Early Treatment With a Sodium-glucose Co-transporter 2 Inhibitor in High-risk Patients With Acute Heart Failure

NCT05392764 | Recruiting Phase 3 DMC

• 1 other identifier: jRCTs031210682
• Study Type: interventional
• Target: 444
• Locations: 1 country
• Sites: 69

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.

Conditions

Acute Heart Failure

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (17)

• A hierarchical composite endpoint consisting of death within 90 days, heart failure readmission within 90 days, and WHF during hospitalization

  Up to 90 days

• 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

• 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

• Improvement in KCCQ-TSS of ≥5 points from randomization to 30 and 90 days after treatment initiation

  Up to 90 days

Study Arms (2)

Empagliflozin

EXPERIMENTAL

Patients will be randomized 1:1 to either empagliflozin or placebo.

Drug: Empagliflozin 10 MG

Placebo

PLACEBO COMPARATOR

Placebo matching empagliflozin

Drug: Placebo

Interventions

Empagliflozin 10 MG DRUG

once-daily oral empagliflozin 10 mg

Empagliflozin

Placebo DRUG

Placebo matching empagliflozin 10 mg

Placebo

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age of ≥20\*
• 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.
• 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.
• Provided written consent to participate in the study \*If the patient is 90 years of age or older and cognitive decline is considered necessary, Mini-Cog should be used to confirm that its score is not less than 3.

You may not qualify if:

• 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

Sponsors & Collaborators

• Juntendo University: lead
• Boehringer Ingelheim: collaborator

Study Sites (69)

