- ICH GCP
- Registr klinických studií v USA
- Klinická studie NCT01800968
Functional Impact of GLP-1 for Heart Failure Treatment (FIGHT) (FIGHT)
Functional Impact of GLP-1 for Heart Failure Treatment
Přehled studie
Postavení
Podmínky
Intervence / Léčba
Detailní popis
Hospitalization for AHFS identifies individuals at increased risk of death and re-hospitalization following discharge. This increased risk justifies intervention with novel therapy during the vulnerable post-discharge period to enhance clinical stability and prevent early HF mortality and readmissions.
As heart failure (HF) progresses, impairments in metabolism render the heart substrate constrained, limiting cardiac metabolism. Glucagon-like peptide-1 (GLP-1) is a naturally occurring incretin peptide that enhances cellular glucose uptake by stimulating insulin secretion and insulin sensitivity in target tissues. Preclinical and early-phase clinical data support GLP-1 as an effective therapy for advanced HF while use of GLP-1 receptor agonists in large numbers of patients with diabetes reveal a good safety profile and reductions in adverse cardiac outcomes.
Typ studie
Zápis (Aktuální)
Fáze
- Fáze 2
Kontakty a umístění
Studijní místa
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Delaware
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Newark, Delaware, Spojené státy, 19718
- Christiana Care Health Services
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Georgia
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Atlanta, Georgia, Spojené státy, 30322
- Emory University School of Medicine
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Illinois
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Chicago, Illinois, Spojené státy, 60611
- Northwestern University
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Maryland
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Baltimore, Maryland, Spojené státy, 21287
- Johns Hopkins Hospital
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Massachusetts
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Boston, Massachusetts, Spojené státy, 02115
- Brigham and Women's Hospital
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Boston, Massachusetts, Spojené státy, 02114
- Massachusetts General Hospital
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Boston, Massachusetts, Spojené státy, 02111
- Tufts Medical Center
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West Roxbury, Massachusetts, Spojené státy, 02132
- Boston VA Healtcare System
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Minnesota
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Rochester, Minnesota, Spojené státy, 55905
- Mayo Clinic
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Missouri
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St. Louis, Missouri, Spojené státy, 63110
- Washington University
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St. Louis, Missouri, Spojené státy, 63117
- Saint Louis University Hospital
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North Carolina
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Durham, North Carolina, Spojené státy, 27705
- Duke University
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Lumberton, North Carolina, Spojené státy, 28538
- Southeast Regional Medical Center
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Ohio
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Cleveland, Ohio, Spojené státy, 44195
- Cleveland Clinic
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Cleveland, Ohio, Spojené státy, 44109
- Metro Health System
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Cleveland, Ohio, Spojené státy, 44106
- University Hospitals- Case Medical Center
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Pennsylvania
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Lancaster, Pennsylvania, Spojené státy, 17603
- Lancaster Heart and Stroke Foundation
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Philadelphia, Pennsylvania, Spojené státy, 19107
- Jefferson Medical College
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Philadelphia, Pennsylvania, Spojené státy, 19140
- Temple University Hospital
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Philadelphia, Pennsylvania, Spojené státy, 19104
- University of Pennsylvaina
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Texas
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Houston, Texas, Spojené státy, 77030
- Michael DeBakey VA Medical Center
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Utah
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Murray, Utah, Spojené státy, 84157
- Intermountain Medical Center
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Salt Lake City, Utah, Spojené státy, 84132
- University Of Utah School Of Medicine
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Salt Lake City, Utah, Spojené státy, 84132
- Utah VA Medical Center
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Vermont
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Burlington, Vermont, Spojené státy, 05401
- The University of Vermont- Fletcher Allen Health Care
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
Inclusion Criteria:
- Age ≥ 18 years
- AHFS as defined by the presence of at least 1 symptom (dyspnea, orthopnea, or edema) AND 1 sign (rales on auscultation, peripheral edema, ascites, pulmonary vascular congestion on chest radiography)
- AHFS is the primary cause of hospitalization
- Prior clinical diagnosis of HF
- Left Ventricular Ejection Fraction(LVEF) ≤ 40% during the preceding 3 months (if no echo within the preceding 3 months, an LVEF ≤ 30% during the preceding three years is acceptable)
- On evidence-based medication for HF (including beta-blocker and ACE-inhibitor/ARB) or previously deemed intolerant
- Use of at least 80 mg or furosemide total daily dose (or equivalent) prior to admission for AHFS (a lower dose of a loop diuretic combined with a thiazide will count as an "equivalent")
- Willingness to provide informed consent
Exclusion Criteria:
- AHFS due to acute myocarditis or acute Myocardial Infarction
- Ongoing hemodynamically significant arrhythmias contributing to HF decompensation
- Inotrope, intra-aortic balloon pump (IABP) or other mechanical circulatory support use at the time of consent. Prior use will not exclude a patient.
