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.
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 \[1months active up titration phase + 12 months follow up\].
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
260
level 1-24 / 26mg 2 times a day, level 2-49 / 51mg 2 times a day, level 3-97 / 103mg 2 times aday
level 1-2.5 mg twice a day, level 2-5 mg twice a day, level 3-10 mg twice a day
placebo matching for 24 / 26mg, 49 / 51mg, 97 / 103mg 2 of sacubitril/valsartan
placebo matching for 2.5 mg, 5 mg, 10 mg of enalapril
Medical University of Bialystok Clinical Hospital
Bialystok, Poland
NOT_YET_RECRUITINGUniversity Clinical Centre in Gdańsk
Gdansk, Poland
NOT_YET_RECRUITINGUniversity Clinical Hospital in Opole
Opole, Poland
NOT_YET_RECRUITINGUniversity Hospital in Poznan
Poznan, Poland
RECRUITINGSpecialist Hospital in Zabrze
Zabrze, Poland
NOT_YET_RECRUITINGmean pulmonary artery pressure
change from baseline in mean pulmonary artery pressure (mPAP), measured invasively in Right Heart Catheterization (RHC)
Time frame: 0-13 month
pulmonary vascular resistance
change from baseline in pulmonary vascular resistance (PVR), calculated from data measured invasively in Right Heart Catheterization (RHC)
Time frame: 0-13 month
pulmonary wedge pressure
change from baseline in pulmonary wedge pressure (PWP), measured invasively in Right Heart Catheterization (RHC)
Time frame: 0 -13 month
diastolic pressure gradient
change from baseline in the diastolic pressure gradient (DPG; where DPG = diastolic mPAP -mean PWP)
Time frame: 0-13 month
6-minute walk test
change in the 6-minute walk test (6MWT) - analysis of changes from the baseline
Time frame: 0-13 month
spiroergometric test (CPET, Cardio-Pulmonary Exercise Test)
evaluation of the parameters of the spiroergometric test - analysis of changes in relation to the baseline
Time frame: 0-13 month
echocardiographic parameters
assessment of echocardiographic parameters - analysis of changes in echocardiographic parameters assessed in transthoracic echocardiographic examination (TTE)
Time frame: 0-13 month
composite endpoint of MACCEs (major adverse cardiac and cerebrovascular events)
The incidence of the composite endpoint of MACCEs such as death from all causes, cardiac death, hospitalization due to worsening/ decompensation of heart failure (HF), stroke/ transient ischemic attack (TIA), acute coronary syndrome (ACS), the need for a heart transplant (HT), the need for a left ventricular assist device (LVAD) or biventricular(BVAD)
Time frame: 0-13 month
hospitalization or an unplanned visit to the Emergency Department
hospitalization or an unplanned visit to the Emergency Department or an unplanned outpatient visit related to HF
Time frame: 0-13 month
unplanned intravenous administration of diuretics and/or an unplanned hospitalization
the need for unplanned intravenous administration of diuretics and/or an unplanned hospitalization, outpatient visit due to the need to administer intravenous diuretics or requiring an increase in the dose of diuretics \>50% from baseline
Time frame: 0-13 month
quality of life measurements - Short Form 36 Health Survey (SF-36 questionnaire)
assessment of quality of life - SF-36 questionnaire - change from the baseline, the minimum and maximum values: 0-100, higher scores mean a less disability.
Time frame: 0-13 month
quality of life measurements - Kansas City Cardiomyopathy Questionnaire (KCCQ)
assessment of quality of life - KCCQ, the minimum and maximum values: 0-100, higher scores mean higher quality of life.
Time frame: 0-13 month
quality of life measurements - EuroQol-5 Dimensions-3 Level (EQ-5D-3L) questionnaire
assessment of quality of life - EQ-5D-3L questionnaire - change from the baseline, the minimum and maximum values: 0-100, higher scores mean higher quality of life.
Time frame: 0-13 month
quality of life measurements - The World Health Organization Quality of Life (WHOQOL)
assessment of quality of life - WHOQOL - change from the baseline, the minimum and maximum values: 0-100, higher scores mean higher quality of life.
Time frame: 0-13 month
the New York Heart Association functional classes
assessment of the New York Heart Association (NYHA) functional classes - change from the baseline, the minimum and maximum values: 1-4, higher scores mean a worse outcome.
Time frame: 0-13 month
the World Health Organization functional classes
assessment of the World Health Organization (WHO) functional classes - change from the baseline, the minimum and maximum values: 1-4, higher scores mean a worse outcome.
Time frame: 0-13 month
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