## Protocol Section
### Identification Module
**NCT ID:** NCT05299879

**Acronym:** SAINTS-A

**Brief Title:** Screening for Advanced Heart Failure IN Stable ouTpatientS - The SAINTS Study

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

#### Organization Study ID Info
**ID:** RH-SAINTS-A
#### Organization
**Class:** OTHER
**Full Name:** Rigshospitalet, Denmark
### Status Module
#### Completion Date
**Date:** 2025-12

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2022-11-01

**Type:** ACTUAL

**Last Update Submit Date:** 2022-10-31

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2025-12

**Type:** ESTIMATED

#### Start Date
**Date:** 2022-10-24

**Type:** ACTUAL

**Status Verified Date:** 2022-10

#### Study First Post Date
**Date:** 2022-03-29
**Type:** ACTUAL
**Study First Submit Date:** 2022-03-07
**Study First Submit QC Date:** 2022-03-18
### Sponsor Collaborators Module

#### Collaborators

**Class:** INDUSTRY

**Name:** Novo Nordisk A/S

#### Lead Sponsor

**Class:** OTHER

**Name:** Rigshospitalet, Denmark

#### Responsible Party

**Investigator Affiliation:** Rigshospitalet, Denmark

**Investigator Full Name:** Finn Gustafsson

**Investigator Title:** Sponsor-Investigator

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief 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.

**Detailed 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.

### Conditions Module

**Conditions:**

- Heart Failure With Reduced Ejection Fraction

**Keywords:**

- Advanced heart failure

- Screening

### Design Module

#### Bio Spec

**Description:** Full blood

**Retention:** SAMPLES_WITH_DNA

#### Design Info

**Observational Model:** COHORT

**Time Perspective:** PROSPECTIVE

#### Enrollment Info

**Count:** 400

**Type:** ESTIMATED

**Patient Registry:** True

**Study Type:** OBSERVATIONAL

**Target Duration:** 3 Months

### Arms Interventions Module

#### Arm Group 1

**Intervention Names:**

- Diagnostic Test: Cardiopulmonary exercise test, NT-proBNP, Echocardiography, 6 minute walk test, Right heart catheterization

**Label:** Symptomatic patients with HFrEF corresponding to NYHA II-III

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Symptomatic patients with HFrEF corresponding to NYHA II-III

**Description:** Screening for advanced HF with modified criteria from the Heart Failure Association of the European Society of Cardiology

**Name:** Cardiopulmonary exercise test, NT-proBNP, Echocardiography, 6 minute walk test, Right heart catheterization

**Type:** DIAGNOSTIC_TEST

### Outcomes Module

#### Primary Outcomes

**Description:** 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

**Measure:** Proportion of patients screened who fulfill advanced HF criteria using a modified HFA-ESC definition

**Time Frame:** At time of screening

#### Secondary Outcomes

**Measure:** Proportion of patients offered heart transplant listing < 3 months after primary outcome

**Time Frame:** 3 months after meeting modified HFA-ESC criteria for advanced HF

**Measure:** Proportion of patients offered LVAD implantation < 3 months after primary outcome

**Time Frame:** 3 months after meeting modified HFA-ESC criteria for advanced HF

**Measure:** Proportion of patients listed for heart transplantation < 3 months after primary outcome

**Time Frame:** 3 months after meeting modified HFA-ESC criteria for advanced HF

**Measure:** Proportion of patients undergoing LVAD implantation < 3 months after primary outcome

**Time Frame:** 3 months after meeting modified HFA-ESC criteria for advanced HF

**Description:** Measured during right heart catheterization

**Measure:** Pulmonary capillary wedge pressure (PCWP) in mmHg compared between patients with, and without advanced HF

**Time Frame:** Within 30 days from screening

**Description:** Measured during right heart catheterization

**Measure:** Cardiac index (CI) in l/min/m2 compared between patients with, and without advanced HF

**Time Frame:** Within 30 days from screening

**Description:** Measured during right heart catheterization

**Measure:** Central venous pressure (CVP) in mmHg compared between patients with, and without advanced HF

**Time Frame:** Within 30 days from screening

**Description:** Measured during right heart catheterization

**Measure:** Mean pulmonary artery pressure (mPAP) in mmHg compared between patients with, and without advanced HF

**Time Frame:** Within 30 days from screening

**Description:** Measured during right heart catheterization

**Measure:** Central venous oxygen saturation in % compared between patients with, and without advanced HF

**Time Frame:** Within 30 days from screening

**Description:** Measured during cardiopulmonary exercise test

**Measure:** Peak oxygen uptake (VO2peak) in ml/kg/min compared between patients with, and without advanced HF

**Time Frame:** At time of screening

**Description:** The ratio between metabolic production of CO2 and the uptake of O2 measured during cardiopulmonary exercise test