- Current or planned left ventricular assist device therapy in next 180 days
- United Network for Organ Sharing status 1A or 1B
- B-type natriuretic peptide(BNP)< 250 or NT-proBNP<1,000 (Not required per protocol but if available and too low would be an exclusion; within 48 hours of consent)
- Hemoglobin (Hgb) < 8.0 g/dl
- Glomerular filtration rate(GFR) < 20 ml/min/1.73 m2 within 48 hours of consent
- Systolic blood pressure < 80 mmHg at consent
- Resting Heart Rate > 110 at consent
- Acute coronary syndrome within 4 weeks as defined by electrocardiographic (ECG) changes and biomarkers of myocardial necrosis (e.g. troponin) in an appropriate clinical setting (chest discomfort or anginal equivalent)
- Percutaneous Coronary Intervention, coronary artery bypass grafting or new biventricular pacing within past 4 weeks
- Primary hypertrophic cardiomyopathy
- Infiltrative cardiomyopathy
- Constrictive pericarditis or tamponade
- Complex congenital heart disease
- Non-cardiac pulmonary edema
- More than moderate aortic or mitral stenosis
- Intrinsic (prolapse, rheumatic) valve disease with severe mitral, aortic or tricuspid regurgitation
- Sepsis, active infection (excluding cystitis) or other comorbidity driving the HF decompensation
- Acute or chronic severe liver disease as evidenced by any of the following: encephalopathy, variceal bleeding, International Normalized Ration (INR) > 1.7 in the absence of anticoagulation treatment
- Terminal illness (other than HF) with expected survival of less than 1 year
- Previous adverse reaction to the study drug
- Receipt of any investigational product in the previous 30 days.
- Enrollment or planned enrollment in another randomized therapeutic clinical trial in next 6 months.
- Inability to comply with planned study procedures
- Pregnancy or breastfeeding mothers
- Women of reproductive age not on adequate contraception
- History of acute or chronic pancreatitis
- History of symptomatic gastroparesis
- Familial or personal history of medullary thyroid cancer or multiple endocrine neoplasia type-2 (MEN2)
- Prior weight-loss surgery (i.e., Roux-en-Y gastric bypass) or other gastric surgery associated with increased endogenous GLP-1 production
- Prior or ongoing treatment with GLP-1 receptor agonists
- Ongoing treatment with dipeptidyl peptide-IV inhibitors (1 week washout required)
- Ongoing treatment with thiazolidinedione
- Oxygen-dependent chronic obstructive pulmonary disease
- Diabetic patients with history of 2 or more severe hypoglycemia, Diabetic Ketoacidosis(DKA) or hyperglycemic, hyperosmotic nonketotic coma in the preceding 12 months.
- Diagnosis of Type 1 Diabetes Mellitus
40. If diabetic, inadequate glycemic control with glucose level > 300 mg/dL within 24 hours of randomization
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Dvojnásobek
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
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Aktivní komparátor: Liraglutide
Increasing dose from 0.6mg, 1.2mg to 1.8mg SQ daily.
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Active Drug
Ostatní jména:
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Komparátor placeba: Placebo
Placebo dose increasing from 0.6mg, 1.2mg to 1.8 mg SQ daily.
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Placebo
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
---|---|---|
Global Ranking of Predefined Events
Časové okno: Randomization to 180 days
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A rank score based on time to death, time to adjudicated heart failure hospitalization, and time-averaged proportional change in NTproBNP through d180.
For patients that died, the patient with the shortest time from randomization to death is assigned rank 1, the second shortest time is assigned rank 2, etc.
The patient with the longest time from randomization to death is assigned rank X.
For patients that did not die but had a heart failure hospitalization, the patient with the shortest time from randomization to re-admission is assigned rank X+1 and the patient with the longest time from randomization to heart failure hospitalization is assigned rank Y.
For patients that did not die or have a heart failure hospitalization, increases in time-averaged proportional change in NTproBNP indicate a worse result and the largest increase is assigned rank Y+1.
The patient with the largest decrease is assigned rank N, where N is the sample size.
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Randomization to 180 days
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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
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Change in Left Ventricular End-Diastolic Volume Index
Časové okno: Baseline to 180 days
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Change in Left Ventricular End-Diastolic Volume Index from baseline to 180 days.
