Phase II Clinical Study of HRS-9057 Injection in Patients With Heart Failure-induced Fluid Retention

Официальное название

A Multicentre, Randomised, Double-blind, Placebo-controlled Phase II Clinical Study Evaluating the Efficacy and Safety of Injectable HRS-9057 in Patients With Heart Failure-induced Fluid Retention

Обзор

Phase II clinical study of HRS-9057 injection in patients with heart failure-induced fluid retention

Вмешательства

• Препарат HRS-9057 injection set
  HRS-9057 injection set
• Препарат 5% Glucose Injection or 0.9% sodium chloride injection
  5% Glucose Injection or 0.9% sodium chloride injection

Первичные конечные точки

• Absolute change in weight from baseline on day 8 [Срок оценки: within 8 days after the start of administration]

Вторичные конечные точки (7)

• Absolute change in body weight from baseline at each visit during treatment [Срок оценки: At each visit during treatment，within 8 days after the start of administration]
• The proportion of participants requiring remedial treatment during therapy as defined by the protocol [Срок оценки: after the last case has left the group，within 1years after the first case in]
• Total dose of loop diuretics during treatment [Срок оценки: within 8 days after the start of administration]
• The incidence and severity of any adverse events (AEs), adverse events of special interest (AESIs), and serious adverse events (SAEs) occurring after any treatment [Срок оценки: within 8 days after the start of administration]
• Incidence of hypernatraemia during treatment [Срок оценки: within 8 days after the start of administration]
• Proportion of participants who experienced hypovolaemic events during treatment and needed to discontinue the trial medication [Срок оценки: within 8 days after the start of administration]
• Detection indicators: concentrations of HRS-9057, tolvaptan and other major metabolites (if applicable) [Срок оценки: within 8 days after the start of administration]

Критерии участия

Критерии включения

• Aged ≥18 years on the day of signing the informed consent, regardless of gender;
• Hospitalization due to heart failure within 72 hours prior to randomization.;
• At screening and prior to randomization, presence of heart failure symptoms (exertional dyspnea, paroxysmal nocturnal dyspnea, orthopnea, etc.) and at least one sign of fluid retention, including: auscultatory rales in the lungs, pitting edema of the lower extremities, pulmonary congestion confirmed by chest imaging;;
• NT-proBNP > 450 pg/mL within 12 hours prior to randomization, or > 600 pg/mL in patients with atrial fibrillation; or BNP > 150 pg/mL, or > 200 pg/mL in patients with atrial fibrillation.
• Judged to have poor response to loop diuretics before randomisation: presence of symptoms and signs of fluid retention after the administration of a cumulative dose of oral or intravenous loop diuretics equivalent to oral furosemide ≥40 mg (or equivalent doses of other loop diuretics#) within the past 12 hours.

Критерии исключения

• Occurrence of myocardial infarction, stroke or transient ischemic attack, sustained ventricular tachycardia or ventricular fibrillation within 1 month prior to screening; or severe trauma or major/moderate surgery within 1 month prior to screening;
• Coronary revascularization (percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG)), valve repair/replacement, carotid or peripheral arterial revascularization, mechanical circulatory support device therapy, heart transplantation within 1 month prior to screening or planned during the study; or presence of severe coronary artery disease or cerebrovascular disease without revascularization that may lead to acute events during hospitalization;
• The signs and symptoms of fluid retention are judged by the investigator as mainly attributable to non-cardiac causes, including acute exacerbation of chronic obstructive pulmonary disease, severe anemia, decompensated cirrhosis, nephrotic syndrome, and so on.
• The investigator determines that this hospitalization is due to acute heart failure requiring initial correction of the underlying cause, including: coronary atherosclerotic heart disease requiring revascularization, active myocarditis, constrictive pericarditis, cardiac tamponade, complex congenital heart disease, or symptomatic severe untreated primary valvular heart disease that may lead to acute events during hospitalization;
• Previously diagnosed with hypertrophic cardiomyopathy and currently still in the hypertrophic phase (obstructive or non-obstructive), or amyloid cardiomyopathy;
• Use of cardiac mechanical assist device at the time of screening;
• Presence of hypovolemia or peripheral hypoperfusion at screening, assessed by the investigator as requiring treatment with vasoconstrictors, positive inotropic agents, or volume resuscitation.
• Anuria at the time of screening; or urinary difficulties caused by urinary tract obstruction, stones or tumours;
• Unable to perceive thirst at the time of screening, or any reason causing difficulty in fluid intake;
• Unable to complete weight measurement or urine collection;
• Consciousness impairment at the time of screening, or hepatic encephalopathy at the time of screening or a history of hepatic encephalopathy;
• Any organ system malignancy within the last 5 years requiring ongoing treatment such as chemotherapy, radiotherapy, endocrine therapy, targeted therapy, etc.;
• History of drug abuse or substance use within 1 year prior to screening.
• Individuals with a body mass index (BMI) below 18.5 kg/m² ;
• Symptomatic hypotension and/or systolic blood pressure <90 mmHg; 16. Estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m2 (calculated using the Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI2009\] formula based on serum creatinine), or undergoing/planned for haemodialysis or ultrafiltration therapy;

17\. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥3× the upper limit of normal (ULN), except if assessed by the investigator as due to heart failure; 18. Serum sodium > ULN or <125 mmol/L; 19. Serum potassium > ULN 20. Known or suspected allergy to tolvaptan tablets, OPC-61815 injection, or HRS-9057 injection components; 21. Participation in any drug or medical device clinical trial within 3 months prior to screening, defined as: signing the informed consent and using the investigational product (excluding placebo) or investigational medical device; or still within 5 half-lives of the investigational drug (whichever is longer); 22. Individuals who currently require blood transfusion therapy. 23. Participants with mental incapacity or speech disorders, or unable to fully understand or participate in the trial process, or unable to fully understand potential adverse reactions during the study; 24. Pregnant or breastfeeding women, or participants of childbearing potential unwilling to use protocol-specified contraception during the trial and for 1 week after the last dose; 25. As judged by the investigator, any condition affecting participant safety or otherwise interfering with the evaluation of trial results (medical, psychological, social, or geographical factors, etc.).

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

Китай · 1 центр

• Fuwai Hospital, Chinese Academy of Medical Sciences — Пекин

Идентификаторы

NCT: NCT07318103 · HRS-9057-201

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