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

June 14, 2023 updated by: Clinical Hospital Heliodor Swiecicki of the Medical University of Karol Marcinkowski in Poznań

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
260

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Marta Kałużna-Oleksy, MD, PhD
  • Phone Number: 0048 502 896 932
  • Email: marta.kaluzna@wp.pl

Study Locations

  • Poland
      • Białystok, Poland, 15-276
        • Not yet recruiting
        • Medical University of Bialystok Clinical Hospital
        • Contact:
          • Agnieszka Tycińska, Prof. MD
        • Principal Investigator:
          • Agnieszka Tycińska, Prof. MD
      • Gdańsk, Poland, 80-952
        • Not yet recruiting
        • University Clinical Centre in Gdansk
        • Contact:
          • Marcin Gruchała, Prof. MD
        • Principal Investigator:
          • Marcin Gruchała, Prof. MD
      • Opole, Poland, 45-401
        • Not yet recruiting
        • University Clinical Hospital in Opole
        • Contact:
          • Marek Gierlotka, Prof. MD
        • Principal Investigator:
          • Marek Gierlotka, Prof. MD
      • Poznań, Poland, 61-848
        • Recruiting
        • University Hospital in Poznan
        • Contact:
        • Principal Investigator:
          • Ewa Straburzyńska-Migaj, Prof. MD
      • Zabrze, Poland, 41-800
        • Not yet recruiting
        • Specialist Hospital in Zabrze
        • Contact:
          • Ewa Nowalany-Kozielska, Prof. MD
        • Principal Investigator:
          • Ewa Nowalany-Kozielska, Prof. MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Sacubitril and valsartan combination
Patient receive: 1 bottle with Sacubitril/Valsartan tablets and 2nd bottle with placebo to enalapril.
Drug: 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
Drug: Placebo
placebo matching for 2.5 mg, 5 mg, 10 mg of enalapril
Active Comparator: Enalapril
Patient receive: 1 bottle with placebo to Sacubitril/Valsartan and 2nd bottle with enalapril.
Drug: Enalapril
level 1-2.5 mg twice a day, level 2-5 mg twice a day, level 3-10 mg twice a day
Drug: placebo
placebo matching for 24 / 26mg, 49 / 51mg, 97 / 103mg 2 of sacubitril/valsartan

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
mean pulmonary artery pressure
Time Frame: 0-13 month
change from baseline in mean pulmonary artery pressure (mPAP), measured invasively in Right Heart Catheterization (RHC)
0-13 month
pulmonary vascular resistance
Time Frame: 0-13 month
change from baseline in pulmonary vascular resistance (PVR), calculated from data measured invasively in Right Heart Catheterization (RHC)
0-13 month

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
pulmonary wedge pressure
Time Frame: 0 -13 month
change from baseline in pulmonary wedge pressure (PWP), measured invasively in Right Heart Catheterization (RHC)
0 -13 month
diastolic pressure gradient
Time Frame: 0-13 month
change from baseline in the diastolic pressure gradient (DPG; where DPG = diastolic mPAP -mean PWP)
0-13 month
6-minute walk test
Time Frame: 0-13 month
change in the 6-minute walk test (6MWT) - analysis of changes from the baseline
0-13 month
spiroergometric test (CPET, Cardio-Pulmonary Exercise Test)
Time Frame: 0-13 month
evaluation of the parameters of the spiroergometric test - analysis of changes in relation to the baseline
0-13 month
echocardiographic parameters
Time Frame: 0-13 month
assessment of echocardiographic parameters - analysis of changes in echocardiographic parameters assessed in transthoracic echocardiographic examination (TTE)
0-13 month
composite endpoint of MACCEs (major adverse cardiac and cerebrovascular events)
Time Frame: 0-13 month
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)
0-13 month
hospitalization or an unplanned visit to the Emergency Department
Time Frame: 0-13 month
hospitalization or an unplanned visit to the Emergency Department or an unplanned outpatient visit related to HF
0-13 month
unplanned intravenous administration of diuretics and/or an unplanned hospitalization
Time Frame: 0-13 month
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
0-13 month
quality of life measurements - Short Form 36 Health Survey (SF-36 questionnaire)
Time Frame: 0-13 month
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.
0-13 month
quality of life measurements - Kansas City Cardiomyopathy Questionnaire (KCCQ)
Time Frame: 0-13 month
assessment of quality of life - KCCQ, the minimum and maximum values: 0-100, higher scores mean higher quality of life.
0-13 month
quality of life measurements - EuroQol-5 Dimensions-3 Level (EQ-5D-3L) questionnaire
Time Frame: 0-13 month
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.
0-13 month
quality of life measurements - The World Health Organization Quality of Life (WHOQOL)
Time Frame: 0-13 month
assessment of quality of life - WHOQOL - change from the baseline, the minimum and maximum values: 0-100, higher scores mean higher quality of life.
0-13 month
the New York Heart Association functional classes
Time Frame: 0-13 month
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.
0-13 month
the World Health Organization functional classes
Time Frame: 0-13 month
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.
0-13 month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Clinical Hospital Heliodor Swiecicki of the Medical University of Karol Marcinkowski in Poznań

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Medical University of Silesia
Medical University of Gdansk
Medical University of Bialystok
Medical Research Agency, Poland
University of Opole

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Ewa Straburzyńska-Migaj, Prof. MD, University Hospital in Poznan

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 13, 2022

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 1, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 26, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 2, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 4, 2022

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 16, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 14, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2019/ABM/01/00078

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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