Congestive Heart Failure(CHF)
Conditions
Keywords
Congestion, Biomarkers, Heart failure
Brief summary
By the re-analysis, in the BIOTOOL-CHF DISCO study, of a previously enrolled cohort of patients, a Biological Congestion Score (BCS) was newly developed. The BCS integrates four congestion-related biomarkers with key clinical variables. The BIOTOOL-CHF VALID trial is designed to prospectively evaluate whether a BCS-assisted strategy for diuretic management improves clinical outcomes and quality of life in patients with chronic Heart Failure (HF) compared with standard care.
Detailed description
This prospective randomised study is part of a wider project that has been funded within the Horizon program by the call HORIZON-HLTH-2022-TOOL-11-01, project # 101095653, BIOTOOL-CHF. Herein the study will compare the outcomes of patients with chronic HF managed according to current usual clinical practice vs. patients in which therapy will be managed following the calculation of the BCS. In the BIOTOOL-CHF DISCO study, the BCS showed high accuracy in detecting congestion and better performance than clinical assessment in predicting outcomes, so it was hypothesized that, by providing a more accurate estimate of congestion in patients with chronic heart failure, the BCS may assist clinicians in managing diuretic therapy more accurately than the usual clinical assessment. The primary objective will be the comparison of standard-of-care management of chronic heart failure with a BCS-assisted strategy for guiding diuretic therapy, assessing the impact on a hierarchical composite clinical outcome at 3 months.
Interventions
OTHERIntervention: diuretic therapy guided by the Biological Congestion Score (BCS) using a predefined treatment nomogram
In patients randomized to the intervention arm, clinical variables and biomarker results will be entered into the score calculator. The calculator will provide to the clinician an estimate of the degree of congestion by the BCS, and the probability of cardiovascular hospitalization or death within the subsequent 3 months. Discrepancies will be recorded in the electronic Case Report Form (eCRF). Final decisions and eventual therapy adjustments will remain at the discretion of the caring physicians.
Sponsors
IRCCS Azienda Ospedaliero-Universitaria di Bologna
European Clinical Research Infrastructure Network
European Commission
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Adult patients with symptomatic chronic heart failure diagnosed at least 3 months prior to randomization 2. Treatment with at least 40 mg of oral furosemide or equivalent at the time of enrolment to control symptoms 3. At least one of the following: * At discharge from hospitalization for heart failure * History of hospitalization for heart failure in the previous 3 months * History of treatment with intravenous diuretics or inotropes in ambulatory setting in the previous 3 months * B-type Natriuretic Peptide (BNP) \> 400 pg/ml or N-terminal pro-B-type natriuretic peptide (NT-proBNP) \> 1000 pg/ml if in sinus rhythm or BNP \> 800 pg/ml or NT-proBNP \> 2000 pg/ml if in atrial fibrillation (AF) assessed within 4 weeks before enrolment
Exclusion criteria
1. Acute coronary syndrome or cerebrovascular accident in the previous 30 days 2. Acute heart failure requiring immediate hospitalization or intravenous therapy (acute pulmonary edema, cardiogenic shock, arrhythmic storm) 3. Clinical congestion score greater or equal to 5 at the time of randomization 4. Any cardiovascular intervention (cardiac surgery/coronary revascularization (Coronary Artery Bypass Grafting (CABG) or Percutaneous Coronary Intervention (PCI))/ Cardiac Resynchronization Therapy (CRT) implant, percutaneous treatment of valve disease, arrhythmias ablation) performed in the previous 3 months or planned in the following 3 months 5. Active myocarditis 6. Patients with any wearable or implantable device for congestion monitoring which is actively used to guide clinical practice 7. Patients with left ventricular assist device (LVAD)/ biventricular assist device (Bi-VAD) or heart transplantation 8. Severe stenotic valvular disease 9. Glomerular Filtration Rate (GFR) \<15 ml/min (estimated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)) or dialysis (hemodialysis or peritoneal dialysis) 10. Liver cirrhosis with ascites 11. Significant cognitive impairment 12. Pregnancy or planned pregnancy during the study period 13. Active malignancy or severe hematological disorders
