Optimization of Heart Failure (HF) Medical Therapy After Transcatheter Valve Intervention (TVI) in Patients With Heart Failure With Reduced Ejection Fraction (HFrEF)

NCT06667128 | Not Yet Recruiting DMC

• 1 other identifier: 22071997
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

This trial is a single-center, open-label, randomized study designed to assess the impact of a rapid up-titration of Guideline-Directed Medical Therapy (GDMT) on heart failure with reduced ejection fraction (HFrEF) patients following transcatheter valve interventions. The study focuses on the efficacy of intensive treatment in decreasing NT-proBNP levels and improving patient outcomes, including survival rates and quality of life over a six-month period. Patients are closely monitored using both Point-of-Care technology and hospital-based assessments, with the goal of enhancing GDMT adjustments. This approach is compared to standard care to determine its potential benefits in the management of HFrEF post-valve intervention.

Conditions

Heart Failure; Valvulopathy; Aortic Stenosis; Aortic Regurgitation Disease; Mitral Regurgitation; Tricuspid Regurgitation; Brain Natriuretic Peptide; Mitraclip; TAVI(Transcatheter Aortic Valve Implantation)

Keywords

Heart Failure; Aortic Stenosis; Aortic Regurgitation; Mitral Regurgitation; Tricuspid Regurgitation; Mitraclip; Triclip; TAVI

Outcome Measures

Primary Outcomes (1)

• Composite Hierarchical Outcome for Mortality, Heart Failure Hospitalization, and NT-proBNP Response

  Hierarchical composite endpoint composed of (1) all-cause death, (2) number of HF hospitalization, (3) improvement of NT-proBNP (with an improvement defined as a decrease of at least 30% from baseline).

  From enrollment to the end of treatment (up to 6 months).

Secondary Outcomes (6)

• Incidence of cardiovascular death

  From enrollment to the end of treatment (up to 6 months).

• Rate of Heart Failure Readmission

  From enrollment to the end of treatment (up to 6 months).

• Composite endpoint of Heart Failure Readmission or All-Cause Death

  From enrollment to the end of treatment (up to 6 months).

• Change in Quality of Life according to the European Heart Failure Self-care Behaviour Scale

  From enrollment to the end of treatment (up to 6 months).

• Change in Quality of Life according to the Kansas City Cardiomyopathy Questionnaire

  From enrollment to the end of treatment (up to 6 months).

Study Arms (3)

Standard Care Group

NO INTERVENTION

Participants receive standard follow-up care with Guideline-Directed Medical Therapy (GDMT) adjustments as per the physician's usual practice.

Rapid Up-Titration GDMT Group with Point-of-Care (PoC) Monitoring

EXPERIMENTAL

Patients will undergo rapid up-titration of GDMT. Their progress will be closely monitored using Point-of-Care (PoC) technology from Roche Diagnostics for NT-proBNP measurements.

Other: Rapid Uptitration of Guideline-Directed Medical Therapy; Diagnostic Test: Elecsys® NT-proBNP - Roche Diagnostics

Rapid Up-Titration GDMT Group with Hospital Monitoring

EXPERIMENTAL

Patients will undergo rapid up-titration of GDMT. Their progress will be closely monitored using hospital-based blood tests (Roche Elecsys central laboratory platform).

Other: Rapid Up-Titration GDMT Group with Hospital Monitoring

Interventions

Rapid Uptitration of Guideline-Directed Medical Therapy OTHER

Rapid up-titration of GDMT guided by protocol-specific guideline.

Rapid Up-Titration GDMT Group with Point-of-Care (PoC) Monitoring

Elecsys® NT-proBNP - Roche Diagnostics DIAGNOSTIC_TEST

An assay provided by Roche (Elecsys® NT-proBNP - Roche Diagnostics) will be used to assess NT-proBNP levels in the Rapid Up-Titration GDMT Group with Point-of-Care (PoC) Monitoring, with the purpose of evaluating any differences in marker dosage between the indicated method and the monitoring by the hospital laboratory analysis.

Also known as: Point-of-Care (PoC) Monitoring

Rapid Up-Titration GDMT Group with Point-of-Care (PoC) Monitoring

Rapid Up-Titration GDMT Group with Hospital Monitoring OTHER

Rapid Up-Titration GDMT Group guided by protocol-specific guideline and hospital monitoring.

