Biomarker-Guided Discharge for Heart Failure

(RADAR Trial)

Overseen By Ermina Moga, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Peter Liu

Disqualifiers: End stage organ failure, Transplant, Cardiogenic shock, Life expectancy <6 months, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

Duration: 1-2 weeks

750 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a multi-centre, single blind, randomized study. Patients admitted to hospital with acute decompensated heart failure will be randomized to biomarker guided discharge algorithm vs usual care in a 2:1 ratio. NTproBNP and other biomarkers will be measured within 24 hours of admission. The NTproBNP results will be used to further stratify participants randomized to the biomarker guided group into lower and medium to higher risk pathways. Biomarkers will be repeated after 2-3 days and again prior to discharge. Specific care pathways will be followed for each of the lower risk and medium-higher risk groups. Biomarkers will be repeated 30 days post discharge. Participants will be followed with a phone call at 3 months and return for a follow up visit at 6 months post discharge for outcome evaluation.

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What data supports the effectiveness of the treatment Biomarker guided discharge algorithm, NT-proBNP guided discharge, Biomarker guided heart failure management?

Research shows that using biomarkers like NT-proBNP to guide heart failure treatment can lead to fewer hospital readmissions and lower death rates from heart failure. This approach helps doctors adjust medications more effectively, improving patient outcomes and quality of life. ^{1 2 3 4 5}

Is biomarker-guided discharge for heart failure safe for humans?

Studies on biomarker-guided care for heart failure, using markers like NT-proBNP, show that it is generally well tolerated and does not lead to more adverse outcomes compared to standard care. Patients receiving this type of care often experience improved quality of life and better heart function without additional safety concerns. ^{2 5 6 7 8}

How is the biomarker-guided discharge treatment for heart failure different from other treatments?

This treatment uses levels of a specific biomarker, NT-proBNP, to guide decisions about when to discharge heart failure patients, aiming to improve outcomes by ensuring patients are stable before leaving the hospital. Unlike standard treatments that rely on clinical judgment alone, this approach provides an objective measure to tailor and intensify care, potentially leading to better quality of life and fewer complications. ^{2 3 5 8 9}

Research Team

Peter Liu, MD

Principal Investigator

Ottawa Heart Institute Research Corporation

Eligibility Criteria

This trial is for hospital-admitted patients with acute decompensated heart failure who meet the modified Framingham criteria. Excluded are those unable to give blood samples, follow-up, or with end-stage organ failure, listed for a heart transplant, conditions complicating discharge, in another recent trial, severe lung issues requiring intubation, extremely high NTproBNP levels, in cardiogenic shock or with less than 6 months to live.

Inclusion Criteria

I was hospitalized for worsening heart failure.

Exclusion Criteria

I need a tube to help me breathe.

My organs are failing and cannot be recovered.

I am on the heart transplant list or being evaluated for it.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Participants receive treatment based on NTproBNP levels, with repeated biomarker measurements and discharge planning

1-2 weeks

Daily monitoring (in-person)

Follow-up

Participants are monitored for safety and effectiveness after discharge, with biomarker measurements and quality of life assessments

6 months

1 phone call, 1 visit (in-person)

Long-term follow-up

Participants are monitored for long-term outcomes and cost savings

2 years

Treatment Details

Interventions

• Biomarker guided discharge algorithm

Trial Overview The study tests a biomarker guided discharge algorithm against usual care for heart failure patients. It's single-blind and randomizes participants in a 2:1 ratio. Biomarkers like NTproBNP are measured at admission and guide treatment pathways; they're checked again during hospital stay and after one month post-discharge.

Participant Groups

Group I: Biomarker guided discharge pathway Experimental Treatment 1 Intervention

Admission NTproBNP levels will be used to stratify participants into lower and medium-higher risk care pathways. NTproBNP levels will be repeated on Day 2-3 and again prior to discharge. Each care pathway is designed to optimize discharge time according to NTproBNP levels. All NTproBNP results will be displayed on the front of the participant's chart along with the care pathway that the participant has been randomized to. The care providers will be reminded daily by the study team that the participant is in the biomarker guided discharge pathway arm of the study and that the designated care pathway should be followed as closely as possible.

Group II: Usual care Active Control 1 Intervention

Participants will be treated as is usual at each institution. Biomarkers will be measured on Day 2-3 and again prior to discharge from hospital. NTproBNP levels will not be revealed to care providers.

Who Is Running the Clinical Trial?

Peter Liu

Lead Sponsor

Trials

1

Recruited

750+

Roche Diagnostics GmbH

Industry Sponsor

Trials

68

Recruited

668,000+

Dr. Thomas Schinecker

Roche Diagnostics GmbH

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Dr. Levi Garraway

Roche Diagnostics GmbH

Chief Medical Officer since 2019

MD from Harvard Medical School

Genome Canada

Collaborator

Trials

17

Recruited

34,400+

Roche Diagnostics

Industry Sponsor

Trials

55

Recruited

652,000+

Ottawa Heart Institute Research Corporation

Collaborator

Trials

200

Recruited

95,800+

Findings from Research

Using biomarkers like BNP and NT pro-BNP to guide treatment in chronic heart failure patients may reduce hospital readmissions and lower mortality rates, although this benefit does not extend to patients over 75 years old.

