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

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 HF compared with standard care.

Study Overview

• Status: Not yet recruiting
• Conditions: Congestive Heart Failure(CHF)
• Intervention / Treatment: Other: Intervention: diuretic therapy guided by the biological congestion score using a predefined treatment nomogram

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 with 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. Primary Objective will be the comparison 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.

• Study Type: Interventional
• Enrollment (Estimated): 600
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Luciano Potena; Phone Number: (+39) 0512143725; Email: luciano.potena2@unibo.it

Study Locations

• Italy
  • Bologna
    • Bologna, Bologna, Italy, 40138
      • IRCCS Azienda Ospedaliero-Universitaria di Bologna

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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:

   1. At discharge from hospitalization for heart failure
   2. History of hospitalization for heart failure in the previous 3 months
   3. History of treatment with intravenous diuretics or inotropes in ambulatory setting in the previous 3 months
   4. BNP> 400 pg/ml or 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 (CABG or PCI)/ 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) LVAD/ biventricular assist device (Bi-VAD) or heart transplantation;
8. Severe stenotic valvular disease;
9. GFR <15 ml/min (estimated by 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention Group	Other: Intervention: diuretic therapy guided by the biological congestion score 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 eCRF. Final decisions and eventual therapy adjustments will remain at the discretion of the caring physicians.
No Intervention: Control Group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Win Ratio of Participants in Hierarchical Composite Endpoint (All-Cause Death, Heart Failure Events, and KCCQ-TSS Change) at 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	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to All-Cause Death	Time from randomization to death from any cause. Unit of Measure: Days	3 months
Number of Heart Failure Events per Participant	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	3 months
Change from Baseline in Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS)	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	Baseline and 3 months
Percent Change from Baseline in Bio-Adrenomedullin (Bio-ADM) Plasma Concentration	Percent change from baseline to 3 months in plasma Bio-Adrenomedullin (bio-ADM), measured in pmol/L.Unit of Measure: Percent change	Baseline and 3 months
Percent Change from Baseline in Serum CA-125	Percent change from baseline to 3 months in serum CA-125, measured in U/mL. Unit of Measure: Percent change	Baseline and 3 months
Percent Change from Baseline in Serum NT-proBNP	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	Baseline and 3 months
Number of Participants with Dyskalemia	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	3 months
Number of Participants Receiving at Least 50% of Target GDMT Doses	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	3 months
Number of Participants Receiving All Recommended GDMT Classes	Number of participants on all recommended GDMT classes at 3 months: all 4 pillars for HFrEF (RAAS inhibitor or ARNI, beta-blocker, MRA, SGLT2 inhibitor); SGLT2 inhibitor for HFmrEF/HFpEF. Unit of Measure: Number of Participants	3 months
Number of Participants with Ventricular Arrhythmias Leading to ICD Intervention	umber of participants with ventricular arrhythmias leading to ICD therapy, including anti-tachycardia pacing or shock, during the study period. Unit of Measure: Number of Participants	3 months

Collaborators and Investigators

• Sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna

Study record dates

Study Major Dates

• Study Start (Estimated): July 15, 2026
• Primary Completion (Estimated): September 6, 2027
• Study Completion (Estimated): December 4, 2028

Study Registration Dates

• First Submitted: March 10, 2026
• First Submitted That Met QC Criteria: June 3, 2026
• First Posted (Actual): June 9, 2026

Study Record Updates

• Last Update Posted (Actual): June 9, 2026
• Last Update Submitted That Met QC Criteria: June 3, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Biomarkers; Congestion; Hearth failure
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure
• Other Study ID Numbers: BIOTOOL-CHF VALID; 101095653 (Other Grant/Funding Number: European Health and Digital Executive Agency)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No