**Measure:** Peak respiratory exhange ratio compared between patients with, and without advanced HF

**Time Frame:** At time of screening

**Description:** The ratio between metabolic production of CO2 and the uptake of O2 measured during cardiopulmonary exercise test

**Measure:** Minute ventilation-to-carbon dioxide output slope (VE/VCO2) compared between patients with, and without advanced HF

**Time Frame:** At time of screening

**Description:** 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

**Measure:** Peak Borg scale score compared between patients with, and without advanced HF

**Time Frame:** At time of screening

**Measure:** 6 minute walk test compared between patients with, and without advanced HF

**Time Frame:** At screening

**Measure:** Quality of Life (Kansas City Cardiomyopathy Questionnaire (KCCQ)

**Time Frame:** At screening

**Measure:** NT-proBNP compared between patients with, and without advanced HF

**Time Frame:** At screening

### Eligibility Module

**Eligibility Criteria:** 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

**Maximum Age:** 74 Years

**Minimum Age:** 19 Years

**Sampling Method:** NON_PROBABILITY_SAMPLE

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

**Study Population:** Patients followed in Danish HF clinics in the Copenhagen region.

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** finng@dadlnet.dk

**Name:** Finn Gustafsson, MD, PhD, DMSci

**Phone:** +45 35459743

**Role:** CONTACT

**Contact 2:**

**Email:** johanlarsson923@gmail.com

**Name:** Johan Larsson, MD

**Phone:** +45 50298907

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Copenhagen

**Contacts:**

***Contact 1:***

- **Name:** Olav Wendelbo Nielsen, MD, ph.d, dr.med.

- **Role:** CONTACT

**Country:** Denmark

**Facility:** Bispebjerg-Frederiksberg Hospital

**Status:** NOT_YET_RECRUITING

**Zip:** 2400

**Location 2:**

**City:** Copenhagen

**Contacts:**

***Contact 1:***

- **Name:** Morten Petersen, MD, ph.d

- **Role:** CONTACT

**Country:** Denmark

**Facility:** Amager/Hvidovre Hospital

**Status:** NOT_YET_RECRUITING

**Zip:** 2650

**Location 3:**

**City:** Copenhagen

**Contacts:**

***Contact 1:***

- **Name:** Morten Schou, MD, ph.d

- **Role:** CONTACT

**Country:** Denmark

**Facility:** Herlev and Gentofte Hospital

**Status:** NOT_YET_RECRUITING

**Zip:** 2730

**Location 4:**

**City:** Glostrup

**Contacts:**

***Contact 1:***

- **Name:** Anders Barasa, MD, ph.d

- **Role:** CONTACT

**Country:** Denmark

**Facility:** Glostrup Hospital

**Status:** RECRUITING

**Zip:** 2600

**Location 5:**

**City:** Hillerød

**Contacts:**

***Contact 1:***

- **Name:** Nis Stride, MD, ph.d

- **Role:** CONTACT

**Country:** Denmark

**Facility:** Nordsjællands Hospital Hillerød

**Status:** NOT_YET_RECRUITING

**Zip:** 3400

**Location 6:**

**City:** Roskilde

**Contacts:**

***Contact 1:***

- **Name:** Nadia Dridi

- **Role:** CONTACT

**Country:** Denmark

**Facility:** Zeeland University Hospital Roskilde

**Status:** NOT_YET_RECRUITING

**Zip:** 4000

#### Overall Officials

**Official 1:**

**Affiliation:** Rigshospitalet, Denmark

**Name:** Finn Gustafsson, MD, PhD, DMSci

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** UNDECIDED

### References Module

#### References

**Citation:** 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, Hulsmann 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.

**PMID:** 29806100

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000006331

- Term: Heart Diseases

- ID: D000002318

- Term: Cardiovascular Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC14

- Name: Heart and Blood Diseases

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M9421

- Name: Heart Failure

- Relevance: HIGH

- As Found: Heart Failure

- ID: M9419

- Name: Heart Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000006333

- Term: Heart Failure

### Misc Info Module

- Version Holder: 2024-05-24
