BIOmarker Based Diagnostic TOOLkit to Personalise Pharmacological Approaches in Congestive Heart Failure: the BIOTOOL-CHF Validation Trial

Overview

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

• Other Intervention: 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 physician

Primary outcome measures

• Win Ratio of Participants in Hierarchical Composite Endpoint (All-Cause Death, Heart Failure Events, and KCCQ-TSS Change) at 3 Months [Time frame: 3 months]

Secondary outcome measures (10)

• Time to All-Cause Death [Time frame: 3 months]
• Number of Heart Failure Events per Participant [Time frame: 3 months]
• Change from Baseline in Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS) [Time frame: Baseline and 3 months]
• Percent Change from Baseline in Bio-Adrenomedullin (Bio-ADM) Plasma Concentration [Time frame: Baseline and 3 months]
• Percent Change from Baseline in Serum CA-125 [Time frame: Baseline and 3 months]
• Percent Change from Baseline in Serum NT-proBNP [Time frame: Baseline and 3 months]
• Number of Participants with Dyskalemia [Time frame: 3 months]
• Number of Participants Receiving at Least 50% of Target GDMT Doses [Time frame: 3 months]
• Number of Participants Receiving All Recommended GDMT Classes [Time frame: 3 months]
• Number of Participants with Ventricular Arrhythmia Leading to Implantable Cardioverter-Defibrillator (ICD) Intervention [Time frame: 3 months]

Eligibility criteria

Inclusion criteria

• Adult patients with symptomatic chronic heart failure diagnosed at least 3 months prior to randomization
• Treatment with at least 40 mg of oral furosemide or equivalent at the time of enrolment to control symptoms
• 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

• Acute coronary syndrome or cerebrovascular accident in the previous 30 days
• Acute heart failure requiring immediate hospitalization or intravenous therapy (acute pulmonary edema, cardiogenic shock, arrhythmic storm)
• Clinical congestion score greater or equal to 5 at the time of randomization
• 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
• Active myocarditis
• Patients with any wearable or implantable device for congestion monitoring which is actively used to guide clinical practice
• Patients with left ventricular assist device (LVAD)/ biventricular assist device (Bi-VAD) or heart transplantation
• Severe stenotic valvular disease
• Glomerular Filtration Rate (GFR) <15 ml/min (estimated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)) or dialysis (hemodialysis or peritoneal dialysis)
• Liver cirrhosis with ascites
• Significant cognitive impairment
• Pregnancy or planned pregnancy during the study period
• Active malignancy or severe hematological disorders

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Supportive care

Study locations

Italy · 1 center

• IRCCS Azienda Ospedaliero-Universitaria di Bologna — Bologna

Identifiers

NCT: NCT07635810 · BIOTOOL-CHF VALID · 101095653

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