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Heart Failure, Left SidedNCT04397302

Role of Sacubitril/Valsartan in the Improvement of Heart Failure With Reduced Ejection Fraction

An observational study of Heart Failure, Left Sided and Left Ventricular Dysfunction, run by Italian Society of Cardiology at 1 site in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This prospective study evaluates the mechanisms of benefit of sacubitril/valsartan in a population of outpatients with heart failure with reduced ejection fraction, to investigate the relationship between the effects on left ventricular ejection fraction and volumes and noninvasively hemodynamic echo-derived… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Role of Sacubitril/Valsartan in Hemodynamic and Echocardiographic Improvement of Heart Failure With Reduced Ejection Fraction
How many people
652 participants
Where
1 siteItaly
Study dates
13 Jan 2019to 16 Mar 2020
How long will I take part?
376 Days
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • Adult, Older adult

Study population: The participants were recruited from a population of ambulatory patients with heart failure and reduced LV ejection fraction, being treated by Units of Cardiology in 12 Italian University hospitals.

Who may be able to join

  • Ambulatory patients on stable optimal medical therapy
  • History of HF and LVEF ≤ 40%
  • II-III NYHA class

Who cannot join

  • History of congenital heart disease
  • Severe valvular disease or valvular surgery
  • Recent acute coronary syndromes or stroke
  • Poor acoustic windows or missing data.
  • Death or uncompleted follow-up evaluation
  • Cardiac surgery interventions
  • Cardiac resynchronization therapy
  • Coronary or mitral interventions

Trial locations and contacts

1 site in 1 country.

Italy1 site
  • Frank Lloyd Dini

    Pisa, 56124

Other trials in Italy

About this study

Official title: Reverse Remodeling is Associated With Hemodynamic Improvement and Stabilization in Outpatients With Heart Failure With Reduced Ejection Fraction Treated With Sacubitril/Valsartan: an Echocardiographic Study

This prospective study evaluates the mechanisms of benefit of sacubitril/valsartan in a population of outpatients with heart failure with reduced ejection fraction, to investigate the relationship between the effects on left ventricular ejection fraction and volumes and noninvasively hemodynamic echo-derived parameters, as cardiac output and left ventricular filling pressure.

Read the detailed description

Therapeutic interventions were made according to a titration protocol in stable optimal medical therapy. Therapy with sacubitril/valsartan was introduced after a 48-hour wash-out of an ACE inhibitor or after a 24-hour wash-out of an angiotensin receptor antagonist. Doses of sacubitril/valsartan were optimized to individual tolerability.

Echocardiography was performed at baseline and after 12 months. LV end-diastolic and end-systolic volumes were calculated according to the biplane Simpson's method according to the recommendations of the American Society of Echocardiography and European Association of Cardiovascular Imaging. Doppler examinations included assessment of early diastolic filling velocity and early diastolic mitral annular velocity, an averaged E/e' ≥ 13 was considered a surrogate marker of increased filling pressure.

The LV stroke volume was calculated as the product of the LV outflow tract area and the time-velocity integral of the aortic flow velocity or was evaluated as the difference between LVEDV and LVESV. The LVSV index was estimated as LVSV divided by body surface area. Cardiac output (CO) was measured as stroke volume times heart rate, and the cardiac index was estimated by dividing CO by body surface area.

Patients who presented reverse remodeling were considered those exhibiting a ≥ 10% increase in ejection fraction and ≥15% reduction in end-systolic volume compared to baseline.

The accuracy of the sources data was verified by using in-hospital medical records, computerized or paper, by checking data from ultrasound images, laboratory reports or ambulatory cardiological tests.

Detailed information on patients' medical history, including medications and loop diuretic doses, was recorded for each patient. Patients' functional status was determined according to the classification of the New York Heart Association. Creatinine, B-type natriuretic peptide and amino-terminal pro-type B-natriuretic peptide levels were measured using standard laboratory methods. The estimated glomerular filtration rate was calculated by the Modification of Diet in Renal Disease formula.

Patients were removed from therapy with sacubitril/valsartan or assessment for non-adherence to treatment or persistent drug-related adverse event with his/her willingness to discontinue treatment.

Continuous measures were expressed as the mean value ± SD or median and interquartile range (IRQ) for normally and non-normally distributed variables, respectively. Continuous data were compared using paired and independent samples Student t-test or ANOVA when appropriate. Categorical variables were presented as percentages and were compared using Chi-square or McNemar test. Mann-Whitney, Kruskal-Wallis and Wilcoxon tests were used to analyze non-normally distributed variables. All differences were considered significant at the p = 0.05 level. Data were analyzed with SPSS version 23.0 (IBM Corp., Armonk, NY).

