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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05392764
Other study ID # jRCTs031210682
Secondary ID
Status Recruiting
Phase Phase 3
First received
Last updated
Start date September 10, 2022
Est. completion date June 30, 2025

Study information

Verified date March 2024
Source Juntendo University
Contact Yuya Matsue, MD
Phone 81-3-3813-3111
Email yuya8950@gmail.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Recruiting
Enrollment 500
Est. completion date June 30, 2025
Est. primary completion date March 31, 2025
Accepts healthy volunteers No
Gender All
Age group 20 Years to 89 Years
Eligibility Inclusion Criteria: Patients who meet the below inclusion criteria will be randomized within 12 h after presentation to the hospital 1. Age of =20 and <90 years 2. 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. 3. 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. 4. Provided written consent to participate in the study Exclusion Criteria: 1. eGFR <20 mL/min/1.73m2 at the time of admission 2. Already taking an SGLT2i within 3 months prior to hospitalization 3. Type 1 diabetes mellitus 4. Systolic blood pressure <90 mmHg 5. Expected to newly require treatment with thiazide, tolvaptan, or carperitide within 48 h after hospitalization 6. 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) 7. Acute coronary syndrome, pulmonary thromboembolism, or a cerebrovascular accident is the main cause of the present hospitalization. 8. At risk of ketoacidosis or hyperosmolar hyperglycaemia 9. On dialysis, including peritoneal dialysis, or the initiation of dialysis during hospitalization is planned 10. Pregnant or lactating women 11. 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 12. A diagnosis of acute coronary syndrome, cerebral infarction, or transient ischemic attack made within 90 days 13. Ventricular tachycardia with syncope within 90 days 14. 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 15. Intubated at the time of screening or expected to require intubation within 48 h after hospitalization 16. 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) 17. 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. 18. A diagnosis of peripartum cardiomyopathy made within 6 months 19. Active myocarditis 20. Presence of uncontrolled thyroid disease 21. Acute cardiac structural abnormalities (e.g., acute mitral regurgitation due to ruptured chordae tendineae) 22. 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. 23. 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 24. Alcohol use disorder of at least mild severity according to the DSM-V 25. A diagnosis of active malignancy or suspected active malignancy made within 2 years 26. Coexisting diseases other than heart failure with an expected survival prognosis of =1 year 27. Participation in a clinical study of another drug 30 days before hospitalization 28. Patients considered to require fasting at screening. 29. Other conditions likely to interfere with the patient's safety or compliance with the protocol 30. Other patients who are considered unsuitable by the principal investigator or other investigators

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Empagliflozin 10 MG
once-daily oral empagliflozin 10 mg
Placebo
Placebo matching empagliflozin 10 mg

