Screening for Advanced Heart Failure IN Stable ouTpatientS - The SAINTS Study

Heart Failure With Reduced Ejection Fraction Clinical Trial

— SAINTS-A  

Official title:

Screening for Advanced Heart Failure IN Stable ouTpatientS (The SAINTS Study) - Early Identification of Advanced Heart Failure

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05299879
• Other study ID #: RH-SAINTS-A
• Status: Recruiting
• Start date: October 24, 2022
• Est. completion date: December 2025

Study information

• Verified date: October 2022
• Source: Rigshospitalet, Denmark
• Contact: Finn Gustafsson, MD, PhD, DMSci
• Phone: +45 35459743
• Email: finng[@]dadlnet.dk
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

The purpose of the Screening for Advanced heart failure IN stable ouTpatientS (SAINTS) study is to determine the prevalence of advanced heart failure (HF) in symptomatic patients with HF and reduced left ventricular ejection fraction (HFrEF), corresponding to the New York Heart Association functional class II-III.

Recognition of advanced HF is a challenge for physicians and under referral for advanced management is a considerable problem. There are excellent treatment options for patients with advanced HF, i.e. heart transplantation or left ventricular assist device (LVAD) implantation, and outcomes with these therapies are considerably better if patients are treated before irreversible end-organ damage occurs. International consensus highlights the importance of timely recognition and referral of these patients to advanced HF centers.

The investigators aim to screen patients with symptomatic HFrEF who are followed in Danish HF clinics in the Copenhagen region with echocardiography, cardiopulmonary exercise test, 6 minute walk test, and NT-proBNP. The investigators hypothesize that 20% of patients with symptomatic heart failure followed in HF clinics in the Copenhagen Region will fulfill the modified criteria for advanced HF from the HFA-ESC (primary end-point in the study)(Reference 1). Patients who are identified with advanced HF will be offered right heart catheterization, guided by ultrasound and inserted through the internal jugular vein, determining pulmonary capillary wedge pressure, cardiac index, central venous pressure, mean pulmonary artery pressure, and central venous oxygen saturation. Patients not fulfilling criteria for advanced HF will be offered right heart catheterization consecutively until 50 patients have been examined (this group will be a comparator group to the patients with advanced HF).

Patients identified with advanced HF will be offered listing for HTx or LVAD if an indication without a contraindication is present. Patients who fulfill the primary endpoint of modified HFA-ESC criteria for advanced HF, and are ineligible for, or unwilling to undergo HTx or LVAD implantation will be invited to participate in the SAINTS B study.

Description:

Number of patients and sample size More than 3000 patients are followed in the HF clinics on Zealand including the greater Copenhagen region. The investigators plan to include 400 patients in the primary outcome analysis (SAINTS A) and hypothesize that 20% will fulfill the modified criteria for advanced HF.

Statistical analysis Descriptive statistics will be reported as mean +/- standard deviation (SD) or median (interquartile range (IQR)) depending on distribution. Comparisons between groups at baseline will be performed by unpaired t-tests for normally distributed continuous variables, by the Mann-Whitney U test (Wilcoxon rank-sum) for non-normally distributed continuous variables and χ2 or Fisher's exact test for categorical variables.

The primary outcome will be analyzed as the proportion n (%) of included patients who fulfill the modified HFA-ESC criteria for advanced HF. As for secondary outcomes, the investigators will analyze the proportion n (%) of patients who within the first 3 months are; 1) offered heart transplant listing, 2) offered LVAD implantation, 3) listed for HTx and 4) undergoing LVAD implantation. Further, comparisons of invasive hemodynamics, CPET measures, 6MWT, QoL and NTproBNP levels between patients with and without advanced HF will be made using an unpaired t-test or the Mann-Whitney U test for non-normally distributed continuous variables.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 400
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years to 74 Years

Eligibility

Inclusion Criteria:

1. History of Chronic heart failure > 3 months

2. Stable (no hospitalization last 3 months) NYHA functional class II-III

3. HFrEF patients (Left ventricular ejection fraction (LVEF) = 30%)

4. On or attempted betablocker and Renin-Angiotensin System (RAS) inhibitor treatment

5. Informed consent

Exclusion Criteria:

1. Body Mass Index (BMI) > 40 kg/m2

2. Chronic renal replacement therapy or estimated Glomerular Filtration Rate (eGFR) < 15 ml/min/1.73m2

3. Cardiac Resynchronization Therapy (CRT) implantation < 3 months ago or planned CRT

4. Severe primary valvular disease

5. On waiting list for heart transplantation or referred for evaluation

6. Cancer or other severe non-cardiac disease with estimated life expectancy less than 1 year

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure With Reduced Ejection Fraction

