Heart FailureOPTIMAVNCT06667128
Optimization of Heart Failure (HF) Medical Therapy After Transcatheter Valve Intervention (TVI) in Patients With Heart Failure With Reduced Ejection Fraction (HFrEF)
A study testing Rapid Uptitration of Guideline-Directed Medical Therapy, Elecsys® NT-proBNP - Roche Diagnostics and Rapid Up-Titration GDMT Group with Hospital Monitoring in people with Heart Failure and Valvulopathy, run by IRCCS Ospedale San Raffaele at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Heart Failure, Valvulopathy, Aortic Stenosis
- What is being tested?
- Rapid Uptitration of Guideline-Directed Medical Therapy, Elecsys® NT-proBNP - Roche Diagnostics and Rapid Up-Titration GDMT Group with Hospital Monitoring
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 160 participants
- Where
- 1 siteItaly
- Study dates
- 1 Feb 2025to 1 Feb 2026
- Phase
- Interventional
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 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 10Show fewer
- 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.
Who cannot join
- 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.
Show all 19Show fewer
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site
IRCCS Ospedale San Raffaele
Milan, 20132
Cosmo Godino, Co-PI, +39 3478497733, godino.cosmo@hsr.it
About this study
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.
Read the 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.
- Conditions
- Heart Failure, Valvulopathy, Aortic Stenosis, Aortic Regurgitation Disease, Mitral Regurgitation, Tricuspid Regurgitation
- Being tested
- Rapid Uptitration of Guideline-Directed Medical Therapy, Elecsys® NT-proBNP - Roche Diagnostics, Rapid Up-Titration GDMT Group with Hospital Monitoring
- Keywords
- Heart Failure, Aortic Stenosis, Aortic Regurgitation, Mitral Regurgitation, Tricuspid Regurgitation, Mitraclip, Triclip, TAVI
- Medical subject headings
- Heart Failure, Heart Valve Diseases, Aortic Valve Stenosis, Mitral Valve Insufficiency, Tricuspid Valve Insufficiency, Aortic Valve Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rapid Uptitration of Guideline-Directed Medical TherapyOther
Rapid up-titration of GDMT guided by protocol-specific guideline.
Elecsys® NT-proBNP - Roche DiagnosticsDiagnostic test
Also called Point-of-Care (PoC) Monitoring
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.
Rapid Up-Titration GDMT Group with Hospital MonitoringOther
Rapid Up-Titration GDMT Group guided by protocol-specific guideline and hospital monitoring.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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). Receives: Other: Rapid Up-Titration GDMT Group with Hospital Monitoring |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: From enrollment to the end of treatment (up to 6 months).
Secondary outcomes (6)
Incidence of cardiovascular death
The incidence of death attributable to cardiovascular causes, including sudden cardiac death, myocardial infarction, or worsening heart failure.
Measured: From enrollment to the end of treatment (up to 6 months).
Rate of Heart Failure Readmission
The rate of hospital readmission due to worsening heart failure symptoms, requiring inpatient care following discharge from the initial intervention.
Measured: From enrollment to the end of treatment (up to 6 months).
Composite endpoint of Heart Failure Readmission or All-Cause Death
A composite endpoint measuring the incidence of either heart failure-related hospital readmission or death from any cause.
Measured: 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
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).
Measured: From enrollment to the end of treatment (up to 6 months).
Change in Quality of Life according to the Kansas City Cardiomyopathy Questionnaire
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.
Measured: From enrollment to the end of treatment (up to 6 months).
Changes in NT-proBNP Levels
Evaluation of the reduction in NT-proBNP levels from baseline to study completion as a biomarker of heart failure status improvement.
Measured: From enrollment to the end of treatment (up to 6 months).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2024
- Study start1 Feb 2025 (estimated)
- Primary completion1 Feb 2026 (estimated)
- Study completion1 Feb 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- IRCCS Ospedale San Raffaele
- Sponsor type
- University, hospital or other
- Collaborators
- Hoffmann-La Roche
- Responsible party
- Principal investigator, Cosmo Godino, IRCCS Ospedale San Raffaele
- Investigators
- Francesco Maisano, Head of Cardiac Surgery, Principal investigator, IRCCS Ospedale San Raffaele
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06667128
- Sponsor's protocol ID
- 22071997
- Acronym
- OPTIMAV
- Status last verified
- Oct 2024
- First submitted
- 25 Oct 2024
- Last updated
- 4 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 34453165McDonagh 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.
PubMed 37622666Bettencourt 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.
PubMed 15451800Adamo 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.
PubMed 37217188Mebazaa 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.
PubMed 36356631Ben 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.
PubMed 35338542Holmes 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.
PubMed 25756438