Locations

Country Name City State
Japan Nishiarai Hospital Adachi Tokyo
Japan Anjo Kosei Hospital Anjo Aichi
Japan Fukuokaken Saiseikai Futsukaichi Hospital Chikushino Fukuoka
Japan Mitsui Memorial Hospital Chiyoda Tokyo
Japan Sakakibara Heart Institute Fuchu Tokyo
Japan Japanese Red Cross Fukuoka Hospital Fukuoka
Japan Funabashi Municipal Medical Center Funabashi Chiba
Japan Tokyo Medical University Hachioji Medical Center Hachioji Tokyo
Japan Hyogo Brain and Heart Center Himeji Hyogo
Japan Hirosaki University Hospital Hirosaki Aomori
Japan Hiroshima City Hospital Hiroshima
Japan Tokai University Hospital Isehara Kanagawa
Japan Juntendo University Shizuoka Hospital Izunokuni Shizuoka
Japan Kameda Medical Center Kamogawa Chiba
Japan Nara Medical University Hospital Kashihara Nara
Japan Kasukabe Chuo General Hospital Kasukabe Saitama
Japan Saitama Medical Center Kawagoe Saitama
Japan Kawaguchi Cardiovascular and Respiratory Hospital Kawaguchi Saitama
Japan St.Marianna University School of Medicine Hospital Kawasaki Kanagawa
Japan Chikamori Hospital Kochi
Japan Kurume University Hospital Kurume Fukuoka
Japan Gunma University Hospital Maebashi Gunma
Japan International University of Health and Welfare Mita Hospital Minato Tokyo
Japan Toranomon Hospital Minato Tokyo
Japan Iwate Prefectural Cyuou Hospital Morioka Iwate
Japan Nagoya University Hospital Nagoya Aichi
Japan Kochi Medical School Hospital Nankoku Kochi
Japan Nara Prefecture General Medical Center Nara
Japan Sakakibara Heart Institute of Okayama Okayama
Japan Nakagami Hospital Okinawa
Japan Kitano Hospital Osaka
Japan Osaka General Medical Center Osaka
Japan Kindai University Hospital Osakasayama Osaka
Japan Saitama Citizens Medical Center Saitama
Japan Sapporo Higashi Tokushukai Hospital Sapporo Hokkaido
Japan Tokyo Women's Medical University Hospital Shinjuku Tokyo
Japan Soka City Hospital Soka Saitama
Japan National Cerebral and Cardiovascular Center Hospital Suita Osaka
Japan Hyogo Prefectural Awaji Medical Center Sumoto Awaji
Japan National Disaster Medical Center Tachikawa Tokyo
Japan Tokushima University Hospital Tokushima
Japan Juntendo University Hospital Tokyo
Japan Juntendo University Nerima Hospital Tokyo
Japan Nihon University Itabashi Hospital Tokyo
Japan Tokyo Medical University Tokyo
Japan Tokyo Metropolitan Bokutoh Hospital Tokyo
Japan Tsuchiura Kyodo General Hospital Tsuchiura Ibaraki
Japan Urasoe General Hospital Urasoe Okinawa
Japan Juntendo University Urayasu Hospital Urayasu Chiba
Japan Saiseikai Utsunomiya Hospital Utsunomiya Tochigi
Japan Yokohama City University Medical Center Yokohama

Sponsors (2)

Lead Sponsor Collaborator
Juntendo University Boehringer Ingelheim

Country where clinical trial is conducted

Japan, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 WHF, worsening heart failure Up to 90 days
Secondary A hierarchical composite endpoint consisting of death within 90 days, heart failure readmission within 90 days, and WHF during hospitalization WHF, worsening heart failure Up to 90 days
Secondary 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 WHF, worsening heart failure Up to 90 days
Secondary Change in NT-proBNP from randomization to 48 hours Evaluated at 48 hours after randomization
Secondary 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
Secondary Improvement in KCCQ-TSS of =5 points from randomization to 30 and 90 days after treatment initiation KCCQ-TSS, Kansas City Cardiomyopathy Questionnaire - Total Symptom Score. The scores range from 0 to 100, with 100 being the best possible score. Up to 90 days
Secondary Time to hemodynamic stabilization during index hospitalization During index hospitalization
Secondary Re-worsening of heart failure during index hospitalization During index hospitalization
Secondary Heart failure rehospitalization Up to 90 days
Secondary Death Up to 90 days
Secondary Urine output during the 48 h after randomization Evaluated at 48 hours after randomization
Secondary Cardiovascular death Up to 90 days
Secondary Change in the visual analog scale score for dyspnea from after randomization to 24 and 48 h The scores range from 0 to 100, with 100 being the best possible score. Evaluated at 24 and 48 hours after randomization
Secondary Change in high sensitivity cardiac troponin T Evaluated at 48 hours after randomization
Secondary Change in the KCCQ-TSS after randomization to 30 and 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. Up to 90 days
Secondary 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
Secondary Trend in eGFR after randomization to 24 h, 48 h, 30 days, and 90 days Up to 90 days
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