UMIN-CTR Clinical Trial

Public title

Single-center prospective observational study investigating the impact of chronic inflammation on drug responsiveness in heart failure patients

Acronym

Observational study of heart failure patients with chronic inflammation

Scientific Title

Single-center prospective observational study investigating the impact of chronic inflammation on drug responsiveness in heart failure patients

Scientific Title:Acronym

Observational study of heart failure patients with chronic inflammation

Region

Japan

Condition

Chronic heart failure with preserved ejection fraction

Classification by specialty

Cardiology

Classification by malignancy

Others

Genomic information

YES

Narrative objectives1

Chronic inflammation is known to be involved in the pathogenesis of heart failure. The purpose of this study is to investigate the association between the degree of chronic inflammation and the efficacy of drug therapy in heart failure patients.

Basic objectives2

Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Developmental phase

Primary outcomes

Hospitalization for worsening heart failure (including unscheduled visits or intravenous diuretic use in the emergency setting)

Key secondary outcomes

1) Change in NT-proBNP from baseline
2) Changes in inflammation-related proteome
3) Changes in serum metabolome
4) Incidence of adverse events

Study type

Observational

Basic design

Randomization

Randomization unit

Blinding

Control

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

Purpose of intervention

Type of intervention

Interventions/Control_1

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

45

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

Inclusion criteria:
1. Men and women => 45 years of age
2. Patients with no prior treatment with SGLT2 inhibitors
3. Signs and symptoms of heart failure (HF) in the judgment of the investigator
and
a. Stable New York Heart Association (NYHA) II-IV symptoms.
b. Ejection fraction (EF) => 40% (stratified maximum 2/3 of patients in either 40-49% or =>50% groups) at the time of HF signs and symptoms or thereafter, less than 24 months prior to enrollment.
c. And at least one of the following objective criteria of HF:

i. Elevated NT-proBNP or BNP in the last 1 year defined as:
Measured as outpatient: NTproBNP => 300 ng/L or BNP => 75 ng/L with sinus rhythm; NTproBNP => 750 ng/L or BNP => 200 ng/L with atrial fibrillation (AF)
Measured when hospitalized acutely: NTproBNP => 500 ng/L or BNP => 125 ng/L with sinus rhythm, NT-proBNP => 1250 ng/L or BNP => 350 ng/L with AF.

ii. Hospitalization with HF as primary cause in last 12 months and structural heart disease on echocardiography according to ESC guidelines (i.e., either enlarged left atrial volume index (LAVI > 34 ml/m2) or increased left ventricular mass index (LVMI > 95 g/m2 in women and > 115 g/m2 in men).

iii. Pulmonary capillary wedge pressure (PCWP) at rest >15 mmHg or > 25 mmHg with exercise.

iv. E/e' ratio => 15 at rest on Doppler and tissue Doppler imaging.

Key exclusion criteria

Key Exclusion criteria:
1. Life expectancy < 3 years due to non-cardiovascular reasons.
2. Current decompensated HF.
3. Primary cardiomyopathy (e.g., constrictive, restrictive, infiltrative, toxic, hypertrophic (genetic), congenital, or any primary cardiomyopathy in judgment of investigator).
4. Current hemodynamically significant valve disease in opinion of investigator.
5. Any condition with indication for cardiac surgery or catheter intervention.
6. EF ever documented < 40%.
7. Any event (e.g., acute myocardial infarction) that may have reduced EF, that occurred after the echocardiogram used for inclusion, unless repeat echocardiogram confirms EF => 40%.
8. Tachycardia > 110 beats/min at screening.
9. Any current life-threatening dysrhythmia.
10. Probable alternative primary reason for patient's symptoms in judgment of investigator, including but not limited to:
a. Isolated pulmonary arterial hypertension or right ventricular (RV) failure; in the absence of left-sided HF.
b. Anemia (hemoglobin < 10 g/dl).
c. Severe chronic obstructive pulmonary disease (COPD) or lung disease (chronic oxygen use, nebulizer use, or oral steroid therapy).
11. Estimated glomerular filtration rate < 30 ml/min/1.73m2 (based on the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation), or on dialysis.
12. Alanine transaminase (ALT) or aspartate aminotransferase (AST) => 3x upper limit of normal (ULN). Resampling is not allowed during the same screening period if detected abnormal values do not have reasonable explanation and are not expected to return to normal level within few days.

Target sample size

100

Name of lead principal investigator

1st name	Junichi
Middle name
Last name	Kawakami

Organization

Hamamatsu University School of Medicine

Division name

Hospital Pharmacy

Zip code

431-3192

Address

1-20-1 Handayama, Chuo-ku, Hamamatsu City, Shizuoka Prefecture

TEL

053-435-2767

Email

kojisuzu@hama-med.ac.jp

Name of contact person

1st name	Koji
Middle name
Last name	Suzuki

Organization

Hamamatsu University School of Medicine

Division name

Hospital Pharmacy

Zip code

431-3192

Address

1-20-1 Handayama, Chuo-ku, Hamamatsu City, Shizuoka Prefecture

TEL

053-435-2767

Homepage URL

Email

kojisuzu@hama-med.ac.jp

Institute

Hamamatsu University School of Medicine

Institute

Department

Personal name

Organization

Hamamatsu University School of Medicine

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Ethics Committee of Hamamatsu University School of Medicine (EC HUSM)

Address

1-20-1 Handayama, Chuo-ku, Hamamatsu City, Shizuoka Prefecture

Tel

053-435-2680

Email

rinri@hama-med.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

浜松医科大学医学部附属病院

Date of disclosure of the study information

2024

Year

04

Month

05

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Enrolling by invitation

Date of protocol fixation

2023

Year

11

Month

01

Day

Date of IRB

2023

Year

12

Month

04

Day

Anticipated trial start date

2024

Year

04

Month

01

Day

Last follow-up date

2030

Year

03

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Study Design:
Single-center prospective observational study

Objective:
The aim of this study is to perform proteomic analysis, including inflammation-related molecules, in SGLT2 inhibitor-naive patients with HFpEF, to conduct molecular subtyping based on the results, and to compare responsiveness to SGLT2 inhibitor therapy among the identified subtypes.

Inclusion criteria:
1. Men and women => 45 years of age
2. Patients with no prior treatment with SGLT2 inhibitors
3. Signs and symptoms of heart failure (HF) in the judgment of the investigator
and
a. Stable New York Heart Association (NYHA) II-IV symptoms.
b. Ejection fraction (EF) => 40% (stratified maximum 2/3 of patients in either 40-49% or =>50% groups) at the time of HF signs and symptoms or thereafter, less than 24 months prior to enrollment.
c. And at least one of the following objective criteria of HF:

i. Elevated NT-proBNP or BNP in the last 1 year defined as:
Measured as outpatient: NTproBNP => 300 ng/L or BNP => 75 ng/L with sinus rhythm; NTproBNP => 750 ng/L or BNP => 200 ng/L with atrial fibrillation (AF)
Measured when hospitalized acutely: NTproBNP => 500 ng/L or BNP => 125 ng/L with sinus rhythm, NT-proBNP => 1250 ng/L or BNP => 350 ng/L with AF.
ii. Hospitalization with HF as primary cause in last 12 months and structural heart disease on echocardiography according to ESC guidelines (i.e., either enlarged left atrial volume index (LAVI > 34 ml/m2) or increased left ventricular mass index (LVMI > 95 g/m2 in women and > 115 g/m2 in men).
iii. Pulmonary capillary wedge pressure (PCWP) at rest >15 mmHg or > 25 mmHg with exercise.
iv. E/e' ratio => 15 at rest on Doppler and tissue Doppler imaging.

Registered date

2024

Year

04

Month

04

Day

Last modified on

2025

Year

08

Month

12

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000061718