Clinical trial NCT06667128: Optimization of Heart Failure (HF) Medical Therapy After Transcatheter Valve Intervention (TVI) in Patients With Heart Failure With Reduced Ejection Fraction (HFrEF)
Official title: Optimization of Heart Failure (HF) Medical Therapy After Transcatheter Valve Intervention (TVI) in Patients With Heart Failure With Reduced Ejection Fraction (HFrEF)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
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
Lead sponsor: IRCCS Ospedale San Raffaele
Sponsor class: OTHER
Collaborators: name: Hoffmann-La Roche
First posted: 2024-10-31
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: Heart valve disease, with a current prevalence of 2.5% that rises with age, has been described as "the next cardiac epidemic", and is projected to double by 2040 and triple by 2060, paralleling population aging.

The period during and immediately after hospitalization for transcatheter valve intervention (TVI) in HFrEF patients (LVEF ≤ 40%) represents a "vulnerable phase" characterized by a high risk of death and re-hospitalization for acute HF. A study from the TVI registry demonstrated that, among 12.182 patients treated with TAVR in the United States, the rate of HF readmission at 1 year was 14.3% and the 1-year overall mortality was 23.7%.

Moreover, the CHOICE-MI registry demonstrated that the primary combined endpoint of all-cause mortality or HF hospitalization at 1 year occurred in 39.2% of the Transcatheter mitral valve implantation (TMVI) patients, and in 28% in those TMVI-ineligible who undergoing bailout-TEER.

Recently, the STRONG-HF trial demonstrated that rapid, intensive up-titration of guideline-directed therapy, coupled with close post-discharge follow-up, significantly enhances life quality and reduces 180-day mortality and heart failure readmission rates versus usual care.

Previous studies have additionally shown that a decrease in NT-proBNP levels during hospitalization for acute HF is associated with improved survival and reduced readmission rates. Patients whose NT-proBNP levels decrease by at least 30% tend to have a better prognosis compared to those with no significant change or an increase in levels. This suggests that a meaningful decrease in NT-proBNP levels can indicate successful response to HF treatment.

Consequently, guiding HF therapy based on NT-proBNP levels can potentially improve clinical outcomes. For instance, adjusting medications to achieve a target NT-proBNP level may result in better control of HF symptoms and a lower risk of hospital readmission and mortality. This approach emphasizes the role of NT-proBNP as not just a diagnostic and prognostic tool but also as a therapeutic target in HF management. Overall, the use of NT-proBNP monitoring to guide medical therapy in HF patients supports a more personalized treatment strategy, potentially leading to rapid and effective decongestion, optimized therapy, and improved patient outcomes.

Hence, the primary objective of this study is to assess the impact of rapid up-titration of Guideline-Directed Medical Therapy (GDMT) in patients with HFrEF undergoing transcatheter valvular intervention, supplemented by close follow-up visits and NT-proBNP measurements, using a hierarchical composite endpoint, which prioritize (1) all-cause mortality, (2) number of hospitalizations for heart failure, and (3) improvement in NT-proBNP, defined as a decrease of at least 30% from the baseline value.

Eligibility criteria: Inclusion Criteria:

* 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):

  1. NT-proBNP \> 900 pg/mL.
  2. Systolic blood pressure ≥ 100 mmHg.
  3. Heart rate ≥ 60 bpm.
  4. 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.

Exclusion Criteria:

* 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.
* Prior (defined as less than 30 days from screening) or current enrollment in a CHF trial or participation in an investigational drug or device study within the 30 days prior to screening.
* Discharge to a rehabilitation of long-term care facility.
* Inability to comply with all study requirements, due to major co-morbidities, social or financial issues, or a history of noncompliance with medical regimens, that might compromise the patient's ability to understand and/or comply with the protocol instructions or follow-up procedures
* Pregnant or nursing (lactating) women.

Primary outcomes:
measure: Composite Hierarchical Outcome for Mortality, Heart Failure Hospitalization, and NT-proBNP Response
timeFrame: From enrollment to the end of treatment (up to 6 months).
Secondary outcomes:
measure: Incidence of cardiovascular death
timeFrame: From enrollment to the end of treatment (up to 6 months).
measure: Rate of Heart Failure Readmission
timeFrame: From enrollment to the end of treatment (up to 6 months).
measure: Composite endpoint of Heart Failure Readmission or All-Cause Death
timeFrame: From enrollment to the end of treatment (up to 6 months).
measure: Change in Quality of Life according to the European Heart Failure Self-care Behaviour Scale
timeFrame: From enrollment to the end of treatment (up to 6 months).
measure: Change in Quality of Life according to the Kansas City Cardiomyopathy Questionnaire
timeFrame: From enrollment to the end of treatment (up to 6 months).
measure: Changes in NT-proBNP Levels
timeFrame: From enrollment to the end of treatment (up to 6 months).
Other outcomes:
Locations:
city: Milan
country: Italy
facility: IRCCS Ospedale San Raffaele
Study officials:
affiliation: IRCCS Ospedale San Raffaele
name: Francesco Maisano, Head of Cardiac Surgery
role: PRINCIPAL_INVESTIGATOR
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