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

October 31, 2024 updated by: Cosmo Godino, IRCCS Ospedale San Raffaele
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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

160

Phase

  • Not Applicable

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 Backup

Study Locations

  • Italy
      • Milan, Italy, 20132
        • IRCCS Ospedale San Raffaele
        • Contact:

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

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

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: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Standard Care Group
Participants receive standard follow-up care with Guideline-Directed Medical Therapy (GDMT) adjustments as per the physician's usual practice.
Experimental: Rapid Up-Titration GDMT Group with Point-of-Care (PoC) Monitoring
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
Rapid up-titration of GDMT guided by protocol-specific guideline.
Diagnostic test: Elecsys® NT-proBNP - Roche Diagnostics
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.
Other Names:
  • Point-of-Care (PoC) Monitoring
Experimental: Rapid Up-Titration GDMT Group with Hospital Monitoring
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
Rapid Up-Titration GDMT Group guided by protocol-specific guideline and hospital monitoring.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Composite Hierarchical Outcome for Mortality, Heart Failure Hospitalization, and NT-proBNP Response
Time Frame: From enrollment to the end of treatment (up to 6 months).
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Quality of Life according to the European Heart Failure Self-care Behaviour Scale
Time Frame: From enrollment to the end of treatment (up to 6 months).
Assessment of patient-reported quality of life changes using the European Heart Failure Self-care Behaviour Scale (EHFScBS), a 9-items scale where higher score means worse self care (possible range 9 - 45).
From enrollment to the end of treatment (up to 6 months).
Change in Quality of Life according to the Kansas City Cardiomyopathy Questionnaire
Time Frame: From enrollment to the end of treatment (up to 6 months).
Assessment of patient-reported quality of life changes using the Kansas City Cardiomyopathy Questionnaire (KCCQ), a validated health status measure for patients with heart failure. It contains four subdomains: Physical Limitation, Symptom Frequency, Quality of Life, and Social Limitations. Each subdomain provides an individual score from 0 to 100, with 0 denoting the worst and 100 the best possible health status.
From enrollment to the end of treatment (up to 6 months).
Changes in NT-proBNP Levels
Time Frame: From enrollment to the end of treatment (up to 6 months).
Evaluation of the reduction in NT-proBNP levels from baseline to study completion as a biomarker of heart failure status improvement.
From enrollment to the end of treatment (up to 6 months).
Incidence of cardiovascular death
Time Frame: From enrollment to the end of treatment (up to 6 months).
The incidence of death attributable to cardiovascular causes, including sudden cardiac death, myocardial infarction, or worsening heart failure.
From enrollment to the end of treatment (up to 6 months).
Rate of Heart Failure Readmission
Time Frame: From enrollment to the end of treatment (up to 6 months).
The rate of hospital readmission due to worsening heart failure symptoms, requiring inpatient care following discharge from the initial intervention.
From enrollment to the end of treatment (up to 6 months).
Composite endpoint of Heart Failure Readmission or All-Cause Death
Time Frame: From enrollment to the end of treatment (up to 6 months).
A composite endpoint measuring the incidence of either heart failure-related hospital readmission or death from any cause.
From enrollment to the end of treatment (up to 6 months).

Collaborators and Investigators

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

Sponsor

IRCCS Ospedale San Raffaele

Collaborators

Hoffmann-La Roche

Investigators

  • Principal Investigator: Francesco Maisano, Head of Cardiac Surgery, IRCCS Ospedale San Raffaele

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 (Estimated)

February 1, 2025

Primary Completion (Estimated)

February 1, 2026

Study Completion (Estimated)

February 1, 2026

Study Registration Dates

First Submitted

October 25, 2024

First Submitted That Met QC Criteria

October 29, 2024

First Posted (Actual)

October 31, 2024

Study Record Updates

Last Update Posted (Estimated)

November 4, 2024

Last Update Submitted That Met QC Criteria

October 31, 2024

Last Verified

October 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 22071997

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

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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