Effects of Continued Administration of Empagliflozin in Patients With Heart Failure on Active SGLT2 Inhibitor Treatment Admitted for Acute Decompensated Heart Failure

Обзор

The goal of this clinical trial is to test the hypothesis that the continuation of empagliflozin during decongestive therapy in the setting of acute decompensated and hospitalized heart failure patients is not inferior compared to therapy cessation during the acute heart failure hospitalization. Randomized treatment (plus standard medical care) in patients with acute decompensated heart failure is one (1) tablet daily of empagliflozin 10 mg or matching placebo during the in-hospital stay (up to a maximum of 30 days), followed by treatment with empagliflozin 10 mg daily after discharge (but no later than day 31) until day 90. The primary outcome measure is the combined hierarchical endpoint of all-cause mortality, heart failure hospitalization and worsening renal function at 90 days after admission. Secondary outcome measures are the effects on urine output, diuretic efficiency, quality-of-life and the need for further administration of diuretics. Participants will * Take one tablet of study medication once daily (day 1 to day 90) * Restrict fluid intake to 1.5 liters of fluid per day and record the daily fluid intake for the study from day 1 to day 6 in the patient diary * Measure the urine output (day 1 to day 6) * Fill in Questionnaires (EQ-5D-3L (3-level version of the EuroQol five dimensional descriptive system), KCCQ-12 (Kansas City Cardiomyopathy Questionnaire comprising 12 items)) on day 0 (Baseline), at hospital discharge, and on day 30

Вмешательства

• Препарат Empagliflozin 10 MG Oral Tablet [Jardiance]
  Randomized treatment with 10 mg empagliflozin (Jardiance, one tablet) daily from day 1 until the day of hospital discharge, but no longer than 30 days, followed by 10 mg empagliflozin (Jardiance, one tablet) daily until day 90
• Препарат Placebo
  Randomized treatment with placebo (one tablet) daily from day 1 until the day of hospital discharge, but no longer than 30 days, followed by 10 mg empagliflozin (Jardiance, one tablet) daily until day 90

Первичные конечные точки

• Four-step hierarchical composite primary endpoint; win ratio based on the following parameters (day 90): time to all-cause death, number of heart failure events per patient, time to first heart failure event, eGFR decrease from baseline to day 90 [Срок оценки: day 90]

Вторичные конечные точки (12)

• Cardiovascular and total mortality on day 90 [Срок оценки: day 90]
• Number of patients alive and without re-hospitalization on day 90 [Срок оценки: day 90]
• Re-hospitalization after initial discharge, including reason: time to first rehospitalization after discharge [Срок оценки: day 90]
• Re-hospitalization after initial discharge, including reason: numbers of re-hospitalizations [Срок оценки: day 90]
• Number of patients with a decrease in eGFR of 5 ml/min/1.73 m² or more from baseline to day 90 [Срок оценки: day 90]
• Daily and cumulative urine output (UOP, ml) measured from day 1 until day 6 [Срок оценки: day 1 until day 6]
• Diuretic efficiency (ml urine per mg furosemide equivalent) from day 1 to day 6 [Срок оценки: day 1 until day 6]
• Change in body weight from baseline to day 1, day 3, day 6, discharge (supposed between day 6-10), day 30, and day 90 [Срок оценки: day 1, day 3, day 6, discharge (supposed between day 6-10), day 30, and day 90]
• Renal function at baseline, day 3, day 6, day 30, and day 90 [Срок оценки: baseline, day 3, day 6, day 30, and day 90]
• Liver function: bilirubin (nmol/ml) at baseline, day 3, day 6, day 30, and day 90 [Срок оценки: baseline, day 3, day 6, day 30, and day 90]
• Liver function: serum aminotransferases (µmol/l*s) at baseline, day 3, day 6, day 30, and day 90 [Срок оценки: baseline, day 3, day 6, day 30, and day 90]
• Liver function: relevant change in coagulation status (Quick/INR, %, 3X upper limit of normal) at baseline, day 3, day 6, day 30, and day 90 [Срок оценки: baseline, day 3, day 6, day 30, and day 90]

Критерии участия

Критерии включения

• Patients (age ≥ 18 years) with acute decompensated heart failure (HF) according to clinical assessment on active therapy with a SGLT2 inhibitor
• Brain Natriuretic Peptide (BNP) >100 pg/ml or N-terminal pro-BNP (NTproBNP) >300 pg/ml
• Written informed consent obtained
• Women of childbearing potential: negative pregnancy test and use of a highly effective method of contraception

Критерии исключения

• Type 1 diabetes mellitus
• Chronic Kidney Disease (CKD) with eGFR<20 ml/min, or end-stage renal failure with the need for chronic dialysis treatment
• Acute kidney injury (AKI) requiring dialysis treatment
• Known intolerance to empagliflozin
• Acute heart failure without signs of congestion ("dry" patient)
• Indication for coronary angiography or any foreseeable administration of a contrast media
• Need for hemofiltration or any other form of extracorporeal therapy
• Planned surgery
• Previous participation in this trial or recent participation in another clinical trial (within the last 4 weeks before inclusion)
• Identification of any causes of heart failure leading to decompensation that needs urgent management (like acute coronary syndrome, severe unstable arrhythmias, mechanical causes, acute pulmonary embolism)
• Incapacity to understand and / or to provide written informed consent
• Obvious uncontrolled substance abuse
• Pregnancy, breastfeeding

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Германия · 9 центров

• Jena University Hospital — Jena
• Kerckhoff-Klinik GmbH — Bad Nauheim
• Herzzentrum Dresden GmbH Universitaetsklinik — Dresden
• Universitaetsmedizin Goettingen — Göttingen
• Universitaetsklinikum Leipzig AöR — Leipzig
• Herzzentrum Leipzig GmbH — Leipzig
• Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR — Mainz
• LMU Klinikum Muenchen AöR — München
• … и ещё 1 центр

Идентификаторы

NCT: NCT07038356 · EMPA-CON_ZKSJ0162 · 2024-517977-26-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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