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Baseline to 180 days
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Change in Left Ventricular End-systolic Volume Index
Časové okno: Baseline to 180 days
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Change in left ventricular end-systolic volume index from baseline to day 180.
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Baseline to 180 days
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Change in Left Ventricular Ejection Fraction
Časové okno: Baseline to 180 days
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Change in left ventricular ejection fraction from baseline to day 180
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Baseline to 180 days
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Change in Medial Filling Pressure
Časové okno: Baseline to 180 days
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Change in medial filling pressure baseline to day 180.
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Baseline to 180 days
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Change in Lateral Filling Pressure
Časové okno: Baseline to 180 days
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Change in lateral filling pressure baseline to day 180.
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Baseline to 180 days
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Change in 6 Minute Walk Distance
Časové okno: Baseline to day 30
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Change in 6 minute walk distance baseline to day 30
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Baseline to day 30
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Change in 6 Minute Walk Distance
Časové okno: Baseline to 90 days
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Change in 6 minute walk distance baseline to 90 days.
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Baseline to 90 days
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Change in 6 Minute Walk Distance
Časové okno: Baseline to 180 days
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Change in 6 minute walk distance baseline to 180 days.
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Baseline to 180 days
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Change in Clinical Summary Score Using the Kansas City Cardiomyopathy Questionnaire (KCCQ)
Časové okno: Baseline to 30 days
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Change in clinical summary score using the Kansas City Cardiomyopathy Questionnaire (KCCQ) baseline to 30 days.
The Kansas City Cardiomyopathy Questionnaire is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life.In the KCCQ, an overall summary score can be derived from the physical function, symptom (frequency and severity), social function and quality of life domains.
For each domain, the validity, reproducibility, responsiveness and interpretability have been independently established.
Each question is answered by the subject on a 6 point scale (Extremely limited, quite a bit limited, moderately limited, slightly limited, not at all limited, Limited for other reasons or did not do this activity).Scores are transformed to a range of 0-100, in which higher scores reflect better health status.
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Baseline to 30 days
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Change in Clinical Summary Score Using the Kansas City Cardiomyopathy Questionnaire (KCCQ)
Časové okno: Baseline to 90 days
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Change in clinical summary score using the Kansas City Cardiomyopathy Questionnaire (KCCQ) baseline to 90 days.The Kansas City Cardiomyopathy Questionnaire is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life.In the KCCQ, an overall summary score can be derived from the physical function, symptom (frequency and severity), social function and quality of life domains.
For each domain, the validity, reproducibility, responsiveness and interpretability have been independently established.
Each question is answered by the subject on a 6 point scale (Extremely limited, quite a bit limited, moderately limited, slightly limited, not at all limited, Limited for other reasons or did not do this activity).Scores are transformed to a range of 0-100, in which higher scores reflect better health status.
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Baseline to 90 days
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Change in Clinical Summary Score Using the Kansas City Cardiomyopathy Questionnaire (KCCQ)
Časové okno: Baseline to day 180
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Change in clinical summary score using the Kansas City Cardiomyopathy Questionnaire (KCCQ) from baseline to day 180.The Kansas City Cardiomyopathy Questionnaire is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life.In the KCCQ, an overall summary score can be derived from the physical function, symptom (frequency and severity), social function and quality of life domains.
For each domain, the validity, reproducibility, responsiveness and interpretability have been independently established.
Each question is answered by the subject on a 6 point scale (Extremely limited, quite a bit limited, moderately limited, slightly limited, not at all limited, Limited for other reasons or did not do this activity).Scores are transformed to a range of 0-100, in which higher scores reflect better health status.
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Baseline to day 180
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Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score
Časové okno: Baseline to 30 days
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Kansas City Cardiomyopathy Questionnaire (KCCQ) change in overall summary score baseline to 30 days.The Kansas City Cardiomyopathy Questionnaire is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life.In the KCCQ, an overall summary score can be derived from the physical function, symptom (frequency and severity), social function and quality of life domains.
For each domain, the validity, reproducibility, responsiveness and interpretability have been independently established.
Each question is answered by the subject on a 6 point scale (Extremely limited, quite a bit limited, moderately limited, slightly limited, not at all limited, Limited for other reasons or did not do this activity).Scores are transformed to a range of 0-100, in which higher scores reflect better health status.
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Baseline to 30 days
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Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score
Časové okno: Baseline to 90 days
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Kansas City Cardiomyopathy Questionnaire (KCCQ) change in overall summary score baseline to 90 days.The Kansas City Cardiomyopathy Questionnaire is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life.In the KCCQ, an overall summary score can be derived from the physical function, symptom (frequency and severity), social function and quality of life domains.