Rapid Up-Titration GDMT Group with Hospital Monitoring

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Hospital admission for severe symptomatic valve disease (aortic stenosis, mitral regurgitation, or tricuspid regurgitation) effectively treated with transcatheter valve intervention (TVI) during hospitalization.
• Chronic heart failure with reduced ejection fraction (HFrEF)
• At the time of randomization (1-2 days prior to discharge):
• NT-proBNP \> 900 pg/mL.
• Systolic blood pressure ≥ 100 mmHg.
• Heart rate ≥ 60 bpm.
• Serum potassium ≤ 5.0 mEq/L (mmol/L).
• At the time of hospital admission treated with ≤ ½ of the of optimal dose of ACEi/ARB/ARNi, ≤ ½ of the of optimal dose of beta-blocker, and ≤ ½ of the of optimal dose of MRA, either with or without SGLT2ic.
• Residency in the Lombardy region.
• Written informed consent to participate in the study.

You may not qualify if:

• Age \< 18 or \> 85 years.
• Clearly documented intolerance to ACEi/ARB/ARNI, or beta-blockers, or MRA, or SGLT2i.
• Residual severe valve disease of the valve treated with TVI (i.e. severe aortic stenosis or severe paravalvular leak after TAVR, severe mitral stenosis or severe residual mitral regurgitation after mitral valve intervention, or severe tricuspid stenosis or severe residual tricuspid regurgitation after tricuspid valve intervention).
• Presence at the time of randomization (1-2 days prior to discharge) of any severe valve disease.
• Hemodynamically significant obstructive lesion of the left ventricular outflow tract.
• Significant pulmonary disease contributing substantially to the patients' dyspnea such as FEV1\< 1 liter or need for chronic systemic or non-systemic steroid therapy, or any kind of primary right HF such as primary pulmonary hypertension or recurrent pulmonary embolism.
• Myocardial infarction, unstable angina or cardiac surgery within 3 months, or cardiac resynchronization therapy device implantation within 3 months, or percutaneous transluminal coronary intervention, within 1 month prior to screening.
• Uncorrected thyroid disease, active myocarditis, or known amyloid or hypertrophic obstructive cardiomyopathy.
• History of heart transplant or on a transplant list or using or planned to be implanted with a ventricular assist device.
• Sustained ventricular arrhythmia with syncopal episodes within the 3 months prior to screening that is untreated.
• Active infection at any time during hospitalization requiring intravenous antibiotics.
• Stroke or TIA within 3 months prior to screening.
• Primary liver disease considered to be life threatening.
• Renal disease or eGFR \< 30 mL/min/1.73m2 (as estimated by the simplified MDRD formula) at screening or history of dialysis.
• Psychiatric or neurological disorder, cirrhosis, or active malignancy leading to a life expectancy \<12 months.

Sponsors & Collaborators

• IRCCS Ospedale San Raffaele: lead
• Hoffmann-La Roche: collaborator

Study Sites (1)

IRCCS Ospedale San Raffaele

Milan, 20132, Italy

Location

Related Publications (7)

• Vahanian A, Beyersdorf F, Praz F, Milojevic M, Baldus S, Bauersachs J, Capodanno D, Conradi L, De Bonis M, De Paulis R, Delgado V, Freemantle N, Gilard M, Haugaa KH, Jeppsson A, Juni P, Pierard L, Prendergast BD, Sadaba JR, Tribouilloy C, Wojakowski W; ESC/EACTS Scientific Document Group. 2021 ESC/EACTS Guidelines for the management of valvular heart disease. Eur Heart J. 2022 Feb 12;43(7):561-632. doi: 10.1093/eurheartj/ehab395. No abstract available.

  PMID: 34453165 BACKGROUND

• McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Bohm M, Burri H, Butler J, Celutkiene J, Chioncel O, Cleland JGF, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Skibelund AK; ESC Scientific Document Group. 2023 Focused Update of the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2023 Oct 1;44(37):3627-3639. doi: 10.1093/eurheartj/ehad195. No abstract available.

