Early Treatment With a Sodium-glucose Co-transporter 2 Inhibitor in High-risk Patients With Acute Heart Failure
- Registration Number
- NCT05392764
- Lead Sponsor
- Juntendo University
- Brief Summary
The EMPA-AHF trial is a multicentre, randomized, double-blind, placebo-controlled trial designed to evaluate the efficacy and safety of early initiation of once-daily oral empagliflozin 10 mg in patients hospitalized for patients with acute heart failure (AHF) who are at a high risk of adverse events.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 524
Patients who meet the below inclusion criteria will be randomized within 12 h after presentation to the hospital
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Age of ≥20 and <90 years
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Hospitalized with a diagnosis of acute heart failure, requiring intravenous loop diuretic therapy, and with all of the following characteristics:
i. Dyspnoea at rest or induced by slight exertion ii. At least two of the following findings: jugular venous distention, pulmonary rales, lower leg edema, and pulmonary congestion on chest X-ray iii. If the patient has a sinus rhythm at the time of admission, BNP ≥350 pg/mL or NT-proBNP ≥1400 pg/mL; if the patient has atrial fibrillation at the time of admission, BNP ≥500 pg/mL or NT-proBNP ≥2000 pg/mL. For patients taking an angiotensin receptor neprilysin inhibitor, only the reference value for NT-proBNP will be applicable.
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At least one of the following characteristics:
i. eGFR <60 mL/min/1.73m2, as calculated using the CKD Epidemiology Collaboration for JapaneseModification of Diet in Renal Disease formula ii. Already taking ≥40 mg of oral furosemide during the period before hospitalization. For patients on loop diuretics other than furosemide, the following conversion should be used: oral furosemide 20 mg = oral azosemide 30 mg = oral torasemide 5 mg.
iii. Urine output of <300 mL during the 2 h following an appropriate dose of intravenous furosemide administered after hospitalization. An appropriate dose of intravenous furosemide is 20 mg for patients who have not been taking furosemide regularly before hospitalization and is the same as, or greater than, the daily oral dose for patients who have been taking furosemide regularly before hospitalization.
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Provided written consent to participate in the study
- eGFR <20 mL/min/1.73m2 at the time of admission
- Already taking an SGLT2i within 3 months prior to hospitalization
- Type 1 diabetes mellitus
- Systolic blood pressure <90 mmHg
- Expected to newly require treatment with thiazide, tolvaptan, or carperitide within 48 hours of study drug administration
- Main cause of acute heart failure hospitalization is not fluid retention (e.g., persistent ventricular tachycardia, persistent atrial fibrillation/atrial flutter with a ventricular response rate of ≥130 bpm, persistent bradycardia with a ventricular response rate of <45 bpm, an infection, severe anemia, and an acute exacerbation of COPD)
- Acute coronary syndrome, pulmonary thromboembolism, or a cerebrovascular accident is the main cause of the present hospitalization.
- At risk of ketoacidosis or hyperosmolar hyperglycaemia
- On dialysis, including peritoneal dialysis, or the initiation of dialysis during hospitalization is planned
- Pregnant or lactating women
- Underwent the following therapeutic interventions within 30 days: cardiovascular surgery (e.g., coronary artery bypass grafting, surgery for valvular heart disease, transcatheter aortic valve implantation, percutaneous coronary intervention, percutaneous edge-to-edge mitral valve repair, and other types of surgery at the investigator's discretion) and implantation of an implantable defibrillator, cardiac resynchronization therapy defibrillator, or implantable ventricular-assist device
- A diagnosis of acute coronary syndrome, cerebral infarction, or transient ischemic attack made within 90 days
- Ventricular tachycardia with syncope within 90 days
- Heart transplant recipient or listed for heart transplantation and expected to undergo transplantation during the present treatment; implanted with an implantable ventricular-assist device or expected to require an implantable ventricular-assist device during the present treatment; or expected to switch to palliative care
- Intubated at the time of screening or expected to require intubation within within 48 hours of study drug administration
- Severe valvular heart disease expected to be treated with thoracostomy or catheterization (a reason to exclude secondary mitral or tricuspid regurgitation due to reduced cardiac function does not exist, except for the absence of a plan to perform cardiac surgery or therapeutic catheterization)
- A diagnosis of secondary cardiomyopathy such as amyloidosis, cardiac sarcoidosis, hemochromatosis, Fabry disease, and muscular dystrophy. Heart failure due to takotsubo cardiomyopathy, obstructive hypertrophic cardiomyopathy, complex congenital heart disease (as determined by the investigator), or pericardial constriction.
