Improving Diagnostic Accuracy for Acute Heart Failure (INDICATE-HF)

July 1, 2026 updated by: Deepak Gupta, Vanderbilt University Medical Center
Acute heart failure is a common reason for emergency department visits and hospitalization, but the diagnosis can be challenging because of non-specific symptoms and signs. The current diagnostic approach to acute heart failure has modest accuracy, leading to delayed diagnosis and treatment, which associate with worse prognosis. Prior work suggests diagnostic accuracy can be improved with the addition of multiple circulating biomarkers discovered through proteomics, and this study will derive and validate a multi-marker model to improve diagnostic accuracy for acute heart failure in the emergency department.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Detailed Description

Acute heart failure (HF) is highly morbid, lethal, and costly. It is a difficult diagnosis to make given its symptoms and signs overlap with other cardiac and non-cardiac conditions. In the emergency department (ED), misdiagnosis of acute HF is common and associated with adverse outcomes. Biomarker testing can facilitate accurate diagnosis; however, natriuretic peptides (NP) are the only guideline recommend biomarker of HF for diagnostic testing, and are better for ruling-out, rather than ruling-in, acute HF. Even with NP testing, in contemporary clinical practice misdiagnosis of acute HF still occurs in 10 to 45% of patients presenting to the ED with dyspnea. Clinical prediction models including multiple biomarkers hold promise for improving diagnostic accuracy. The few prior studies investigating a multiple biomarker approach for diagnosing acute HF were limited by constraint to highly correlated markers from known biologic pathways, relatively small sample sizes, lack of inclusion of all a priori selected biomarkers into a single model, and absence of validation cohorts. The current study is designed to address these limitations. Recent advances in "omics" enable novel biomarker discovery on a larger scale and investigations less "biased" by existing knowledge. The overarching hypothesis of this study is that a multi-marker model incorporating novel proteins discovered with plasma proteomics improves diagnostic accuracy for acute HF. In a preliminary proof of concept study plasma proteomics was utilized to discover a multi-marker panel of 21 biomarkers which improved diagnostic accuracy for acute HF beyond current clinical practice using clinical data and NP levels. These promising preliminary data motivate broader discovery in a larger sample size with subsequent derivation and validation of a multi-marker model for diagnosing acute HF in independent samples of adequate size. The specific aims of this study are to: 1) discover a multi-marker panel of 21 biomarkers to improve diagnostic accuracy for acute HF, 2) derive a model for diagnosing acute HF incorporating the 21-biomarker panel, and 3) test performance of the multi-marker model in a prospective validation cohort. In aim 1, existing plasma samples from ~900 patients will be used to assay 925 proteins to discover a smaller set of novel biomarkers most strongly associated with an adjudicated acute HF diagnosis. In aim 2, an existing prospective observational cohort, EMROC-AHF, will be utilized to derive the multi-marker model in ~900 patients who presented to the ED with acute dyspnea. In aim 3, from four EDs in Detroit, MI and Nashville, TN a new sample will prospectively recruit ~1,000 patients presenting with acute dyspnea and adjudicate the presence of acute HF by cardiologist panel review. Given the burden of HF, the frequency of inaccurate diagnosis and its adverse consequences, this study will address a significant unmet need by improving diagnostic accuracy for acute HF.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
2469

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

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Deepak K Gupta, MD, MSCI
  • Phone Number: 6159362530 6159362530
  • Email: d.gupta@vumc.org

Study Contact Backup

Study Locations

  • United States
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University Medical Center

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Adults (18 years or older) presenting with the chief complaint of dyspnea and in whom the ED physician is considering the diagnosis of acute HF, based on an order for measurement of NP levels (either BNP or NT-proBNP) or a chest x-ray will be included. Patients whose dyspnea is due to trauma, those who are on chronic hemodialysis, and patients whose primary presentation is consistent with acute coronary syndrome will be excluded.

Description

For enrollment into the prospective cohort for Outcome 3.

Inclusion Criteria:

  1. Willing to adhere to the study protocol
  2. Able to provide written consent
  3. English or Spanish speaking
  4. Adult, defined as 18 years or older
  5. Primary reason for presentation to the ED is dyspnea
  6. ED physician is considering a diagnosis of HF, defined by ordering a NP test and/or a chest x-ray

Exclusion Criteria:

  1. History of end-stage renal disease for which hemodialysis is needed
  2. Dyspnea due to primary presentation of an acute coronary syndrome or trauma

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

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Aim 1/Outcome 1
Secondary analysis of frozen plasma samples from the existing STRATIFY cohort of patients with and without acute heart failure presenting to emergency departments. n= ~900
Aim2/Outcome 2
Secondary analysis of frozen plasma samples from the existing EMROC cohort of patients with and without acute heart failure presenting to emergency departments. n= ~900
Aim 3/Outcome 3
Prospective recruitment of approximately 1000 patients with and w/o acute heart failure presenting to emergency departments.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Biomarker Discovery
Time Frame: Enrollment
Define the multi-marker panel of 21 proteins that may improve diagnostic accuracy for acute heart failure
Enrollment
Model derivation for diagnosing acute HF
Time Frame: Enrollment
derive a model for diagnosing acute HF incorporating the 21-biomarker panel from outcome 1
Enrollment
Model validation for diagnosing acute HF
Time Frame: Enrollment
test performance of the multi-marker model (from outcome 2) in a prospective validation cohort
Enrollment

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Vanderbilt University Medical Center

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Wayne State University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Deepak Gupta, MD, MSCI, Vanderbilt University Medical Center

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 (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 31, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 1, 2026

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 1, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 4, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 12, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 13, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 6, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 1, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 210941

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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