Cardiac Amyloidosis
Conditions
Interventions
Placebo control group:Administer placebo of vericiguat (starting at 5 mg/day and titrating to 10 mg/day or the maximum tolerated dose).
Sponsors
Fuwai Hospital, Chinese Academy of Medical Sciences
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1) Immunoglobulin light chain cardiac amyloidosis patients aged 18-75 years, the diagnosis of cardiac amyloidosis should meet the following criteria: abnormal serum free light chain quantification or ratio or abnormal blood/urine immunofixation electrophoresis; Amyloidosis was confirmed by abdominal fat, bone marrow and other tissues biopsy. There was imaging evidence of cardiac involvement (interventricular septal thickness > 12mm, excluding other heart diseases). Or light chain cardiac amyloidosis confirmed by endomyocardial biopsy; 2) Patients with immunoglobulin light chain cardiac amyloidosis who achieved at least partial response (PR) after at least 4 cycles of anti-plasma cell therapy; 3) Stable heart failure (NYHA class II-IV) lasting more than 4 weeks; 4) NT-proBNP>=450pg/mL (without AF); NT-proBNP>=600pg/mL (with atrial fibrillation); 5) Systolic blood pressure >90mmHg before randomization. Note: Partial response (PR) was defined as: Patients with dFLC>50 mg/L: dFLC decreased >50%; Patients with dFLC between 20 and 50 mg/L: dFLC<10 mg/L
Exclusion criteria
Exclusion criteria: Patients who meet any of the following criteria will be excluded: 1) Hemodynamically unstable acute decompensated heart failure, or mechanical hemodynamic support/invasive mechanical ventilation within 14 days prior to randomization; intravenous inotropic agents, vasoactive drugs, or intravenous diuretics within 7 days prior to randomization. 2) Poorly controlled hypertension, defined as resting systolic blood pressure >=180 mmHg and/or diastolic blood pressure >=110 mmHg on two separate measurements prior to randomization. 3) Six-minute walk distance >450 meters or KCCQ-CSS score >90 points during the screening period. 4) Myocardial infarction, unstable angina, percutaneous coronary intervention (PCI), or cardiac surgery within 3 months prior to screening; or cardiac resynchronization therapy (CRT) device implantation within 6 months prior to screening. 5) Transthyretin-type cardiac amyloidosis. 6) History of syncope, stroke, or transient ischemic attack (TIA) within 6 months prior to screening; major surgery within 6 months prior to screening. 7) Comorbid active myocarditis, uncorrected severe arrhythmia, constrictive pericarditis, or clinically significant congenital heart disease. 8) Severe primary diseases of the liver, kidneys, hematopoietic system, nervous system, endocrine system, etc.; cancer patients; or psychiatric disorders. 9) Non-heart failure-related transaminase or bilirubin levels exceeding 3 times the upper limit of normal at screening; renal disease or eGFR <15 mL/min/1.73m^2, or history of dialysis. 10) Uncorrected thyroid disorders, infections, autoimmune diseases, severe anemia, pulmonary embolism, exacerbation of chronic obstructive pulmonary disease, or any type of severe pulmonary hypertension. 11) The investigator deems that the patient may require the following treatments within 3 months after randomization: planned revascularization, implantable cardioverter-defibrillator (ICD), or cardiac resynchronization therapy (CRT) implantation. 12) Severe valvular stenosis/regurgitation requiring interventional or surgical treatment within 6 months. 13) History of heart transplantation, or planned ventricular assist device/heart transplant surgery within 6 months. 14) Life expectancy less than 12 months. 15) History of allergy to any component of the study drug. 16) Severe comorbidities, social or economic issues, or history of noncompliance with medical regimens that may affect the patient’s ability to understand and/or adhere to the protocol or follow-up procedures, thereby preventing compliance with all study requirements. 17) Participation in another chronic heart failure trial or investigational drug/device study within 30 days prior to screening (defined as less than 30 days from screening) or current participation in such a study. 18) Pregnant or breastfeeding women. 19) Inability to provide written informed consent.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in 6-minute walk distance from baseline at week 24 after the first dose administration.;Change in NT-proBNP from baseline at week 24 after the first dose administration; | — |
Secondary
| Measure | Time frame |
|---|---|
| Composite endpoint of cardiovascular death and heart failure worsening rehospitalization at week 24 after the first dose administration;Cardiovascular death, all-cause death, and heart failure worsening rehospitalization at week 24 after the first dose administration;Change in KCCQ-CSS and KCCQ-OSS scores from baseline at week 24 after the first dose administration;Proportion of subjects with an increase in KCCQ-CSS and KCCQ-OSS scores of >=5, >=10, and >=15 points from baseline at week 24 after the first dose administration;Change in Peak VO? from baseline in cardiopulmonary exercise testing at week 24 after the first dose administration; | — |
Countries
China
Contacts
Public ContactYuhui Zhang
Fuwai Hospital, Chinese Academy of Medical Sciences
Outcome results
None listed