- A diagnosis of peripartum cardiomyopathy made within 6 months
- Active myocarditis
- Presence of uncontrolled thyroid disease
- Acute cardiac structural abnormalities (e.g., acute mitral regurgitation due to ruptured chordae tendineae)
- Symptomatic bradycardia or complete atrioventricular block, being treated with a temporary pacemaker implantation at the time of admission, or expected to require a temporary pacemaker implantation in the future. Patients who have already been treated with a permanent pacemaker implantation do not meet the exclusion criteria.
- Serious liver disorder (an increase in AST, ALT, or ALP level ≥3 times the upper limit of normal) or cirrhosis with varices or other findings suggestive of portal hypertension
- Alcohol use disorder of at least mild severity according to the DSM-V
- A diagnosis of active malignancy or suspected active malignancy made within 2 years
- Coexisting diseases other than heart failure with an expected survival prognosis of ≤1 year
- Participation in a clinical study of another drug 30 days before hospitalization
- Patients considered to require fasting at screening.
- Other conditions likely to interfere with the patient's safety or compliance with the protocol
- Other patients who are considered unsuitable by the principal investigator or other investigators
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Empagliflozin Empagliflozin 10 MG Patients will be randomized 1:1 to either empagliflozin or placebo. Placebo Placebo Placebo matching empagliflozin
- Primary Outcome Measures
Name Time Method A hierarchical composite endpoint consisting of death within 90 days, heart failure rehospitalization within 90 days, WHF during hospitalization, and urine output up to 48 hours after treatment initiation, assessed by the win ratio Up to 90 days WHF, worsening heart failure
- Secondary Outcome Measures
Name Time Method A hierarchical composite endpoint consisting of death within 90 days, heart failure readmission within 90 days, and WHF during hospitalization Up to 90 days WHF, worsening heart failure
A composite endpoint consisting of WHF during hospitalization, death, heart failure rehospitalization, urgent visit for WHF, intensification of diuretic therapy, and worsening NYHA class within 90 days Up to 90 days WHF, worsening heart failure
Change in NT-proBNP from randomization to 48 hours Evaluated at 48 hours after randomization Diuretic response, calculated as urine output achieved by loop diuretics (40 mg intravenous furosemide-equivalent dose) at 48 h after treatment initiation Evaluated at 48 hours after randomization Time to hemodynamic stabilization during index hospitalization During index hospitalization Urine output during the 48 h after randomization Evaluated at 48 hours after randomization Cardiovascular death Up to 90 days Change in the visual analog scale score for dyspnea from after randomization to 24 and 48 h Evaluated at 24 and 48 hours after randomization The scores range from 0 to 100, with 100 being the best possible score.
Composite of renal replacement therapy, renal transplantation, eGFR <15 mL/min/1.73m2, ≥50% decrease in eGFR compared to the first sample or a ≥2-fold increase in creatinine level compared to the first sample within 90 days of randomization Up to 90 days Improvement in KCCQ-TSS of ≥5 points from randomization to 30 and 90 days after treatment initiation Up to 90 days KCCQ-TSS, Kansas City Cardiomyopathy Questionnaire - Total Symptom Score. The scores range from 0 to 100, with 100 being the best possible score.
Trend in eGFR after randomization to 24 h, 48 h, 30 days, and 90 days Up to 90 days Re-worsening of heart failure during index hospitalization During index hospitalization Death Up to 90 days Heart failure rehospitalization Up to 90 days Change in high sensitivity cardiac troponin T Evaluated at 48 hours after randomization Change in the KCCQ-TSS after randomization to 30 and 90 days Up to 90 days KCCQ-TSS, Kansas City Cardiomyopathy Questionnaire - Total Symptom Score. The scores range from 0 to 100, with 100 being the best possible score.
