Triple Combination Therapy (ARNI, SGLT2i, MRA) in Advanced HFpEF

NCT06655480 | Recruiting Phase 2

• 1 other identifier: 124020200111-6
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with advanced heart failure with preserved ejection fraction (HFpEF) will be randomly assigned in open-label multicenter study to receive triple combination therapy with \[angiotensin receptor/neprilysin inhibitor \[ARNI\] + sodium-glucose cotransporter 2 inhibitor \[SGLTi\] + mineralocorticoid receptor antagonist \[MRA\]) or with individualized medical therapy \[SGLTi + renin-angiotensin system inhibitor \[RASi\] \[angiotensin receptor blocker \[ARB\] or angiotensin-converting enzyme inhibitor \[ACE-I\]), and will be treated for 52 weeks

Conditions

HFpEF; LVDD; Myocardial Fibrosis

Keywords

HFpEF; HF; left ventricular hypertrophy; diastolic dysfunction; cardiac reserves; LV filling pressures; myocardial fibrosis

Outcome Measures

Primary Outcomes (5)

• Change in myocardial extracellular volume (MRI)

  Difference in myocardial extracellular volume assessed by MRI data between 52 weeks after baseline and at baseline

  52 weeks

• Change in 6-minute walking distance (6MWD)

  Difference in distance walked during 6-minute walking test (6MWT) between 52 weeks after baseline and at baseline

  52 weeks

• Change in N-terminal pro b-type natriuretic peptide (NT-proBNP)

  Difference in NT-proBNP plasma levels between 52 weeks after baseline and at baseline

  52 weeks

• Change in average E/e' ratio and tricuspid regurgitation velocity

  Difference in E/e' ratio and tricuspid regurgitation velocity assessed by echocardiography both at rest and at peak exercise during diastolic stress test (DST) between 52 weeks after baseline and at baseline

  52 weeks

• Change in left atrial volume index (LAVi)

  Difference in LAVi assessed by echocardiography between 52 weeks after baseline and at baseline

  52 weeks

Secondary Outcomes (9)

• Change in left ventricular mass index (LVMi)

  52 weeks

• Change in Minnesota Living with Heart Failure Questionnaire (MLHFQ) score

  52 weeks

• Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) score

  52 weeks

• Change in biomarkers of inflammation and fibrosis

  52 weeks

• Change in cardiac hemodynamic reserves - LV contractile

  52 weeks

Study Arms (2)

[ARNI + SGLTi + AMR]

EXPERIMENTAL

Patients will receive combination therapy with ARNI, gliflozin and AMR

Drug: [ARNI + SGLTi + AMR]

[SGLTi + previously taken RAAS blocker]

ACTIVE COMPARATOR

Patients will receive combination therapy with gliflozin and previously taken RAAS blocker

Drug: [SGLTi + previously taken RAAS blocker]

Interventions

[ARNI + SGLTi + AMR] DRUG

Empagliflozin 10mg tablet, Valsartan+Sacubitril 100-200-400 mg tablet, Finerenone 20-40 mg tablet

[ARNI + SGLTi + AMR]

[SGLTi + previously taken RAAS blocker] DRUG

Empagliflozin 10mg tablet, previously taken RAAS inhibitor

[SGLTi + previously taken RAAS blocker]

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed and data informed consent;
• Symptoms and signs of HF;
• LV ejection fraction \> 50%;
• NT-proBNP \> 300 pg/mL (for patients with atrial fibrillation NT-proBNP \> 900 pg/mL)
• LV diastolic dysfunction II-III grade OR
• LV diastolic dysfunction I grade and at least 2 out of 4:
• Е/е' \> 14
• LAVi \> 34 ml/m2 (for those with persistent atrial fibrillation \> 40 ml/m2)
• PASP \> 35 mm Hg or TR velocity \> 2.8 m/sec
• LV mass index \> 95 g/m2 for women / \> 115 g/m2 for men or LV interventricular septum or posterior wall thickness ≥ 1.1 sm OR
• Chronic atrial fibrillation and at least 3 out of 4:
• Е/е' \> 11
• E-wave velocity \> 100 sm/s
• TR velocity \> 2.8 sm/s
• DT ≤ 160 ms

You may not qualify if:

• Evidence of myocardial ischemia during stress echocardiography;
• Significant lesions of main coronary arteries;
• Atrial fibrillation with resting HR \> 110 beats/min;
• Coronary bypass surgery, stroke or TIA within the last 3 months of screening;
• Myocardial infarction or myocardial revascularization within the last 3 months of screening;
• Systolic blood pressure \< 90 mmHg or ≥ 180 mmHg at screening or randomization;
• Genetic forms of HFpEF (HCM, amyloidosis, Fabry disease, glycogen storage diseases etc.);
• Peripartum cardiomyopathy, chemotherapy-induced cardiomyopathy, viral myocarditis, isolated right-sided HF without left-sided structural disease, constrictive pericarditis, significant pericardial effusion;
• Dyspnea due to non-cardiac causes such as pulmonary disease, anemia, severe obesity, primary valvular, or myocardial diseases;
• Significant lung disease (severe lung disease requiring home oxygen or chronic oral steroid therapy);
• Primary pulmonary artery hypertension;
• Significant left sided structural valve disease;
• Anemia (Hb \< 100 g/L);
• Obesity (body mass index \> 50 kg/m2);
• Impaired renal function, defined as estimated glomerular filtration rate (eGFR) \<30 mL/min/1.73 m2 (CKD-EPI);

Sponsors & Collaborators

• National Medical Research Center for Cardiology, Ministry of Health of Russian Federation: lead
• Lomonosov Moscow State University Medical Center: collaborator

Study Sites (1)

National Medical Research Center for Cardiology, Ministry of Health of Russian Federation

Moscow, Russia

RECRUITING

MeSH Terms

Conditions

Hypertrophy, Left Ventricular

Condition Hierarchy (Ancestors)

Cardiomegaly; Heart Diseases; Cardiovascular Diseases; Hypertrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Artem G Ovchinnikov, MD, PhD, DSc

CONTACT

+74954146612; artcardio@mail.ru

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2024
• First Posted: October 23, 2024
• Study Start: March 18, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: April 24, 2026

Record last verified: 2026-04

Locations

RU (1)