Being tested
Role of Sacubitril/Valsartan in Hemodynamic and Echocardiographic Improvement of Heart Failure With Reduced Ejection Fraction
Keywords
Angiotensin-receptor neprilysin-inhibitor, Heart failure with reduced ejection fraction, Left ventricular filling pressure, Left ventricular reverse remodeling
Medical subject headings
Heart Failure, Ventricular Dysfunction, Left, Ventricular Remodeling

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Role of Sacubitril/Valsartan in Hemodynamic and Echocardiographic Improvement of Heart Failure With Reduced Ejection FractionDiagnostic test

    Reverse Remodeling is Associated With Hemodynamic Improvement and Stabilization in Outpatients With Heart Failure With Reduced Ejection Fraction Treated With Sacubitril/Valsartan: an Echocardiographic Study

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change from baseline in Cardiac Output after 12 months of treatment

    Cardiac Output (in L/min) is a variable measured by echocardiography as the product of LV stroke volume (in mL/beat) and heart rate (in bpm).

    Measured: March, 16 th 2019 - March,16th 2020

Secondary outcomes (1)
  1. Change from baseline in Left Ventricular Filling Pressure after 12 months of treatment

    Left ventricular filling pressure is calculated by Doppler Echocardiography as the ratio of early diastolic filling velocity (E wave, m/s) and early diastolic mitral annular velocity (e', m/s). The increase of this ratio is indicative of higher LV filling pressure.

    Measured: March, 16th 2019 - March,16th 2020

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 May 2020
  2. Study start13 Jan 2019
  3. Primary completion16 Mar 2020
  4. Study completion16 Mar 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Case only
Time perspective
Prospective
Enrolment
652 participants (actual)
Target duration
376 Days
IDs, dates and publications
ClinicalTrials.gov ID
NCT04397302
Sponsor's protocol ID
20190015213
Status last verified
May 2020
First submitted
4 May 2020
Last updated
28 May 2020
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided: It is not yet known if there will be a plan to make IPD available.

Publications

  • Metra M, Teerlink JR. Heart failure. Lancet. 2017 Oct 28;390(10106):1981-1995. doi: 10.1016/S0140-6736(17)31071-1. Epub 2017 Apr 28.

    PubMed 28460827
  • Januzzi JL Jr, Prescott MF, Butler J, Felker GM, Maisel AS, McCague K, Camacho A, Pina IL, Rocha RA, Shah AM, Williamson KM, Solomon SD; PROVE-HF Investigators. Association of Change in N-Terminal Pro-B-Type Natriuretic Peptide Following Initiation of Sacubitril-Valsartan Treatment With Cardiac Structure and Function in Patients With Heart Failure With Reduced Ejection Fraction. JAMA. 2019 Sep 17;322(11):1085-1095. doi: 10.1001/jama.2019.12821.

    PubMed 31475295
  • Mielniczuk LM, Tsang SW, Desai AS, Nohria A, Lewis EF, Fang JC, Baughman KL, Stevenson LW, Givertz MM. The association between high-dose diuretics and clinical stability in ambulatory chronic heart failure patients. J Card Fail. 2008 Jun;14(5):388-93. doi: 10.1016/j.cardfail.2008.01.015. Epub 2008 May 27.

    PubMed 18514930
  • Nohria A, Tsang SW, Fang JC, Lewis EF, Jarcho JA, Mudge GH, Stevenson LW. Clinical assessment identifies hemodynamic profiles that predict outcomes in patients admitted with heart failure. J Am Coll Cardiol. 2003 May 21;41(10):1797-804. doi: 10.1016/s0735-1097(03)00309-7.

    PubMed 12767667
  • Nagueh SF, Bhatt R, Vivo RP, Krim SR, Sarvari SI, Russell K, Edvardsen T, Smiseth OA, Estep JD. Echocardiographic evaluation of hemodynamics in patients with decompensated systolic heart failure. Circ Cardiovasc Imaging. 2011 May;4(3):220-7. doi: 10.1161/CIRCIMAGING.111.963496. Epub 2011 Mar 11.

    PubMed 21398512
  • Andersen OS, Smiseth OA, Dokainish H, Abudiab MM, Schutt RC, Kumar A, Sato K, Harb S, Gude E, Remme EW, Andreassen AK, Ha JW, Xu J, Klein AL, Nagueh SF. Estimating Left Ventricular Filling Pressure by Echocardiography. J Am Coll Cardiol. 2017 Apr 18;69(15):1937-1948. doi: 10.1016/j.jacc.2017.01.058.

