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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if biomarker levels, such as NTproBNP (a protein related to heart stress), can improve hospital discharge planning for individuals with acute decompensated heart failure. Participants will be divided into two groups: one will follow a biomarker-guided discharge plan, while the other will receive usual care. The goal is to assess whether the biomarker-based approach enables patients to leave the hospital safely and maintain their health longer. Individuals hospitalized due to sudden worsening of heart failure might be suitable candidates for this study. As an unphased trial, this study provides a unique opportunity to contribute to innovative research that could enhance future heart failure care.

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 prior data suggests that this biomarker guided discharge algorithm is safe for heart failure patients?

Research has shown that using biomarkers like NTproBNP to guide treatment in heart failure patients is generally well-tolerated and safe. NTproBNP, a protein, helps doctors assess heart failure severity. Past studies have not reported major safety issues with this approach.

For example, patients in similar studies did not experience more side effects than those receiving standard care, suggesting that the biomarker-guided method is as safe as usual treatments. While some studies found that targeting specific NTproBNP levels didn't significantly change outcomes, they did not report increased risks or safety problems.

Overall, the biomarker-guided approach appears safe based on available research. Participants in these studies have not shown significant adverse effects compared to those receiving regular care. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the biomarker-guided discharge algorithm for heart failure because it customizes the timing of patient discharge based on specific blood markers, namely NTproBNP levels. Unlike the usual care, where discharge decisions are largely based on clinical judgment without biomarker input, this method aims to optimize and potentially shorten hospital stays by providing a more tailored approach to each patient's condition. This personalized strategy could lead to better resource utilization and improved patient outcomes, making it a promising advancement in heart failure management.

What evidence suggests that the biomarker guided discharge algorithm is effective for heart failure?

Research has shown that using indicators like NTproBNP to guide heart failure treatment can be very effective. In this trial, participants in the biomarker-guided discharge pathway will have their NTproBNP levels monitored to optimize discharge timing. Studies have found that this method might reduce hospital visits and lower death rates in heart failure patients. NTproBNP, a substance produced by the heart under stress, helps doctors make better treatment decisions when its levels are checked. This approach is also more cost-effective than standard care. Overall, this method shows promise for improving outcomes in heart failure patients. ^{1 2 5 6 7}

Who Is on the Research Team?

Peter Liu, MD

Principal Investigator

Ottawa Heart Institute Research Corporation

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5490943/

Biomarker Guided Therapy in Chronic Heart Failure - PMC This review article addresses the question of whether biomarker-guided therapy is ready for clinical implementation in chronic heart failure.

2. withpower.com withpower.com/trial/phase-heart-failure-7-2017-70793

Biomarker-Guided Discharge for Heart Failure (RADAR Trial) Using biomarkers like BNP and NT pro-BNP to guide treatment in chronic heart failure patients may reduce hospital readmissions and lower mortality rates, ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT00351390

Use of NT-proBNP Testing to Guide Heart Failure Therapy ... The goal of the PROTECT study is to evaluate whether treatment of patients with advanced and recently destabilized HF would benefit from NT-proBNP guided HF ...

4. academic.oup.com academic.oup.com/eurheartj/article/35/1/16/441442

Natriuretic peptide-guided heart failure management Biomarker guided care was more likely to be cost effective than standard management ... Heart failure outcomes and benefits of NT-proBNP-guided management in the ...

5. jacc.org jacc.org/doi/10.1016/j.jchf.2014.05.007

Guiding Evidence Based Therapy Using Biomarker ... The GUIDE-IT (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure) study is designed to determine the ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6911833/

Targeting Natriuretic Peptide Levels in Heart Failure with ... Abstract. Purpose of review: Explore controversial biomarker-guided management of patients with heart failure (HF) with reduced ejection fraction.

7. ahajournals.org ahajournals.org/doi/10.1161/circulationaha.117.029882

NT-proBNP (N-Terminal pro-B-Type Natriuretic Peptide) We demonstrate that NT-proBNP-guided therapy targeting an NT-proBNP reduction of >30% did not improve clinical outcomes.