Effects of Sacubitril/Valsartan on Heart Failure with Pulmonary Hypertension

Pulmonary REsistance Modification Under Treatment With Sacubitril/valsartaN in paTients With Heart Failure With Reduced Ejection Fraction - PRESENT HF Study

This study is testing if a heart medication called sacubitril/valsartan can help people with heart failure and high blood pressure in their lungs feel better and improve their heart function.

Quick facts

• Phase: PHASE4
• Study type: Interventional
• Enrollment: 260 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Clinical Hospital Heliodor Swiecicki of the Medical University of Karol Marcinkowski in Poznań (other)
• Locations: 5 sites (Białystok and 4 other locations)
• Trial ID: NCT05487261 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the impact of sacubitril/valsartan on pulmonary artery pressure and pulmonary circulation resistance in patients with heart failure with reduced ejection fraction (HFrEF) and post-capillary pulmonary hypertension. It is a multicenter, randomized, double-blind, comparator-controlled study where eligible patients are assigned to receive either the treatment or a comparator. The study aims to demonstrate that sacubitril/valsartan can improve hemodynamic parameters and potentially enhance patient prognosis over a 13-month observation period.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with HFrEF and post-capillary pulmonary hypertension.

Not a fit: Patients with heart failure not accompanied by pulmonary hypertension or those with contraindications to sacubitril/valsartan may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve the management and outcomes for patients with heart failure and pulmonary hypertension.

How similar studies have performed: Other studies have shown promising results with sacubitril/valsartan in heart failure management, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. Age ≥18 years of age who are able to complete and sign the informed consent form.
2. HF patients in NYHA functional class II-IV with a reduced left ventricular ejection fraction (LVEF) ≤40% -(HFrEF) (confirmed by an examination such as echocardiography or cardiac magnetic resonance within the last 6 months) in whom right heart catheterization (RHC) reveals post-capillary or mixed pulmonary hypertension (defined on the basis of the 2015 ESC (European Society of Cardiology) guidelines: mean pulmonary artery pressure (PAPm) ≥25 mmHg and pulmonary capillary wedge pressure (PCWP)\>15mmHg) were found, both of the isolated extracapillary PH (Ipc-PH) (defined on the basis of the 2015 ESC guidelines: DPG \< 7 mm Hg and / or PVR ≤ 3 WU) as well as complex extra-and pre-capillary PH (Cpc-PH) (defined on the basis of the 2015 ESC guidelines: DPG ≥ 7 mm Hg and / or PVR\> 3 WU).
3. Stable patients haemodynamics, which is defined as no change in diuretic use for at least 4 weeks prior to study entry.
4. HF during optimal treatment with ACE-I (angiotensin converting enzyme) /ARB (angiotensin receptor blocker), beta blocker, MRA (Mineralocorticoid Receptor Antagonists), SGLT2-I except in cases where the above-mentioned treatment was contraindicated or not tolerated.
5. Understanding and acceptance of the research assumptions and methods and signing the informed consent by the patient.

Exclusion Criteria:

1. Current treatment with S/V.
2. Cardiogenic shock.
3. Current treatment with sildenafil.
4. Patients ineligible or contraindicated for treatment with sacubitril-valsartan.
5. Patients with a history of angioedema.
6. Patients who have had a heart transplant or have had a circulatory support device.
7. Patient on the urgent list for heart transplant.
8. Isolated right HF secondary to lung disease.
9. Documented untreated significant ventricular arrhythmia with syncope within the previous 3 months.
10. Symptomatic bradycardia or second or third degree atrioventricular block not protected by a pacemaker.
11. Factors that prevent RHC testing (e.g. very serious condition of the patient that makes it impossible to lie down, cardiogenic shock, allergy to contrast agents, etc.).
12. Pregnant or lactating women.
13. Women of childbearing age, defined as the physiological possibility of becoming pregnant, unless using two methods of contraception.
14. Acute coronary syndrome, including myocardial infarction (STEMI, NSTEMI), a condition with carotid revascularization or major cardiovascular surgery in the last 30 days.
15. Stroke or transient cerebral ischemia (TIA) within the last 3 months.
16. Previous CRT (Cardiac Resynchronization Therapy) implantation in the last 3 months or planning for CRT implantation.
17. Life expectancy \<6 months.
18. Severe renal failure, eGFR (epidermal growth factor receptor) \<30 ml / min / 1.73 m2(calculated according to the MDRD formula).
19. Serum potassium\> 5.2 mEq/L.
20. Liver failure or elevated liver transaminases (total bilirubin\> 3 mg / dL and/or ALT (Aspartate transaminase) and/or AST (Aspartate Aminotransferase) ≥3x ULN).
21. A major surgery planned within 6 months of randomization.
22. Planned coronary angioplasty or pacemaker / ICD (implantable cardioverter defibrillator) / CRT implantation within the next 6 months.
23. Severe primary valve disease (NOT secondary mitral regurgitation) or obstructive hypertrophic cardiomyopathy.
24. The presence of a malignant neoplasm of any organ system, ie clinical signs or no stable remission for at least 3 years after the end of the last treatment, with the exception of non-invasive basal cell carcinoma, squamous cell carcinoma of the skin or cervical epithelial dysplasia.
25. Diseases that significantly reduce physical performance:

    1. severe COPD (chronic obstructive pulmonary disease) putting off oxygen therapy,
    2. severe asthma,
    3. morbid obesity (BMI\> 40 kg / m2),
    4. significant lower limb atherosclerosis with intense intermittent claudication.
26. Uncontrolled hypertension (SBP\> 170 mmHg and / or DBP\> 100 mmHg).
27. Symptomatic hypotension (SPB \<90 mmHg)
28. Any situation that may make it impossible to perform the research in accordance with the protocol or express written consent in the opinion of the researcher, including abuse of alcohol, drugs or other psychoactive substances.
29. Participation in a study with a device or medicinal product within 3 months prior to randomization or 5 half-lives, whichever is longer, prior to the screening visit.

Where this trial is running

Białystok and 4 other locations

• Medical University of Bialystok Clinical Hospital — Białystok, Poland (NOT_YET_RECRUITING)
• University Clinical Centre in Gdańsk — Gdańsk, Poland (NOT_YET_RECRUITING)
• University Clinical Hospital in Opole — Opole, Poland (NOT_YET_RECRUITING)
• University Hospital in Poznan — Poznań, Poland (RECRUITING)
• Specialist Hospital in Zabrze — Zabrze, Poland (NOT_YET_RECRUITING)

Study contacts

• Principal investigator: Ewa Straburzyńska-Migaj, Prof. MD — University Hospital in Poznan
• Study coordinator: Marta Kałużna-Oleksy, MD, PhD

Conditions: Heart Failure