The effectiveness of biomarker-guided treatment appears to stem from improved adherence to recommended medication dosages and treatment guidelines, suggesting that enhancing physician compliance with these guidelines could be more beneficial than solely focusing on biomarker levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[BNP-guided therapy of chronic heart failure: what is the evidence?]. Copt, C., Nendaz, M.[2009]

Biomarker-guided care using natriuretic peptides like BNP and NT-proBNP leads to more aggressive and effective treatment for heart failure, achieving lower target concentrations without increasing adverse outcomes.

Patients receiving biomarker-guided therapy not only experienced better management of their heart failure but also showed improved quality of life and better heart function on echocardiograms compared to those receiving standard care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of natriuretic peptide testing in guiding chronic heart failure management: review of available data and recommendations for use. Januzzi, JL.[2015]

Natriuretic peptides, specifically BNP and NT-proBNP, are valuable biomarkers for diagnosing and monitoring heart failure (HF) treatment, showing changes that reflect the effectiveness of therapies applied.

Guideline-directed medical therapy that aims to suppress BNP and NT-proBNP levels below certain thresholds has been associated with better patient outcomes and is recommended in US HF guidelines, indicating a promising approach for optimizing heart failure care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Natriuretic peptide-guided heart failure management. Troughton, R., Michael Felker, G., Januzzi, JL.[2022]

In a study of 166 ambulatory heart failure patients, both the NT-proBNP level measured three months after discharge and the percent change from discharge were found to be significant predictors of death or rehospitalization, with 38% of patients reaching this endpoint during a mean follow-up of 14 months.

The prognostic value of NT-proBNP measurements varies: in patients with high NT-proBNP levels, the recent percent change is a strong predictor of outcomes, while in those with low levels, the current NT-proBNP value is the only significant predictor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic value of sequential measurements of amino-terminal prohormone of B-type natriuretic peptide in ambulatory heart failure patients. Moertl, D., Hammer, A., Huelsmann, M., et al.[2022]

In a study of 271 patients with acute heart failure, NT-proBNP-guided therapy, which involved intensifying treatment based on NT-proBNP levels, did not significantly improve outcomes compared to standard care.

However, a decrease in NT-proBNP levels from predischarge to discharge was found to be an independent predictor of better outcomes, indicating that monitoring NT-proBNP could still be valuable in assessing patient prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

N-terminal pro-B-type natriuretic peptide-guided therapy in patients hospitalized for acute heart failure. Carubelli, V., Lombardi, C., Lazzarini, V., et al.[2017]

In a study of 108,330 heart failure patients, NT-proBNP levels were found to reliably predict clinical outcomes, supporting its use as a surrogate marker in heart failure trials.

The analysis showed that early NT-proBNP measurements can effectively forecast hazard ratios for clinical events, allowing for shorter and smaller heart failure trials without compromising reliability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NT-proBNP Qualifies as a Surrogate for Clinical End Points in Heart Failure. Schmitt, W., Rühs, H., Burghaus, R., et al.[2021]

Natriuretic peptides like BNP and NT-proBNP are valuable for diagnosing and predicting outcomes in chronic heart failure, leading to the hypothesis that therapy guided by these biomarkers could improve clinical results compared to traditional symptom-based approaches.

In a study of 52 patients with chronic heart failure, those treated based on BNP levels experienced fewer cardiovascular events than those treated based on clinical symptoms, although this difference was not statistically significant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Will the therapy of chronic heart failure be guided by plasma levels of natriuretic peptides?]. Hradec, J., Krupicka, J., Janota, T.[2015]

Chronic heart failure (HF) treatment currently relies heavily on clinical judgment, leading to significant treatment gaps and high risks of morbidity and mortality, indicating a need for improved management strategies.

Natriuretic peptides serve as important biomarkers for HF, and their use in 'biomarker-guided' care could help identify patients needing intensified therapy and provide objective monitoring of disease status, potentially improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of natriuretic peptides as biomarkers for guiding the management of chronic heart failure. Motiwala, SR., Januzzi, JL.[2022]

The GUIDE-IT trial, involving 894 patients with heart failure and reduced ejection fraction, found that an NT-proBNP-guided treatment strategy did not significantly improve quality of life compared to usual care over 24 months.

The NT-proBNP-guided strategy resulted in higher total costs, averaging $5,919 more than usual care, without demonstrating additional benefits in patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Economic and Quality-of-Life Outcomes of Natriuretic Peptide-Guided Therapy for Heart Failure. Mark, DB., Cowper, PA., Anstrom, KJ., et al.[2021]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

[BNP-guided therapy of chronic heart failure: what is the evidence?]. [2009]

2. Netherlands pubmed.ncbi.nlm.nih.gov

The role of natriuretic peptide testing in guiding chronic heart failure management: review of available data and recommendations for use. [2015]

3. England pubmed.ncbi.nlm.nih.gov

Natriuretic peptide-guided heart failure management. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Prognostic value of sequential measurements of amino-terminal prohormone of B-type natriuretic peptide in ambulatory heart failure patients. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

N-terminal pro-B-type natriuretic peptide-guided therapy in patients hospitalized for acute heart failure. [2017]

6. United States pubmed.ncbi.nlm.nih.gov

NT-proBNP Qualifies as a Surrogate for Clinical End Points in Heart Failure. [2021]

7. Czech Republic pubmed.ncbi.nlm.nih.gov

[Will the therapy of chronic heart failure be guided by plasma levels of natriuretic peptides?]. [2015]

8. United States pubmed.ncbi.nlm.nih.gov

The role of natriuretic peptides as biomarkers for guiding the management of chronic heart failure. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Economic and Quality-of-Life Outcomes of Natriuretic Peptide-Guided Therapy for Heart Failure. [2021]