Intervention

Diagnostic Test:
• Cardiopulmonary exercise test, NT-proBNP, Echocardiography, 6 minute walk test, Right heart catheterization
Screening for advanced HF with modified criteria from the Heart Failure Association of the European Society of Cardiology

Locations

Country	Name	City	State
Denmark	Amager/Hvidovre Hospital	Copenhagen
Denmark	Bispebjerg-Frederiksberg Hospital	Copenhagen
Denmark	Herlev and Gentofte Hospital	Copenhagen
Denmark	Glostrup Hospital	Glostrup
Denmark	Nordsjællands Hospital Hillerød	Hillerød
Denmark	Zeeland University Hospital Roskilde	Roskilde

Sponsors (2)

Lead Sponsor	Collaborator
Rigshospitalet, Denmark	Novo Nordisk A/S

Country where clinical trial is conducted

Denmark, 

References & Publications (1)

Crespo-Leiro MG, Metra M, Lund LH, Milicic D, Costanzo MR, Filippatos G, Gustafsson F, Tsui S, Barge-Caballero E, De Jonge N, Frigerio M, Hamdan R, Hasin T, Hülsmann M, Nalbantgil S, Potena L, Bauersachs J, Gkouziouta A, Ruhparwar A, Ristic AD, Straburzynska-Migaj E, McDonagh T, Seferovic P, Ruschitzka F. Advanced heart failure: a position statement of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2018 Nov;20(11):1505-1535. doi: 10.1002/ejhf.1236. Epub 2018 Jul 17. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients screened who fulfill advanced HF criteria using a modified HFA-ESC definition	Modified HFA-ESC criteria for advanced HF defined as: • LVEF = 30% as estimated by echocardiography; AND; • Peak oxygen uptake (VO2peak) < 12 ml/kg/min (14 if on betablocker) with a Respiratory Exchange Ratio (RER) > 1.05 OR < 50% expected for age and gender OR 6 minute walk test (6MWT) distance < 300 meters; AND; • N-terminal pro B-type natriuretic peptide (NTproBNP) > 2000 pg / ml	At time of screening
Secondary	Proportion of patients offered heart transplant listing < 3 months after primary outcome		3 months after meeting modified HFA-ESC criteria for advanced HF
Secondary	Proportion of patients offered LVAD implantation < 3 months after primary outcome		3 months after meeting modified HFA-ESC criteria for advanced HF
Secondary	Proportion of patients listed for heart transplantation < 3 months after primary outcome		3 months after meeting modified HFA-ESC criteria for advanced HF
Secondary	Proportion of patients undergoing LVAD implantation < 3 months after primary outcome		3 months after meeting modified HFA-ESC criteria for advanced HF
Secondary	Pulmonary capillary wedge pressure (PCWP) in mmHg compared between patients with, and without advanced HF	Measured during right heart catheterization	Within 30 days from screening
Secondary	Cardiac index (CI) in l/min/m2 compared between patients with, and without advanced HF	Measured during right heart catheterization	Within 30 days from screening
Secondary	Central venous pressure (CVP) in mmHg compared between patients with, and without advanced HF	Measured during right heart catheterization	Within 30 days from screening
Secondary	Mean pulmonary artery pressure (mPAP) in mmHg compared between patients with, and without advanced HF	Measured during right heart catheterization	Within 30 days from screening
Secondary	Central venous oxygen saturation in % compared between patients with, and without advanced HF	Measured during right heart catheterization	Within 30 days from screening
Secondary	Peak oxygen uptake (VO2peak) in ml/kg/min compared between patients with, and without advanced HF	Measured during cardiopulmonary exercise test	At time of screening
Secondary	Peak respiratory exhange ratio compared between patients with, and without advanced HF	The ratio between metabolic production of CO2 and the uptake of O2 measured during cardiopulmonary exercise test	At time of screening
Secondary	Minute ventilation-to-carbon dioxide output slope (VE/VCO2) compared between patients with, and without advanced HF	The ratio between metabolic production of CO2 and the uptake of O2 measured during cardiopulmonary exercise test	At time of screening
Secondary	Peak Borg scale score compared between patients with, and without advanced HF	The Borg scale score is a rating of perceived exertion on a scale from 6-20, with 6 representing at rest, and 20 the most strenuous exercise imaginable. Measured during cardiopulmonary exercise test	At time of screening
Secondary	6 minute walk test compared between patients with, and without advanced HF		At screening
Secondary	Quality of Life (Kansas City Cardiomyopathy Questionnaire (KCCQ)		At screening
Secondary	NT-proBNP compared between patients with, and without advanced HF		At screening