    PubMed 28408024
  • Forrester JS, Diamond G, Chatterjee K, Swan HJ. Medical therapy of acute myocardial infarction by application of hemodynamic subsets (first of two parts). N Engl J Med. 1976 Dec 9;295(24):1356-62. doi: 10.1056/NEJM197612092952406. No abstract available.

    PubMed 790191
  • Stevenson LW, Perloff JK. The limited reliability of physical signs for estimating hemodynamics in chronic heart failure. JAMA. 1989 Feb 10;261(6):884-8.

    PubMed 2913385
  • Lechat P, Escolano S, Golmard JL, Lardoux H, Witchitz S, Henneman JA, Maisch B, Hetzel M, Jaillon P, Boissel JP, Mallet A. Prognostic value of bisoprolol-induced hemodynamic effects in heart failure during the Cardiac Insufficiency BIsoprolol Study (CIBIS). Circulation. 1997 Oct 7;96(7):2197-205. doi: 10.1161/01.cir.96.7.2197.

    PubMed 9337190
  • Hall SA, Cigarroa CG, Marcoux L, Risser RC, Grayburn PA, Eichhorn EJ. Time course of improvement in left ventricular function, mass and geometry in patients with congestive heart failure treated with beta-adrenergic blockade. J Am Coll Cardiol. 1995 Apr;25(5):1154-61. doi: 10.1016/0735-1097(94)00543-y.

    PubMed 7897129
  • Doughty RN, Whalley GA, Gamble G, MacMahon S, Sharpe N. Effects of carvedilol on left ventricular regional wall motion in patients with heart failure caused by ischemic heart disease. Australia-New Zealand Heart Failure Research Collaborative Group. J Card Fail. 2000 Mar;6(1):11-8. doi: 10.1016/s1071-9164(00)00007-5.

    PubMed 10746814
  • Konstam MA, Kronenberg MW, Rousseau MF, Udelson JE, Melin J, Stewart D, Dolan N, Edens TR, Ahn S, Kinan D, et al. Effects of the angiotensin converting enzyme inhibitor enalapril on the long-term progression of left ventricular dilatation in patients with asymptomatic systolic dysfunction. SOLVD (Studies of Left Ventricular Dysfunction) Investigators. Circulation. 1993 Nov;88(5 Pt 1):2277-83. doi: 10.1161/01.cir.88.5.2277.

    PubMed 8222122
  • Nicolosi GL, Latini R, Marino P, Maggioni AP, Barlera S, Franzosi MG, Geraci E, Santoro L, Tavazzi L, Tognoni G, Vecchio C, Volpi A. The prognostic value of predischarge quantitative two-dimensional echocardiographic measurements and the effects of early lisinopril treatment on left ventricular structure and function after acute myocardial infarction in the GISSI-3 Trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico. Eur Heart J. 1996 Nov;17(11):1646-56. doi: 10.1093/oxfordjournals.eurheartj.a014747.

    PubMed 8922912
  • Vardeny O, Claggett B, Kachadourian J, Desai AS, Packer M, Rouleau J, Zile MR, Swedberg K, Lefkowitz M, Shi V, McMurray JJV, Solomon SD. Reduced loop diuretic use in patients taking sacubitril/valsartan compared with enalapril: the PARADIGM-HF trial. Eur J Heart Fail. 2019 Mar;21(3):337-341. doi: 10.1002/ejhf.1402. Epub 2019 Feb 11.

    PubMed 30741494
  • Vardeny O, Claggett B, Kachadourian J, Pearson SM, Desai AS, Packer M, Rouleau J, Zile MR, Swedberg K, Lefkowitz M, Shi V, McMurray JJV, Solomon SD. Incidence, Predictors, and Outcomes Associated With Hypotensive Episodes Among Heart Failure Patients Receiving Sacubitril/Valsartan or Enalapril: The PARADIGM-HF Trial (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure). Circ Heart Fail. 2018 Apr;11(4):e004745. doi: 10.1161/CIRCHEARTFAILURE.117.004745.

    PubMed 29643067

Questions about this trial

What is this clinical trial studying?

An observational study of Heart Failure, Left Sided and Left Ventricular Dysfunction, run by Italian Society of Cardiology at 1 site in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 May 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change from baseline in Cardiac Output after 12 months of treatment (time frame: March, 16 th 2019 - March,16th 2020). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04397302, which also lists 22 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 May 2020.

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