BIOmarker Based Diagnostic TOOLkit to Personalize Pharmacological Approaches in Congestive Heart Failure

BIOmarker Based Diagnostic TOOLkit to Personalize Pharmacological Approaches in Congestive Heart Failure Discovery - a BIOSTAT-CHF Substudy BIOTOOL-CHF DISCO

This retrospective study will take advantage of an existing EU-funded dataset, the BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF), which was designed to identify biomarkers related to the response to guideline directed medical therapy, and coordinated by UMCG.

The availability of this comprehensive dataset of patients with severe HFrEF, prospectively and consistently collected, with the possibility to access a biobank to re-assay samples with novel biomarkers, provides a unique opportunity to derive preliminary data about the interaction between biomarkers of congestion and diuretic doses, that were prescribed based on clinical judgement, and therefore derive a machine learning-based algorithm than could be tested to guide the management of diuretic therapy

Study Overview

• Status: Active, not recruiting
• Conditions: Heart Failure With Reduced Ejection Fraction (HFrEF); Congestive Heart Failure(CHF)

Detailed Description

This is a retrospective study based on the index and the validation cohorts of the BIOSTAT-CHF project. The index cohort consists of a prospectively enrolled series of 2516 patients from 69 centres in 11 European countries recruited between December 2010 and December 2012 and with a median follow-up of 21 months [interquartile range (IQR) 15 - 27 months]. Validation cohort was designed as well as a multicentre, prospective, observational study, which included 1738 patients from six centres in Scotland, United Kingdom.

BIOSTAT-CHF samples and data will be re-analysed to include additional congestion biomarkers, to obtain the BIOTOOL-CHF DISCO dataset. The latter has been used to derive a predictive model for congestion-related adverse events, priming the design of a prospective randomized study (the BIOTOOL-CHF VALID study).

Preliminary analysis reported advanced age, higher blood urea nitrogen and N-terminal pro-B-type natriuretic peptide (NT-proBNP), lower haemoglobin, and failure to prescribe a beta-blocker as the five strongest predictors of mortality. Moreover, the five strongest predictors of hospitalisation due to decompensated HF were more advanced age, previous hospitalisation owing to HF, presence of oedema, lower systolic blood pressure and lower estimated glomerular filtration rate.

Capitalizing from these preliminary results, the BIOTOOL-CHF VALID study will test the score derived from the analysis of the BIOTOOL-CHF DISCO dataset, in order to guide therapy management in HF patients.

• Study Type: Observational
• Enrollment (Actual): 4254

Contacts and Locations

Study Locations

• Italy
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40138
      • Heart Failure and Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

The study population will be patients with congestive HF previously enrolled in the BIOSTAT-CHF cohorts. The index cohort consists of a prospectively enrolled series of 2516 patients from 69 centres in 11 European countries recruited between December 2010 and December 2012 and with a median follow-up of 21 months [interquartile range (IQR) 15 - 27 months]. Validation cohort was designed as well as a multicentre, prospective, observational study, which included 1738 patients from six centres in Scotland, United Kingdom

Description

Inclusion Criteria:

In order to have been included to participate in the index trial, a subject must have met all of the following criteria:

• age >=18 years with symptoms of new-onset or worsening heart failure;
• objective evidence of cardiac dysfunction documented either by left ventricular ejection fraction <=40% or plasma concentrations of brain natriuretic peptide (BNP) >400 pg/mL and/or NT-proBNP >2000 pg/mL;
• treatment with either oral or intravenous furosemide >=40 mg/day or equivalent at the time of inclusion; not previously treated with evidence-based therapies (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and beta-blockers) or receiving <=50% of target doses of these drugs at the time of inclusion; anticipated initiation or up-titration of ACE inhibitors or ARBs and/or beta-blockers by the treating physician.

For the validation cohort, patients had to fulfil the following inclusion criteria:

• age >=18 years;
• diagnosis of heart failure with a previous documented admission requiring diuretic treatment;
• treatment with furosemide >=20 mg/day or equivalent;
• not previously treated or receiving <=50% of target doses of ACE inhibitors or ARBs and/or beta-blockers;
• anticipated initiation or up-titration of ACE inhibitors or ARBs and/or beta-blockers. In both trials, patients could be enrolled as inpatients or from outpatient clinics.

Exclusion Criteria:

A potential subject who meets any of the following criteria will be excluded from participation in this study:

- known diagnosis of septicaemia, known diagnosis of acute myocarditis or hypertrophic obstructive, restrictive, or constrictive cardiomyopathy, heart transplant recipient or admitted for cardiac transplantation or left ventricular assist device surgery, anticipated need for surgery or any cardiovascular intervention, except implantable cardioverter defibrillator and-or cardiac resynchronization therapy, within 4 weeks, current known inability to follow instructions or comply with follow-up procedures, and treatment with medications or devices not approved in Europe.

Patients with concomitant pulmonary disease, even if severe, valvular disease, acute coronary syndrome or stroke, could be included when the primary diagnosis for admission to hospital or outpatient clinic visit was heart failure, rather than the concomitant condition

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Validation cohort
Index cohort

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary endpoint of the study will be time to death or first-hospitalisation for HF in the nine months after study entry	9 month

Secondary Outcome Measures

Outcome Measure	Time Frame
- Variability in the congestion score assessed from baseline to Month 9 - Variability in the Kansas City Cardiomyopathy Questionnaire from baseline to month 9	9 months

Collaborators and Investigators

• Sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna

Publications and helpful links

General Publications

• Voors AA, Anker SD, Cleland JG, Dickstein K, Filippatos G, van der Harst P, Hillege HL, Lang CC, Ter Maaten JM, Ng L, Ponikowski P, Samani NJ, van Veldhuisen DJ, Zannad F, Zwinderman AH, Metra M. A systems BIOlogy Study to TAilored Treatment in Chronic Heart Failure: rationale, design, and baseline characteristics of BIOSTAT-CHF. Eur J Heart Fail. 2016 Jun;18(6):716-26. doi: 10.1002/ejhf.531. Epub 2016 Apr 29.

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2024
• Primary Completion (Actual): February 20, 2025
• Study Completion (Estimated): January 10, 2034

Study Registration Dates

• First Submitted: March 10, 2026
• First Submitted That Met QC Criteria: March 10, 2026
• First Posted (Actual): March 13, 2026

Study Record Updates

• Last Update Posted (Actual): May 7, 2026
• Last Update Submitted That Met QC Criteria: May 4, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Biomarkers; Congestion; Score
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure
• Other Study ID Numbers: BIOTOOL-CHF DISCO; 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