Clinical trial NCT05747820: Multiparametric Assessment of Cardiac Congestion in Outpatient Worsening Heart Failure
Official title: Observational Study for Multiparametric Assessment of Cardiac Congestion in Outpatient Worsening Heart Failure (EVOLUTION)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Heart Failure
Heart Decompensation
Keywords: Worsening Heart Failure
Lead sponsor: Corteria Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2023-02-28
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Approximately 40 adult male and female patients with a diagnosis of HFrEF (EF\<40%) and HFmrEF (EF \>40 \< 50%) who had a hospital admission for HF within 1 to12 months prior to screening and developed worsening symptoms of HF during the week prior to presentation to an outpatient clinic.

Brief summary: This observational study is conducted to assess the evolution of multiple markers of congestion over 4 weeks after a worsening heart failure (WHF) event treated in an outpatient unit

Detailed description: This is a multicenter, non-randomized, observational study designed to assess the evolution of multiple markers (physical, echocardiographic, and biomarkers) of congestion in 40 patients with chronic heart failure (CHF) treated over 4 weeks with 40 to 120 mg daily oral furosemide after an event of WHF treated in an outpatient unit. Patients at selected centers may participate in a telemetry ancillary study, in which real-time, continuous, non-invasive measurements of physiologic parameters of heart failure will be obtained through use of a wearable medical telemetry device.

Approximately 40 patients with CHF with reduced or mildly reduced left ventricular ejection fraction (EF \< 50%) who had an admission for WHF in the preceding 1-12 months and who develop symptoms of WHF over the week before presentation to an outpatient clinic will be enrolled. Patients will attend five outpatient visits over the course of 4 weeks.

At each visit, the patient's vital signs will be measured, clinical assessments (NYHA class, jugular vein distension, peripheral edema score, pulmonary rales) will be performed, and blood samples for central assays will be obtained. Detailed echocardiographic examination will be performed prior to enrolment in the first visit and at Visit 5.

Biomarkers related to cardiac and renal function will be measured in blood and urine samples at each visit.

Eligibility criteria: Inclusion Criteria:

1. Male or female patients ≥ 18 and \< 80 years of age.
2. Previous documented hospital admission for HF between 12 months and 1 month prior to Screening.
3. Ambulatory patients with a diagnosis of stable NYHA class II - III HF with left ventricular ejection fraction \<50%, who experience a worsening of heart failure (WHF), with worsening signs and/or symptoms of heart failure requiring institution or up titration of loop diuretic therapy, in the week preceding their visit to the outpatient HF clinic and with at the time of Screening:

   1. Dyspnea and at least one symptom of congestion (rales, orthopnea, peripheral oedema)
   2. Imaging confirmation of congestion as defined by either pulmonary congestion on chest X-ray or at least 2 B-lines by lung ultrasound.
4. Stable oral doses of ACEi, ARB or ARNi, beta-blocker, mineralocorticoid antagonist (MRA), and SGLT2i for \> 1 month prior to screening.
5. An increase in the prescribed oral loop diuretic dose up to 120 mg daily furosemide or equivalent\*for the treatment of the WHF event.
6. Biomarker profile suggestive of significant HF inclusive of NT-proBNP ≥1500 pg/ml, and elevated TnT from 15 ng/L (0.015 mcg/L) to 150 ng/L (0.15 mcg/L) or equivalent TnI using ultrasensitive assay.
7. Mild to moderate renal impairment (eGFR by the simplified MDRD formula of \>30 and \<60 ml/min/1.73 m2).
8. Written informed consent to participate in the study.
9. Ability to comply with all study requirements, without major morbidities compromising the patient's ability to participate and understand the study for 90 days.

Exclusion Criteria:

1. Significant pulmonary disease contributing substantially to the patients' dyspnea such as FEV1\< 1 liter or need for chronic steroid therapy.
2. Myocardial infarction, unstable angina, ICD or CRT implantation, or cardiac surgery, including percutaneous transluminal coronary intervention, within past 3 months.
3. History of heart transplant or on a transplant list or using or planned to be implanted with a ventricular assist device.
4. Significant uncontrolled arrythmia such as atrial fibrillation with a persistent heart rate \> 120 beast/minute, any bradyarrhythmia with a persistent heart rate \< 50 beats/min, sustained supraventricular tachycardia, any evidence of tri-fascicular block by ECG.
5. Sustained ventricular arrhythmia with syncopal episodes within past 3 months that is untreated.
6. Presence of any hemodynamically moderate or severe valvular stenosis or regurgitation, except for moderate mitral or tricuspid regurgitation secondary to left ventricular dilatation. Presence of hemodynamically significant obstructive lesions of left ventricular outflow tract.
7. Stroke or TIA within the past 3 months.
8. Primary or alcoholic liver disease considered to be life threatening.
9. Any episode of symptomatic hypotension within 3 months prior to screening.
10. Coagulation or bleeding disorder.
11. Systolic blood pressure \< 100 mmHg or \>180 mmHg.
12. Serum sodium \> 146 mEq/L (146 mmol/L) or \<135 mEq/L
13. Serum potassium \> 5.2 mEq/L (5.2 mmol/L) or \< 3.5 mEq/L (3.5 mmol/ L).
14. Ultrafiltration or dialysis within 3 months prior to Screening.
15. Hypersensitivity to furosemide.
16. History or presence of any other diseases (i.e. including malignancies) with a life expectancy of \< 3 months.
17. Participation in any CHF trial or any investigational drug or device study within the 30 days prior to Screening.
18. History of noncompliance to medical regimens and patients who are considered potentially unreliable.
19. Pregnant or nursing (lactating) women.
20. Active infection based on abnormal temperature and/or elevated WBC count.
21. Any evidence of COVID -19 infection
22. Hemoglobin \<8 g/L or receipt of blood transfusion within 3 months prior to Screening.
23. Contraindication to the use of the wrist-worn telemetry device: skin problem or wound in the wrist area, inclusive of tattoos.

Primary outcomes:
measure: Change in E/e' ratio
timeFrame: Screening (Visit 1) and week 4 (beginning of Visit 5).
measure: Changes in Left Ventricular End-Diastolic Diameter (LVEDD)
timeFrame: From screening to 4 weeks
measure: Changes in Left Ventricular End-Systolic Diameter (LVESD)
timeFrame: From screening to 4 weeks
measure: Changes in Left Ventricular End-Diastolic Volume (LVEDV)
timeFrame: From screening to 4 weeks
measure: Changes in Left Ventricular End-Systolic Volume (LVESV)
timeFrame: From screening to 4 weeks
measure: Changes in Left Ventricular Ejection Fraction (LVEF)
timeFrame: From screening to 4 weeks
measure: Changes in mitral E-velocity
timeFrame: From screening to 4 weeks
measure: Changes in mitral A-velocity
timeFrame: From screening to 4 weeks
measure: Changes in E' velocity
timeFrame: From screening to 4 weeks
measure: Changes in Right Ventricular Systolic Pressure (RVSP)
timeFrame: From screening to 4 weeks
measure: Changes in Tricuspid Annular Pulmonary Systolic Excursion (TAPSE)
timeFrame: From screening to 4 weeks
measure: Changes in S' velocity
timeFrame: From screening to 4 weeks
measure: Changes in Inferior Vena Cava (IVC) diameter
timeFrame: From screening to 4 weeks
measure: Changes in Left Atrium (LA) surface
timeFrame: From screening to 4 weeks
measure: Changes in Right Atrium (RA) surface
timeFrame: From screening to 4 weeks
measure: Changes in patient-reported dyspnea
timeFrame: From screening to 4 weeks
measure: Changes in clinically-assessed jugular venous pulse
timeFrame: From screening to 4 weeks
measure: Changes in clinically-assessed peripheral edema
timeFrame: From screening to 4 weeks
measure: Changes in estimated Glomerular Filtration Rate (eGFR)
timeFrame: From screening to 4 weeks
measure: Changes in serum creatinine
timeFrame: From screening to 4 weeks
measure: Changes in NT-proBNP
timeFrame: From screening to 4 weeks
measure: Changes in high sensitivity Troponin T (HsTnT)
timeFrame: From screening to 4 weeks
measure: Changes in Kansas City Cardiomyopathy Questionnaire (KCCQ)-12
timeFrame: From screening to 4 weeks
measure: Weekly changes in telemetered parameters in patients wearing the wrist-worn device (Philips Health Band)
timeFrame: From screening to 4 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Yerevan
country: Armenia
facility: Institute of Cardiology Levon Hovhannisyan
city: Yerevan
country: Armenia
facility: Erebuni Medical Center
city: Banja Luka
country: Bosnia and Herzegovina
facility: Health Institution Medico Laser, Cardiology ward
city: Mostar
country: Bosnia and Herzegovina
facility: Universty Clinical Hospital Mostar, Clinic for Internal diseases with dyalisis center, Clinical ward for cardiology
Study officials:
affiliation: Hôpitaux Universitaires Saint-Louis-Lariboisière, University Paris Diderot, Inserm 942
name: Alexandre Mebazaa, MD
role: PRINCIPAL_INVESTIGATOR
References: