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

Recruiting now · Phase 2

Conditions studied: HFpEF, LVDD, Myocardial Fibrosis

In brief

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

Key facts

Study ID: NCT06655480
Run by: National Medical Research Center for Cardiology, Ministry of Health of Russian Federation
People needed: 50
Starts: 2025-03-18
Expected to finish: 2027-12-31
Last updated by the study team: 2026-04-24

Who can join

Age: 40 and older, up to 80. Sex: any. Healthy volunteers: not accepted.

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;
Continuous (>90 days) treatment with ARNI, SGLTi and/or AMR within 12 months prior to screening. The last administration of these drugs must be at least 30 days prior to randomization. Treatment with these drugs should not be interrupted for the purpose of inclusion in the study.
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);
Impaired liver function (serum levels of alanine aminotransferase, aspartate aminotransferase, or alkaline phosphatase above 3 × upper limit of normal);
Addison's disease;
Known hypersensitivity to medications used the in the study;
Non-cardiac conditions that complicate/exclude participation in the study;
Diseases associated with isolated LV insufficiency (idiopathic pulmonary hypertension, chronic thromboembolic pulmonary hypertension, etc.);
Serum/plasma potassium >5.0 mmol/L at screening or randomization or a history of hyperkalemia or acute renal failure during AMR treatment for >7 consecutive days leading to discontinuation of AMR treatment.
For patients with diabetes mellitus:
Type 1 diabetes mellitus;
Presence of more than 4 episodes of moderate hypoglycemia within the past month or at least one episode of severe hypoglycemia within the past year;

Where it is running

National Medical Research Center for Cardiology, Ministry of Health of Russian Federation — Moscow, Russia (enrolling)

Full record on ClinicalTrials.gov

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