Clinical trial NCT06459999: Biomarkers for the Assessment of Congestion in Patients With Ambulatory and Hospitalised Heart Failure
Official title: Biomarkers for the Assessment of Congestion in Patients With Ambulatory and Hospitalised Heart Failure
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Heart Failure
Congestion
Lead sponsor: NHS Greater Glasgow and Clyde
Sponsor class: OTHER
Collaborators: name: University of Glasgow
name: Roche Diagnostics GmbH
First posted: 2024-06-14
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Cohort A: patients with heart failure (HF) undergoing clinically indicated right heart catheterisation (RHC) +/- clinically-indicated repeat RHC in the Scottish Advanced Heart Failure Service (SNAHFS).

Cohort B: patients with HF undergoing RHC during implantation of a cardiac resynchronisation therapy (CRT) device.

Cohort C: patients hospitalised with HF receiving intravenous (IV) diuretic therapy.

Brief summary: The goal of this study is to test the accuracy of new blood and urine tests in people with heart failure. The main question it aims to answer is:

- Do new blood and urine tests correlate with fluid status? This will be determined by comparison to routine and gold-standard tests in a range of patients with heart failure.

Detailed description: Heart failure (HF) is a common condition that is associated with recurrent and prolonged hospital admissions (hospitalisation). HF hospitalisation is associated with poor outcomes and therefore the identification of patients at risk of HF hospitalisation, and avoidance of these events, is of great importance.

HF hospitalisations are frequently preceded by a period of increasing congestion (pressure elevation within heart chambers and excess body fluid). The identification of congestion can be difficult. Current tests have limitations and signs of congestion such as lung crackles or leg swelling that can be recognised by health care professionals are often seen at a late stage before an intervention can be made to prevent hospitalisation. Reliably identifying congestion prior to the development of these signs would facilitate earlier intervention (treatment to de-congest) and may prevent hospitalisations. Patients who do require hospital admission are often discharged with residual congestion which is associated with readmission and increased risk of death. Tests that correlate closely with the degree of congestion and track with decongestion could guide therapy and help with decision-making about suitability for hospital discharge.

The investigators propose to recruit 140 patients. Patients will be identified during hospitalisation with HF or prior to implantation of a cardiac resynchronisation therapy (CRT) device. Each patient will have a history, physical examination, electrocardiogram (ECG), echocardiogram (cardiac ultrasound) and lung ultrasound performed. Some patients will have a procedure to record pressure measurements within the heart (right heart catheterisation) if clinically indicated as routine care. Blood and urine tests will also be taken.

The aim of this study is to evaluate the accuracy of novel blood and urine tests at measuring congestion compared with standard assessments. This may help in the discovery and development of new and improved tests for assessing congestion.

Eligibility criteria: Inclusion Criteria:

* Written informed consent.
* Male or female ≥18 years of age.
* Cohort A

  * Meet European Society of Cardiology (ESC) criteria for diagnosis of HF1, including HF with reduced (HFrEF), mildly reduced (HFmrEF) and preserved ejection fractions (HFpEF).
  * Hospitalised for the management of HF or outpatients.
  * Undergoing clinically-indicated RHC or repeat clinically-indicated RHC.
* Cohort B

  * Meet ESC criteria for diagnosis of HFrEF.
  * Undergoing implantation of CRT device and a simultaneous clinically-indicated RHC.
* Cohort C

  * Meet ESC criteria for diagnosis of HF, including HFrEF, HFmrEF, HFpEF.
  * Requiring treatment with IV diuretics.

Exclusion Criteria:

* Unwilling to consent.
* Unable to consent to inclusion in study due to cognitive impairment.
* Previously enrolled in the BIO-CONGEST study.
* Current participation in a blinded drug interventional trial (or treatment within four weeks).
* Pregnancy or breast-feeding (cohorts A + B where applicable).
* Currently uncontrolled cardiac arrhythmia.
* Severe aortic valvular disease.
* Increased body mass index where satisfactory echocardiographic images are not possible.
* Conditions that may confound congestion assessments in the opinion of the investigator, including: severe obstructive lung disease, severe fibrotic lung disease, severe liver disease, relevant active malignancy including lung cancer, pelvic cancer with caval compression, superior vena cava (SVC) obstruction syndrome, active viral or bacterial bronchopneumonia - chest x-ray (CXR) within four weeks showing consolidation, pulmonary contusion, pneumothorax, pneumonectomy, lobectomy, pulmonary embolism within the previous three months, indwelling intercostal chest drain, left ventricular assist device (LVAD), COVID-19 infection, type-1 acute myocardial infarction.

Primary outcomes:
measure: Correlation between concentrations of circulating biomarkers of congestion and pulmonary capillary wedge pressure (PCWP) and right atrial pressure (RAP).
timeFrame: 18 months
measure: Correlation of change in congestion measured by concentrations of circulating biomarkers of congestion and change in lung ultrasound (LUS)
timeFrame: 18 months
measure: Correlation of change in congestion measured by concentrations of circulating biomarkers of congestion and change in weight.
timeFrame: 18 months
Secondary outcomes:
measure: Correlation between congestion measured by concentrations of circulating biomarkers of congestion and physical signs (including EVEREST clinical congestion score [ECCS] and degree of pulmonary oedema).
timeFrame: 18 months
measure: Correlation between congestion measured by concentrations of circulating biomarkers of congestion and LUS.
timeFrame: 18 months
measure: Correlation between congestion measured by concentrations of circulating biomarkers of congestion and transthoracic echocardiography (TTE).
timeFrame: 18 months
measure: Correlation of change in congestion measured by change in concentrations of circulating biomarkers and change in congestion measured by physical signs (including ECCS and degree of pulmonary oedema).
timeFrame: 18 months
measure: Correlation of change in congestion measured by change in concentrations of circulating biomarkers and change in congestion measured by TTE.
timeFrame: 18 months
measure: Correlation between congestion measured by TTE and PCWP and RAP.
timeFrame: 18 months
measure: Correlation between congestion measured by LUS and PCWP and RAP.
timeFrame: 18 months
Other outcomes:
measure: Correlation between concentrations of circulating biomarkers of congestion and measures derived from RHC: right ventricle (RV) pressure, pulmonary artery (PA) pressure.
timeFrame: 18 months
measure: Correlation between change in concentrations of circulating biomarkers of congestion and change in other measures of congestion (as description below).
timeFrame: 18 months
measure: Regression analyses between frequency of rehospitalization or death and circulating biomarkers of congestion during hospital admission.
timeFrame: 18 months
Locations:
city: Clydebank
country: United Kingdom
facility: Golden Jubilee National Hospital
city: Glasgow
country: United Kingdom
facility: Queen Elizabeth University Hospital
Study officials:
affiliation: University of Glasgow
name: Kieran F Docherty, MBChB, PhD
role: PRINCIPAL_INVESTIGATOR
References: