Patients with heart failure who are admitted or hospitalized due to worsening of heart failure desp heart failure
Conditions
Interventions
M201-A hydrochloride injection once or twice a day for heart failure patients who are hospitalized or hospitalized due to exacerbation of heart failure despite the use of existing oral heart failure t
Sponsors
Shimamoto Ken
Aetas Pharma Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects who meet all of the following criteria will be eligible for this clinical trial. (1) Japanese adult, male or female (2) Persons who are hospitalized or currently hospitalized due to worsening of heart failure* despite using oral heart failure medications (including oral diuretics) *: Exacerbation of heart failure is a condition in which one or more of the following is observed: dyspnea, pulmonary congestion, pulmonary rales, onset or progression of edema, and short-term weight gain. (3) Persons who are 20 years or older and less than 86 years old on Day -2 before the start of the study drug administration (4) Persons with heart failure determined to be grade II or III according to NYHA classification (HFrEF, HFmrEF, or HFpEF) (5) Persons with eGFR less than 60 mL/min/1.73 m2 and more than 30 mL/min/1.73 m2 (6) Those whose weight is 40 kg or more for women and 45 kg or more for men, and whose BMI* is 18.0 or more and less than 30.0. *: BMI = Weight (kg) / [Height (m)2] (rounded down to the second decimal place) (7) Subjects who are able to measure urine storage and water intake, and measure body weight after urinating every morning before administering the study drug. (8) Subjects who have given written consent to participate in this clinical trial based on their own free will.
Exclusion criteria
Exclusion criteria: In this clinical trial, subjects who fall under any of the following exclusion criteria will not be included in this clinical trial, considering the impact on subject safety and efficacy. (1) Persons hospitalized for acute myocardial infarction and less than 30 days after onset of symptoms (2) Persons with cardiogenic shock (3) Subjects who received emergency infusion treatment with catecholamines, carperitide (hANP), tolvaptan sodium phosphate (Samutas), or vasodilators, which are injectable treatments for heart failure, within 30 days before the start of study drug administration. (4) Loop diuresis must be completed within 32 hours before the scheduled morning administration time on Day 1 (if administration starts at 9 a.m. on Day 1, from 1 a.m. on Day -1 until before the start of study drug administration on Day 1). Those who received a bolus dose of drug injections If a bolus of the above loop diuretic injection is administered on Day -1, Day -1 shall be reset and the necessary tests shall be conducted. For handling when using loop diuretic injections, see "7.9 Emergency Measures/Treatment." (5) Subjects who used antiarrhythmic drugs for the period specified below before starting study drug administration. Amiodarone: within 1 year Group IV (bepridil): within 14 days Group Ia, Group Ic, Group III: within 7 days For details on drugs applicable to Group Ia, Group Ic, and Group III, see Table 7.8-1 in "7.8.1 Drugs prohibited for concomitant use." (6) Those whose creatinine value exceeds 2.5 mg/dL (7) Subjects who have newly administered, changed the dose, or discontinued an SGLT2 inhibitor within 120 days before starting study drug administration. (8) Subjects with QTcF of 440 ms or more in standard 12-lead electrocardiogram measurement. However, this standard does not apply to patients with atrial fibrillation. (9) Persons with risk factors for torsade de pointes (TdP) (e.g., hypokalemia, hypomagnesemia, history or complications of unexplained syncope, long QT syndrome or a family history thereof) etc) (10) Persons with BNP less than 100 pg/mL or NT-proBNP less than 400 pg/mL (11) Tests from 6 months before administration of the study drug to Day -1 and whose serum potassium level has ever been less than 3.6 mEq/L or more than 5.5 mEq/L (12) Subjects whose serum magnesium level has been found to be 1.8 mg/dL or less at least once during a test between 6 months before administration of the study drug and Day -1. (13) Persons with blood hemoglobin levels less than 9 g/dL (14) Persons with bradycardia with heart rate below 50 or sinus arrest for 2 seconds or more (15) Persons with grade II Mobitz type atrioventricular block or grade III atrioventricular block (16) Persons with systolic blood pressure less than 90 mmHg (17) Persons with sustained ventricular tachycardia (18) Persons who have a cardiac assist circulation device or a biventricular pacemaker implanted. (19) Those who have undergone cardiac surgery within 60 days before administration of the study drug (20) Persons undergoing endotracheal intubation (21) Persons undergoing artificial dialysis (22) Persons with treatment-resistant, refractory, or end-stage heart failure who are considered for special treatment including ventricular assist device or heart transplantation. (23) Persons with severe aortic valve stenosis, severe left ventricular hypertrophy, serious gastrointestinal (gastrointestinal, liver, gallbladder, bile duct, pancreas, etc.) diseases, severe thyroid dysfunct
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety evaluation items Adverse events and side effects Vital signs (body temperature, blood pressure/pulse rate) Laboratory test values (general blood/biochemical tests, blood renal function tests, urinalysis (qualitative/biochemistry), urinalysis (kidney function) Standard 12-lead ECG and Holter ECG Effectiveness evaluation items Urine volume Urinary Na, Cl, K excretion Water balance (difference between the amount of water consumed, amount of water in meals, amount of transfusion, etc., and urine amount) Change in weight NYHA classification Evaluate pulmonary congestion with chest X-ray Assessment of congestion (edema, pulmonary crackles) Renal function indicators (serum Cre, serum BUN, serum Cystatine C, eGFRcystatine, eGFRcre, CCr, urinary NAG, urinary beta2 microglobulin, urinary L-FABP, urinary albumin, etc.) Change in blood BNP Inferior vena cava diameter (during inspiration and expiration) Cardiac function measured by cardiac ultrasound: cardiac chamber inner diameter size, ventricular wall motion, left ventricular shortening (FS), left ventricular ejection fraction (EF), tricuspid regurgitation pressure gradient, left ventricular inflow Fast waveform (early diastolic wave/atrial systolic wave: E/A), E wave deceleration time (DT), left ventricular early diastolic wave/mitral valve annulus movement speed E/E', Presence of pericardial effusion, aortic diameter (AoD), left atrial diameter (LAD), left ventricular end-diastolic diameter (LVDd), left ventricular end-systolic diameter (LVDs), left ventricular wall thickness [ventricular septal thickness (IVSth)], posterior wall thickness (PWth)], left ventricular outflow tract waveform (LVOF VTI), left atrial volume index (LAVI) Percentage of subjects who received additional/emergency drug therapy for heart failure between Day 1 and Day 8 and discontinued it Percentage of subjects who received a bolus of loop diuretic injection between Day 1 and Day 8 The period from the start of the study drug administration (Day | — |
Contacts
Public ContactYuji Kumagai
The Kitasato Institute
Outcome results
None listed