  PMID: 37622666 BACKGROUND

• Bettencourt P, Azevedo A, Pimenta J, Frioes F, Ferreira S, Ferreira A. N-terminal-pro-brain natriuretic peptide predicts outcome after hospital discharge in heart failure patients. Circulation. 2004 Oct 12;110(15):2168-74. doi: 10.1161/01.CIR.0000144310.04433.BE. Epub 2004 Sep 27.

  PMID: 15451800 BACKGROUND

• Adamo M, Pagnesi M, Mebazaa A, Davison B, Edwards C, Tomasoni D, Arrigo M, Barros M, Biegus J, Celutkiene J, Cerlinskaite-Bajore K, Chioncel O, Cohen-Solal A, Damasceno A, Diaz R, Filippatos G, Gayat E, Kimmoun A, Lam CSP, Novosadova M, Pang PS, Ponikowski P, Saidu H, Sliwa K, Takagi K, Ter Maaten JM, Voors A, Cotter G, Metra M. NT-proBNP and high intensity care for acute heart failure: the STRONG-HF trial. Eur Heart J. 2023 Aug 14;44(31):2947-2962. doi: 10.1093/eurheartj/ehad335.

  PMID: 37217188 BACKGROUND

• Mebazaa A, Davison B, Chioncel O, Cohen-Solal A, Diaz R, Filippatos G, Metra M, Ponikowski P, Sliwa K, Voors AA, Edwards C, Novosadova M, Takagi K, Damasceno A, Saidu H, Gayat E, Pang PS, Celutkiene J, Cotter G. Safety, tolerability and efficacy of up-titration of guideline-directed medical therapies for acute heart failure (STRONG-HF): a multinational, open-label, randomised, trial. Lancet. 2022 Dec 3;400(10367):1938-1952. doi: 10.1016/S0140-6736(22)02076-1. Epub 2022 Nov 7.

  PMID: 36356631 BACKGROUND

• Ben Ali W, Ludwig S, Duncan A, Weimann J, Nickenig G, Tanaka T, Coisne A, Vincentelli A, Makkar R, Webb JG, Akodad M, Muller DWM, Praz F, Wild MG, Hausleiter J, Goel SS, von Ballmoos MW, Denti P, Chehab O, Redwood S, Dahle G, Baldus S, Adam M, Ruge H, Lange R, Kaneko T, Leroux L, Dumonteil N, Tchetche D, Treede H, Flagiello M, Obadia JF, Walther T, Taramasso M, Sondergaard L, Bleiziffer S, Rudolph TK, Fam N, Kempfert J, Granada JF, Tang GHL, von Bardeleben RS, Conradi L, Modine T; CHOICE-MI Investigators. Characteristics and outcomes of patients screened for transcatheter mitral valve implantation: 1-year results from the CHOICE-MI registry. Eur J Heart Fail. 2022 May;24(5):887-898. doi: 10.1002/ejhf.2492. Epub 2022 Apr 17.

  PMID: 35338542 BACKGROUND

• Holmes DR Jr, Brennan JM, Rumsfeld JS, Dai D, O'Brien SM, Vemulapalli S, Edwards FH, Carroll J, Shahian D, Grover F, Tuzcu EM, Peterson ED, Brindis RG, Mack MJ; STS/ACC TVT Registry. Clinical outcomes at 1 year following transcatheter aortic valve replacement. JAMA. 2015 Mar 10;313(10):1019-28. doi: 10.1001/jama.2015.1474.

  PMID: 25756438 BACKGROUND

MeSH Terms

Conditions

Heart Failure; Heart Valve Diseases; Aortic Valve Stenosis; Mitral Valve Insufficiency; Tricuspid Valve Insufficiency; Aortic Valve Insufficiency

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Aortic Valve Disease; Ventricular Outflow Obstruction

Study Officials

• Francesco Maisano, Head of Cardiac Surgery

  IRCCS Ospedale San Raffaele

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Francesco Maisano, PI

CONTACT

+39 3478497733; maisano.francesco@hsr.it

Cosmo Godino, Co-PI

CONTACT

+39 3478497733; godino.cosmo@hsr.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Doctor (Co-PI)

Study Record Dates

• First Submitted: October 25, 2024
• First Posted: October 31, 2024
• Study Start: February 1, 2025
• Primary Completion: February 1, 2026
• Study Completion: February 1, 2026
• Last Updated: November 4, 2024

Record last verified: 2024-10

Locations

IT (1)