Anjo Kosei Hospital

Anjo, Aichi-ken, Japan

RECRUITING

Aichi Medical University Hospital

Nagakute, Aichi-ken, Japan

RECRUITING

Nagoya University Hospital

Nagoya, Aichi-ken, Japan

RECRUITING

Hirosaki University Hospital

Hirosaki, Aomori, Japan

RECRUITING

Hyogo Prefectural Awaji Medical Center

Sumoto, Awaji, Japan

ACTIVE NOT RECRUITING

Funabashi Municipal Medical Center

Funabashi, Chiba, Japan

RECRUITING

Kameda Medical Center

Kamogawa, Chiba, Japan

RECRUITING

Juntendo University Urayasu Hospital

Urayasu, Chiba, Japan

RECRUITING

Fukuokaken Saiseikai Futsukaichi Hospital

Chikushino-shi, Fukuoka, Japan

RECRUITING

Japanese Red Cross Fukuoka Hospital

Fukuoka, Fukuoka, Japan

RECRUITING

Kurume University Hospital

Kurume, Fukuoka, Japan

RECRUITING

Ogaki Municipal Hospital

Ōgaki, Gifu, Japan

RECRUITING

Gunma University Hospital

Maebashi, Gunma, Japan

RECRUITING

Hiroshima City Hospital

Hiroshima, Hiroshima, Japan

RECRUITING

Kushiro-sanjikai Hospital

Kushiro, Hokkaido, Japan

RECRUITING

Medical Corporation Sapporo Heart Center

Sapporo, Hokkaido, Japan

RECRUITING

Sapporo Higashi Tokushukai Hospital

Sapporo, Hokkaido, Japan

RECRUITING

Tsuchiura Kyodo General Hospital

Tsuchiura, Ibaraki, Japan

RECRUITING

Iwate Prefectural Cyuou Hospital

Morioka, Iwate, Japan

RECRUITING

Tokai University Hospital

Isehara, Kanagawa, Japan

RECRUITING

Shonan Kamakura General Hospital

Kamakura, Kanagawa, Japan

RECRUITING

St.Marianna University School of Medicine Hospital

Kawasaki, Kanagawa, Japan

RECRUITING

Chikamori Hospital

Kochi, Kochi, Japan

RECRUITING

Kochi Medical School Hospital

Nankoku, Kochi, Japan

RECRUITING

Nara Medical University Hospital

Kashihara, Nara, Japan

RECRUITING

Nara Prefecture General Medical Center

Nara, Nara, Japan

RECRUITING

Sakakibara Heart Institute of Okayama

Okayama, Okayama-ken, Japan

RECRUITING

Nakagami Hospital

Okinawa, Okinawa, Japan

ACTIVE NOT RECRUITING

Urasoe General Hospital

Urasoe, Okinawa, Japan

RECRUITING

Kitano Hospital

Osaka, Osaka, Japan

RECRUITING

Osaka General Medical Center

Osaka, Osaka, Japan

RECRUITING

Kindai University Hospital

Sayama, Osaka, Japan

RECRUITING

National Cerebral and Cardiovascular Center Hospital

Suita, Osaka, Japan

RECRUITING

Kasukabe Chuo General Hospital

Kasukabe, Saitama, Japan

RECRUITING

Saitama Medical Center

Kawagoe, Saitama, Japan

RECRUITING

Kawaguchi Cardiovascular and Respiratory Hospital

Kawaguchi, Saitama, Japan

RECRUITING

Saitama Citizens Medical Center

Saitama, Saitama, Japan

ACTIVE NOT RECRUITING

Soka City Hospital

Sōka, Saitama, Japan

RECRUITING

Seirei Mikatahara General Hospital

Hamamatsu, Shizuoka, Japan

RECRUITING

Juntendo University Shizuoka Hospital

Izunokuni, Shizuoka, Japan

RECRUITING

Saiseikai Utsunomiya Hospital

Utsunomiya, Tochigi, Japan

RECRUITING

Tokushima University Hospital

Tokushima, Tokushima, Japan

RECRUITING

Nishiarai Hospital

Adachi City, Tokyo, Japan

ACTIVE NOT RECRUITING

Mitsui Memorial Hospital

Chiyoda City, Tokyo, Japan

RECRUITING

Sakakibara Heart Institute

Fuchū, Tokyo, Japan

RECRUITING

Tokyo Medical University Hachioji Medical Center

Hachiōji, Tokyo, Japan

RECRUITING

International University of Health and Welfare Mita Hospital

Minato, Tokyo, Japan

RECRUITING

Toranomon Hospital

Minato, Tokyo, Japan

RECRUITING

Tokyo Women's Medical University Hospital

Shinjuku, Tokyo, Japan

RECRUITING

National Disaster Medical Center

Tachikawa, Tokyo, Japan

RECRUITING

Juntendo University Nerima Hospital

Tokyo, Tokyo, Japan

RECRUITING

Tokyo Metropolitan Bokutoh Hospital

Tokyo, Tokyo, Japan

ACTIVE NOT RECRUITING

Yokohama City University Medical Center

Yokohama, Yokohama, Japan

RECRUITING

Iizuka Hospital

Fukuoka, Japan

RECRUITING

Gifu University Graduate school of Medicine

Gifu, Japan

RECRUITING

Nayoro City General Hospital Contact:

Hokkaido, Japan

RECRUITING

International Goodwill Hospital

Kanagawa, Japan

RECRUITING

Kitasato University Hospital

Kanagawa, Japan

RECRUITING

SHOWA Medical University Fujigaoka Hospital

Kanagawa, Japan

RECRUITING

Hanwa Memorial Hospital

Osaka, Japan

RECRUITING

Osaka Medical and Pharmaceutical University Hospital

Osaka, Japan

RECRUITING

Juntendo University Hospital

Tokyo, Japan

RECRUITING

Nihon University Itabashi Hospital

Tokyo, Japan

RECRUITING

Nippon Medical School Hospital

Tokyo, Japan

RECRUITING

St. Luke's International Hospital

Tokyo, Japan

RECRUITING

The Jikei University Hospital

Tokyo, Japan

RECRUITING

Tokyo General Hospital

Tokyo, Japan

RECRUITING

Tokyo Medical University

Tokyo, Japan

RECRUITING

Tokyo Saiseikai Central Hospital

Tokyo, Japan

RECRUITING

MeSH Terms

Interventions

empagliflozin

Study Officials

• Yuya Matsue, MD

  Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yuya Matsue, MD

CONTACT

81-3-3813-3111; yuya8950@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: May 14, 2022
• First Posted: May 26, 2022
• Study Start: September 10, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: February 13, 2026

Record last verified: 2026-02

Locations

JP (69)