For each domain, the validity, reproducibility, responsiveness and interpretability have been independently established.
Each question is answered by the subject on a 6 point scale (Extremely limited, quite a bit limited, moderately limited, slightly limited, not at all limited, Limited for other reasons or did not do this activity).Scores are transformed to a range of 0-100, in which higher scores reflect better health status.
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Baseline to 90 days
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Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score.
Časové okno: Baseline to 180 days
|
Kansas City Cardiomyopathy Questionnaire (KCCQ) change in overall summary score baseline to 180 days.The Kansas City Cardiomyopathy Questionnaire is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life.In the KCCQ, an overall summary score can be derived from the physical function, symptom (frequency and severity), social function and quality of life domains.
For each domain, the validity, reproducibility, responsiveness and interpretability have been independently established.
Each question is answered by the subject on a 6 point scale (Extremely limited, quite a bit limited, moderately limited, slightly limited, not at all limited, Limited for other reasons or did not do this activity).Scores are transformed to a range of 0-100, in which higher scores reflect better health status.
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Baseline to 180 days
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Individual Component of the Primary Endpoint- Mortality
Časové okno: Randomization to 180 days
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Individual component of the primary endpoint of mortality at 180 days after randomization
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Randomization to 180 days
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Individual Component of the Primary Endpoint- Heart Failure Hospitalization
Časové okno: Randomization to 180 days
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Individual component of the primary endpoint- Heart Failure hospitalization from randomization to 180 days
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Randomization to 180 days
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Individual Component of the Primary Endpoint- Time-averaged Proportional Change in NT-proBNP
Časové okno: Baseline to 180 days
|
Individual component of the primary endpoint- time-averaged proportional change in NT-proBNP from baseline to 180 days
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Baseline to 180 days
|
Global Ranking of Predefined Events
Časové okno: Baseline to 180 days
|
A rank score based on time to death, time to adjudicated heart failure hospitalization, time to emergency department visit and time-averaged proportional change in NTproBNP through d180.
See Outcome Measure 1 for a general description of the outcome derivation.
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Baseline to 180 days
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Spolupracovníci a vyšetřovatelé
Sponzor
Spolupracovníci
Vyšetřovatelé
- Studijní židle: Eugene Bruanwald, MD, Harvard University
Publikace a užitečné odkazy
Obecné publikace
- Lerman JB, Giamberardino SN, Hernandez AF, Felker GM, Shah SH, McGarrah RW. Plasma metabolites associated with functional and clinical outcomes in heart failure with reduced ejection fraction with and without type 2 diabetes. Sci Rep. 2022 Jun 2;12(1):9183. doi: 10.1038/s41598-022-12973-0.
- Redouane B, Greene SJ, Fudim M, Vaduganathan M, Ambrosy AP, Sun JL, DeVore AD, McNulty SE, Mentz RJ, Hernandez AF, Felker GM, Cooper LB, Borlaug BA, Velazquez EJ, Margulies KB, Sharma A. Effects of Liraglutide on Worsening Renal Function Among Patients With Heart Failure With Reduced Ejection Fraction: Insights From the FIGHT Trial. Circ Heart Fail. 2020 May;13(5):e006758. doi: 10.1161/CIRCHEARTFAILURE.119.006758. Epub 2020 May 4.
- Sharma A, Ambrosy AP, DeVore AD, Margulies KB, McNulty SE, Mentz RJ, Hernandez AF, Michael Felker G, Cooper LB, Lala A, Vader J, Groake JD, Borlaug BA, Velazquez EJ. Liraglutide and weight loss among patients with advanced heart failure and a reduced ejection fraction: insights from the FIGHT trial. ESC Heart Fail. 2018 Dec;5(6):1035-1043. doi: 10.1002/ehf2.12334. Epub 2018 Aug 17.
- Margulies KB, Hernandez AF, Redfield MM, Givertz MM, Oliveira GH, Cole R, Mann DL, Whellan DJ, Kiernan MS, Felker GM, McNulty SE, Anstrom KJ, Shah MR, Braunwald E, Cappola TP; NHLBI Heart Failure Clinical Research Network. Effects of Liraglutide on Clinical Stability Among Patients With Advanced Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial. JAMA. 2016 Aug 2;316(5):500-8. doi: 10.1001/jama.2016.10260.
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia
Primární dokončení (Aktuální)
Dokončení studie (Aktuální)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Odhad)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Další relevantní podmínky MeSH
Další identifikační čísla studie
- Pro00042633
- 5U10HL084904-09 (Grant/smlouva NIH USA)
Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .
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