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HFpEFPhase 2NCT06655480

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

A Phase 2 study testing [ARNI + SGLTi + AMR] and [SGLTi + previously taken RAAS blocker] in people with HFpEF and LVDD, run by National Medical Research Center for Cardiology, Ministry of Health of Russian Federation at 1 site in Russia.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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… Read more about this study

Who is it for?
Ages 40 to 80 years
Conditions the study is for
HFpEF, LVDD, Myocardial Fibrosis
What is being tested?
[ARNI + SGLTi + AMR] and [SGLTi + previously taken RAAS blocker]
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
1 siteRussia
Study dates
18 Mar 2025to 31 Dec 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 40 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
Show all 15Show fewer
  • 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

Who cannot join

  • 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;
Show all 26Show fewer
  • 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;
  • Glycated hemoglobin level > 9% or <6%

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Artem G Ovchinnikov, MD, PhD, DSc contact

+74954146612

artcardio@mail.ru

Russia1 site, 1 recruiting

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

    Moscow

    Artem G Ovchinnikov,, MD, PhD, DSc, +74954146612, artcardio@mail.ru

    Recruiting

Other trials in Russia

About this study

Official title: Effect on Clinical Status, Structural and Functional Cardiac Parameters and Myocardial Fibrosis of Triple Combination Therapy With a Sodium-glucose Cotransporter 2 Inhibitor, Angiotensin Receptor/Neprilysin Inhibitor and Mineralocorticoid Receptor Antagonist in Patients With Advanced HFpEF

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

Read the detailed description

HFpEF has a significant morbidity and mortality, and the therapeutic options for HFpEF are limited. According to the results of clinical HFpEF trials, SGLTis and MRA can improve prognosis (EMPEROR-preserved, DELIVER, FINEARTS-HF trials); and ARNI can reduce the risk of hospitalization due to exacerbation of heart failure (PARAGON-HF trial). There is also clinical and experimental evidence of anti-inflammatory and antifibrotic effects in SGLTi, MRA and ARNI. However, there are currently no randomized clinical trials evaluating the efficacy of the combination therapy with all these drugs in HFpEF. The investigators suppose that triple combination therapy with [ARNI + SGLTi + AMR] in HFpEF will have a pronounced, rapid and safe positive clinical and haemodynamic effect primarily through its effect on fibrosis and inflammation in patients with HFpEF.

Being tested
[ARNI + SGLTi + AMR], [SGLTi + previously taken RAAS blocker]
Keywords
HFpEF, HF, left ventricular hypertrophy, diastolic dysfunction, cardiac reserves, LV filling pressures, myocardial fibrosis
Medical subject headings
Hypertrophy, Left Ventricular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • [ARNI + SGLTi + AMR]Drug

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

  • [SGLTi + previously taken RAAS blocker]Drug

    Empagliflozin 10mg tablet, previously taken RAAS inhibitor

Study groups in NCT06655480
Study groupRoleWhat they receive
[ARNI + SGLTi + AMR]ExperimentalPatients will receive combination therapy with ARNI, gliflozin and AMR
Receives: Drug: [ARNI + SGLTi + AMR]
[SGLTi + previously taken RAAS blocker]Active comparatorPatients will receive combination therapy with gliflozin and previously taken RAAS blocker
Receives: Drug: [SGLTi + previously taken RAAS blocker]

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in myocardial extracellular volume (MRI)

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

    Measured: 52 weeks

  2. 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

    Measured: 52 weeks

  3. 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

    Measured: 52 weeks

  4. 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

    Measured: 52 weeks

  5. Change in left atrial volume index (LAVi)

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

    Measured: 52 weeks

Secondary outcomes (9)

  1. Change in left ventricular mass index (LVMi)

    Difference in LVMi assessed by MRI between 52 weeks after baseline and at baseline

    Measured: 52 weeks

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

    Difference in Minnesota Living with Heart Failure Questionnaire (MLHFQ, potential scoring range between 0 and 105; higher scores mean a worse outcome) score between 52 weeks after baseline and at baseline

    Measured: 52 weeks

  3. Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) score

    Difference in Kansas City Cardiomyopathy Questionnaire (KCCQ; a range of possible subscale scores is from 0 to 100, with 100 representing the least burden of symptoms. The total KCCQ score represents the mean of the three subscale scores) score between 52 weeks after baseline and at baseline

    Measured: 52 weeks

  4. Change in biomarkers of inflammation and fibrosis

    Difference in plasma levels of inflammatory and fibrosis biomarkers (hsCRP, GDF-15, PICP, galectin-3, MCP-1) between 52 weeks after baseline and at baseline

    Measured: 52 weeks

  5. Change in cardiac hemodynamic reserves - LV contractile

    Difference in cardiac hemodynamic reserves (LV contractile) during DST between 52 weeks after baseline and at baseline

    Measured: 52 weeks

  6. Change in cardiac hemodynamic reserves - LV diastolic

    Difference in cardiac hemodynamic reserves (LV diastolic) during DST between 52 weeks after baseline and at baseline

    Measured: 52 weeks

  7. Change in cardiac hemodynamic reserves - LA reservoir

    Difference in cardiac hemodynamic reserves (LA reservoir) during DST between 52 weeks after baseline and at baseline

    Measured: 52 weeks

  8. Change in cardiac hemodynamic reserves - cardiac chronotropic

    Difference in cardiac hemodynamic reserves (cardiac chronotropic) during DST between 52 weeks after baseline and at baseline

    Measured: 52 weeks

  9. Change in cardiac hemodynamic reserves - RV contractile

    Difference in cardiac hemodynamic reserves (RV contractile) during DST between 52 weeks after baseline and at baseline

    Measured: 52 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Oct 2024
  2. Study start18 Mar 2025
  3. Primary completion31 Dec 2027 (estimated)
  4. Study completion31 Dec 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
50 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06655480
Sponsor's protocol ID
124020200111-6
Status last verified
Apr 2026
First submitted
21 Oct 2024
Last updated
24 Apr 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Muhammad Daniyal S, Ajaz H, Riaz M, Murad Khatoon N, Aftab Z, Tauqir Gondal H, Gul I, Sarwar M, Batool F, Fahim SL, Noor A, Khalid A, Ashraf DA, Jabarkhil R. Combination therapy with mineralocorticoid receptor antagonists and SGLT2 inhibitors versus SGLT2 inhibitor monotherapy in chronic kidney disease: an updated meta-analysis of randomized controlled trials. BMC Nephrol. 2025 Dec 22;27(1):69. doi: 10.1186/s12882-025-04710-2.

    PubMed 41430169

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing [ARNI + SGLTi + AMR] and [SGLTi + previously taken RAAS blocker] in people with HFpEF and LVDD, run by National Medical Research Center for Cardiology, Ministry of Health of Russian Federation at 1 site in Russia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 24 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Artem G Ovchinnikov, MD, PhD, DSc (+74954146612, artcardio@mail.ru), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in myocardial extracellular volume (MRI) (time frame: 52 weeks). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06655480, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Apr 2026.

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