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Win Ratio of Participants in Hierarchical Composite Endpoint (All-Cause Death, Heart Failure Events, and KCCQ-TSS Change) at 3 Months | 3 months | Title: Win Ratio of Hierarchical Composite Endpoint (All-Cause Death, Heart Failure Events, and Change in KCCQ-TSS) at 3 Months Description: To compare BCS-guided management vs. standard of care in chronic heart failure. The hierarchical composite endpoint is assessed using the win ratio method, combining in priority order: (1) time to all-cause death (days), (2) number of heart failure events (HF hospitalizations, emergency visits, or unplanned parenteral HF therapy; count), and (3) change from baseline in Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS; range 0-100 points, higher scores indicate better health status). The three components are combined into a single win ratio value via the hierarchical win ratio method; no separate unit applies to each component independently. Unit of Measure: Win Ratio |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change from Baseline in Serum CA-125 | Baseline and 3 months | Percent change from baseline to 3 months in serum CA-125, measured in U/mL. Unit of Measure: Percent change |
| Percent Change from Baseline in Serum NT-proBNP | Baseline and 3 months | Percent change from baseline to 3 months in serum N-terminal pro-B-type natriuretic peptide (NT-proBNP), measured in pg/mL. Unit of Measure: Percent change |
| Number of Participants with Dyskalemia | 3 months | Number of participants with at least one occurrence of dyskalemia, defined as serum potassium below 3.5 mEq/L or above 5.0 mEq/L at any time point. Unit of Measure: Number of Participants |
| Number of Participants Receiving at Least 50% of Target GDMT Doses | 3 months | Number of participants receiving at least 50% of the target dose for all prescribed Guideline-Directed Medical Therapy (GDMT) classes at 3 months. Unit of Measure: Number of Participants |
| Number of Participants Receiving All Recommended GDMT Classes | 3 months | Number of participants on all recommended Guideline-Directed Medical Therapy (GDMT) classes at 3 months: all 4 pillars for Heart Failure with Reduced Ejection Fraction (HFrEF) (Renin-Angiotensin-Aldosterone System (RAAS) inhibitor or Angiotensin Receptor-Neprilysin Inhibitor (ARNI), beta-blocker, Mineralocorticoid Receptor Antagonist (MRA), Sodium-Glucose Cotransporter-2 (SGLT2) inhibitor); SGLT2 inhibitor for Heart Failure with Mildly Reduced Ejection Fraction (HFmrEF)/Heart Failure with Preserved Ejection Fraction (HFpEF). Unit of Measure: Number of Participants |
| Number of Participants with Ventricular Arrhythmia Leading to Implantable Cardioverter-Defibrillator (ICD) Intervention | 3 months | Number of participants with ventricular arrhythmia leading to Implantable Cardioverter-Defibrillator (ICD) therapy, including anti-tachycardia pacing or shock, during the study period. Unit of Measure: Number of Participants |
| Number of Heart Failure Events per Participant | 3 months | Number of heart failure events per participant, including HF hospitalizations, emergency department visits for heart failure, and unplanned parenteral HF therapy. Unit of Measure: Number of events |
| Change from Baseline in Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS) | Baseline and 3 months | Change from baseline to 3 months in KCCQ-TSS. Scale range: 0 to 100 points; higher scores indicate better health status. Unit of Measure: Points |
| Percent Change from Baseline in Bio-Adrenomedullin (Bio-ADM) Plasma Concentration | Baseline and 3 months | Percent change from baseline to 3 months in plasma Bio-Adrenomedullin (bio-ADM), measured in pmol/L. Unit of Measure: Percent change |
| Time to All-Cause Death | 3 months | Time from randomization to death from any cause. Unit of Measure: Days |
Countries
Italy
Contacts
CONTACTLuciano Potena
Outcome results
None listed