Hamada, MD (cardiology)、Faculty of medicine, Kafrelshiekh university
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
その他の研究ID番号
- KFSIRB200-648
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
IPD 共有時間枠
IPD 共有アクセス基準
IPD 共有サポート情報タイプ
- STUDY_PROTOCOL
- SAP
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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