Trial Locations
- Locations (61)
Mitsui Memorial Hospital
🇯🇵Chiyoda, Tokyo, Japan
International University of Health and Welfare Mita Hospital
🇯🇵Minato, Tokyo, Japan
Nishiarai Hospital
🇯🇵Adachi, Tokyo, Japan
Sakakibara Heart Institute
🇯🇵Fuchū, Tokyo, Japan
Toranomon Hospital
🇯🇵Minato, Tokyo, Japan
Tokyo Women's Medical University Hospital
🇯🇵Shinjuku, Tokyo, Japan
Tokyo Medical University Hachioji Medical Center
🇯🇵Hachiōji, Tokyo, Japan
Anjo Kosei Hospital
🇯🇵Anjo, Aichi, Japan
Juntendo University Urayasu Hospital
🇯🇵Urayasu, Chiba, Japan
Aichi Medical University Hospital
🇯🇵Nagakute, Aichi, Japan
Gifu University Graduate school of Medicine
🇯🇵Gifu, Japan
Chikamori Hospital
🇯🇵Kochi, Japan
Tokyo General Hospital
🇯🇵Tokyo, Japan
Hiroshima City Hospital
🇯🇵Hiroshima, Japan
National Disaster Medical Center
🇯🇵Tachikawa, Tokyo, Japan
Sakakibara Heart Institute of Okayama
🇯🇵Okayama, Japan
Nara Prefecture General Medical Center
🇯🇵Nara, Japan
Saitama Citizens Medical Center
🇯🇵Saitama, Japan
St. Luke's International Hospital
🇯🇵Tokyo, Japan
Tsuchiura Kyodo General Hospital
🇯🇵Tsuchiura, Ibaraki, Japan
Hirosaki University Hospital
🇯🇵Hirosaki, Aomori, Japan
National Cerebral and Cardiovascular Center Hospital
🇯🇵Suita, Osaka, Japan
Japanese Red Cross Fukuoka Hospital
🇯🇵Fukuoka, Japan
Osaka General Medical Center
🇯🇵Osaka, Japan
Juntendo University Nerima Hospital
🇯🇵Tokyo, Japan
Tokyo Metropolitan Bokutoh Hospital
🇯🇵Tokyo, Japan
Tokushima University Hospital
🇯🇵Tokushima, Japan
Nagoya University Hospital
🇯🇵Nagoya, Aichi, Japan
Hyogo Prefectural Awaji Medical Center
🇯🇵Sumoto, Awaji, Japan
Funabashi Municipal Medical Center
🇯🇵Funabashi, Chiba, Japan
Fukuokaken Saiseikai Futsukaichi Hospital
🇯🇵Chikushino, Fukuoka, Japan
Kameda Medical Center
🇯🇵Kamogawa, Chiba, Japan
Ogaki Municipal Hospital
🇯🇵Ogaki, Gifu, Japan
Kurume University Hospital
🇯🇵Kurume, Fukuoka, Japan
Medical Corporation Sapporo Heart Center
🇯🇵Sapporo, Hokkaido, Japan
Sapporo Higashi Tokushukai Hospital
🇯🇵Sapporo, Hokkaido, Japan
Iwate Prefectural Cyuou Hospital
🇯🇵Morioka, Iwate, Japan
Gunma University Hospital
🇯🇵Maebashi, Gunma, Japan
Tokai University Hospital
🇯🇵Isehara, Kanagawa, Japan
Kochi Medical School Hospital
🇯🇵Nankoku, Kochi, Japan
Nara Medical University Hospital
🇯🇵Kashihara, Nara, Japan
Urasoe General Hospital
🇯🇵Urasoe, Okinawa, Japan
Kindai University Hospital
🇯🇵Osakasayama, Osaka, Japan
Kasukabe Chuo General Hospital
🇯🇵Kasukabe, Saitama, Japan
Saitama Medical Center
🇯🇵Kawagoe, Saitama, Japan
Kawaguchi Cardiovascular and Respiratory Hospital
🇯🇵Kawaguchi, Saitama, Japan
Soka City Hospital
🇯🇵Soka, Saitama, Japan
Seirei Mikatahara General Hospital
🇯🇵Hamamatsu, Shizuoka, Japan
Juntendo University Shizuoka Hospital
🇯🇵Izunokuni, Shizuoka, Japan
Saiseikai Utsunomiya Hospital
🇯🇵Utsunomiya, Tochigi, Japan
Kitasato University Hospital
🇯🇵Kanagawa, Japan
Kitano Hospital
🇯🇵Osaka, Japan
Nakagami Hospital
🇯🇵Okinawa, Japan
Nihon University Itabashi Hospital
🇯🇵Tokyo, Japan
Juntendo University Hospital
🇯🇵Tokyo, Japan
Nippon Medical School Hospital
🇯🇵Tokyo, Japan
Tokyo Medical University
🇯🇵Tokyo, Japan
St.Marianna University School of Medicine Hospital
🇯🇵Kawasaki, Kanagawa, Japan
Shonan Kamakura General Hospital
🇯🇵Kamakura, Kanagawa, Japan
Kushiro-sanjikai Hospital
🇯🇵Kushiro, Hokkaido, Japan
Yokohama City University Medical Center
🇯🇵Yokohama, Japan