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

NCT ID: NCT05487261

Last Updated: 2023-06-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

260 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-12-13

Study Completion Date

2025-11-30

Brief Summary

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MAIN OBJECTIVE. Demonstration that use of sacubitril/valsartan influences parameters of right heart catheterization, including pulmonary artery pressure, and provokes changes in pulmonary circulation resistance in patients with heart failure with reduced left ventricular ejection fraction (HFrEF) and post-capillary pulmonary hypertension (PH): both isolated post-capillary (Ipc-PH) and combined post- and pre-capillary (Cpc-PH), which we predict could improve prognosis in this group of patients.

RESEARCH HYPOTHESIS. Sacubitril/valsartan used in patients with HFrEF accompanied by pulmonary hypertension due to HFrEF will reduce pulmonary artery pressure, pulmonary vascular resistance, and the incidence of secondary end-points as listed in the protocol.

STUDY OUTLINE. PRESENT-HF will show the effects of sacubitril/valsartan on pulmonary circulation pressure in patients with HFrEF and post-capillary pulmonary hypertension (PH): both isolated post-capillary (Ipc-PH) and combined post- and pre-capillary (Cpc-PH), which is expected to improve prognosis.

Detailed Description

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Non commercial, multicentre, randomised, double-blind, comparator-controlled clinical trial. Eligible patients were randomly assigned (1:1) using a secure, central, interactive, web-based response system, to intervention or comparator arm. Time of observation 13 months \[1months active up titration phase + 12 months follow up\].

Conditions

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Heart Failure

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Sacubitril and valsartan combination

Patient receive: 1 bottle with Sacubitril/Valsartan tablets and 2nd bottle with placebo to enalapril.

Group Type EXPERIMENTAL

Sacubitril-valsartan

Intervention Type DRUG

level 1-24 / 26mg 2 times a day, level 2-49 / 51mg 2 times a day, level 3-97 / 103mg 2 times aday

Placebo

Intervention Type DRUG

placebo matching for 2.5 mg, 5 mg, 10 mg of enalapril

Enalapril

Patient receive: 1 bottle with placebo to Sacubitril/Valsartan and 2nd bottle with enalapril.

Group Type ACTIVE_COMPARATOR

Enalapril

Intervention Type DRUG

level 1-2.5 mg twice a day, level 2-5 mg twice a day, level 3-10 mg twice a day

placebo

Intervention Type DRUG

placebo matching for 24 / 26mg, 49 / 51mg, 97 / 103mg 2 of sacubitril/valsartan

Interventions

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Sacubitril-valsartan

level 1-24 / 26mg 2 times a day, level 2-49 / 51mg 2 times a day, level 3-97 / 103mg 2 times aday

Intervention Type DRUG

Enalapril

level 1-2.5 mg twice a day, level 2-5 mg twice a day, level 3-10 mg twice a day

Intervention Type DRUG

placebo

placebo matching for 24 / 26mg, 49 / 51mg, 97 / 103mg 2 of sacubitril/valsartan

Intervention Type DRUG

Placebo

placebo matching for 2.5 mg, 5 mg, 10 mg of enalapril

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Medical Research Agency, Poland

OTHER_GOV

Sponsor Role collaborator

Medical University of Bialystok

OTHER

Sponsor Role collaborator

University of Opole

OTHER

Sponsor Role collaborator

Medical University of Gdansk

OTHER

Sponsor Role collaborator

Medical University of Silesia

OTHER

Sponsor Role collaborator

Clinical Hospital Heliodor Swiecicki of the Medical University of Karol Marcinkowski in Poznań

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ewa Straburzyńska-Migaj, Prof. MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital in Poznan

Locations

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Medical University of Bialystok Clinical Hospital

Bialystok, , Poland

Site Status NOT_YET_RECRUITING

University Clinical Centre in Gdańsk

Gdansk, , Poland

Site Status NOT_YET_RECRUITING

University Clinical Hospital in Opole

Opole, , Poland

Site Status NOT_YET_RECRUITING

University Hospital in Poznan

Poznan, , Poland

Site Status RECRUITING

Specialist Hospital in Zabrze

Zabrze, , Poland

Site Status NOT_YET_RECRUITING

Countries

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Poland

Central Contacts

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Marta Kałużna-Oleksy, MD, PhD

Role: CONTACT

502 896 932 ext. 0048

Facility Contacts

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Agnieszka Tycińska, Prof. MD

Role: primary

Marcin Gruchała, Prof. MD

Role: primary

Marek Gierlotka, Prof. MD

Role: primary

Ewa Straburzyńska-Migaj, Prof. MD

Role: primary

Ewa Nowalany-Kozielska, Prof. MD

Role: primary

Other Identifiers

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2019/ABM/01/00078

Identifier Type: -

Identifier Source: org_study_id

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