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

NCT05487261 | Unknown Phase 4

• 1 other identifier: 2019/ABM/01/00078
• Study Type: interventional
• Target: 260
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Heart Failure

Outcome Measures

Primary Outcomes (2)

• mean pulmonary artery pressure

  change from baseline in mean pulmonary artery pressure (mPAP), measured invasively in Right Heart Catheterization (RHC)

  0-13 month

• pulmonary vascular resistance

  change from baseline in pulmonary vascular resistance (PVR), calculated from data measured invasively in Right Heart Catheterization (RHC)

  0-13 month

Secondary Outcomes (14)

• pulmonary wedge pressure

  0 -13 month

• diastolic pressure gradient

  0-13 month

• 6-minute walk test

  0-13 month

• spiroergometric test (CPET, Cardio-Pulmonary Exercise Test)

  0-13 month

• echocardiographic parameters

  0-13 month

Study Arms (2)

Sacubitril and valsartan combination

EXPERIMENTAL

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

Drug: Sacubitril-valsartan; Drug: Placebo

Enalapril

ACTIVE COMPARATOR

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

Drug: Enalapril; Drug: placebo

Interventions

Sacubitril-valsartan DRUG

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

Sacubitril and valsartan combination

Enalapril DRUG

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

Enalapril

Placebo DRUG

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

Enalapril

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years of age who are able to complete and sign the informed consent form.
• 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).
• Stable patients haemodynamics, which is defined as no change in diuretic use for at least 4 weeks prior to study entry.
• 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.
• Understanding and acceptance of the research assumptions and methods and signing the informed consent by the patient.

You may not qualify if:

• Current treatment with S/V.
• Cardiogenic shock.
• Current treatment with sildenafil.
• Patients ineligible or contraindicated for treatment with sacubitril-valsartan.
• Patients with a history of angioedema.
• Patients who have had a heart transplant or have had a circulatory support device.
• Patient on the urgent list for heart transplant.
• Isolated right HF secondary to lung disease.
• Documented untreated significant ventricular arrhythmia with syncope within the previous 3 months.
• Symptomatic bradycardia or second or third degree atrioventricular block not protected by a pacemaker.
• 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.).
• Pregnant or lactating women.
• Women of childbearing age, defined as the physiological possibility of becoming pregnant, unless using two methods of contraception.
• Acute coronary syndrome, including myocardial infarction (STEMI, NSTEMI), a condition with carotid revascularization or major cardiovascular surgery in the last 30 days.
• Stroke or transient cerebral ischemia (TIA) within the last 3 months.

Sponsors & Collaborators

• Clinical Hospital Heliodor Swiecicki of the Medical University of Karol Marcinkowski in Poznań: lead
• Medical Research Agency, Poland: collaborator
• Medical University of Bialystok: collaborator
• University of Opole: collaborator
• Medical University of Gdansk: collaborator
• Medical University of Silesia: collaborator

Study Sites (5)

Medical University of Bialystok Clinical Hospital

Bialystok, 15-276, Poland

NOT YET RECRUITING

University Clinical Centre in Gdańsk

Gdansk, 80-952, Poland

NOT YET RECRUITING

University Clinical Hospital in Opole

Opole, 45-401, Poland

NOT YET RECRUITING

University Hospital in Poznan

Poznan, 61-848, Poland

RECRUITING

Specialist Hospital in Zabrze

Zabrze, 41-800, Poland

NOT YET RECRUITING

MeSH Terms

Conditions

Heart Failure

Interventions

sacubitril and valsartan sodium hydrate drug combination; Enalapril

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Dipeptides; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Ewa Straburzyńska-Migaj, Prof. MD

  University Hospital in Poznan

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marta Kałużna-Oleksy, MD, PhD

CONTACT

502 896 932; marta.kaluzna@wp.pl

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2022
• First Posted: August 4, 2022
• Study Start: December 13, 2022
• Primary Completion: February 1, 2025
• Study Completion: November 1, 2025
• Last Updated: June 18, 2023

Record last verified: 2023-06

Locations

PL (5)