Circulating RNAs in Acute Congestive Heart Failure (CRUCiAL)

October 21, 2025 updated by: Saumya Das, Massachusetts General Hospital

Circulating RNAs in Acute Heart Failure

The purpose of this American Heart Association-funded and NIH-funded study is to examine circulating RNAs in the acute CHF setting, how they change with decongestive therapy, and their function in vitro and in vivo.

The investigators are testing the hypothesis that ex-RNA levels change significantly during decongestion therapy and can be used as a marker of those individuals who respond to CHF therapy (in terms of cardiac structure or outcome). Additionally, the translational research design allows the investigators to assay the effects of these RNAs on tissue phenotypes in vitro.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

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.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Nearly 5 million people in the United States have congestive heart failure (CHF). Although medical therapy such as beta-blockers, angiotensin converting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARBs) and aldosterone antagonists has improved prognosis, the overall rate of hospital admissions has continued to rise in the last decade and the mortality for patients with symptomatic heart failure remains worse than the majority of cancers in this country. Accordingly, significant opportunities exist for the improvement in outcomes of patients with CHF, both from a morbidity and mortality standpoint. Such opportunities may lie in the outpatient medical management of patients with CHF. Specifically acute CHF represents a particularly underserved area of CHF care.

In this regard, the investigative group and others have demonstrated the utility of extracellular RNAs (short, 20-22 nucleotide RNA molecules stable in circulation in humans) to predict cardiac structural changes and fibrosis in patients post-myocardial infarction with significant changes in cardiac structure. However, little has been done looking at the acute CHF setting. Specific questions include:

  1. What RNAs change in the acute CHF setting, and how do these change over time with diuretic therapy?
  2. Are these changes in RNA functional? That is, do they cause characteristic changes in the heart in vitro and on heart phenotypes in patients?
  3. Do these RNAs predict outcomes in long-term follow-up?

To answer these questions, the investigators will enroll patients who are currently admitted at MGH or BIDMC with acute CHF. The study protocol involves:

  1. Venous blood draw, 40 ml anytime within their hospitalization
  2. Venous blood draw, 40 ml within 48 hours of planned hospital discharge
  3. Venous blood draw, 40 ml at follow-up (within one year of discharge)

Eligible patients (e.g., absence of standard MRI contraindications, GFR > 40ml/min/1.73m2) will be asked pre-discharge or by telephone contact after discharge about coming in for a cardiac MRI study at any point within one year of discharge to examine cardiac structure/function and fibrosis. MRI imaging will be performed by Partners investigators (Dr. Ravi Shah, Dr. Michael Steigner, Dr. Michael Jerosch-Herold) at the 221 Longwood BRIC Imaging Facility (at the Brigham and Women's Hospital, BWH).

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 (Estimated)

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.
200

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center
      • Boston, Massachusetts, United States, 02115
        • Brigham and Women's Hospital
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital

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

Patients with Acute Congestive Heart Failure, either with preserved ejection fraction (HF-pEF) or reduced ejection fraction (HF-rEF).

The subjects will be enrolled in the acute CHF setting from two sites:

  • Beth Israel Deaconess Medical Center (BIDMC; under direction of Dr. Pablo Pinzon-Quintero, Heart Failure/Transplant Attending Physician)
  • Massachusetts General Hospital (MGH; under direction of Dr. Ravi Shah, Heart Failure/Transplant Attending Physician)

Subjects will be drawn from the inpatient population at both hospitals, admitted with a diagnosis of heart failure.

Description

Inclusion Criteria:

  1. Age >/= 18 years of age
  2. Assessment of LV function within the last year or planned during hospital admission

  3. Acute CHF diagnosis, requiring clinical signs and/or symptoms (including exertional or rest dyspnea, orthopnea or PND) AND

    1. N-terminal pro-BNP level > 1000 pg/ml or BNP > 400 pg/ml, OR

    2. Clinical evidence of congestion:

      • X-ray evidence of pulmonary edema or pleural effusions
      • Elevated JVP, lower extremity edema, or rales on pulmonary examination
      • Right heart catheterization evidence of elevated filling pressures (RA pressure > 10 mmHg; PCWP > 18 mmHg)
  4. Clinical response to IV diuretic therapy (as judged by a physician)

Exclusion Criteria:

  1. Hematocrit at time of consent < 30%

  2. End-stage non-cardiovascular diseases

    1. Known HIV/AIDS
    2. Cirrhosis
    3. Hemodialysis-dependent renal failure
  3. Pregnancy (as adjudicated by patient history)
  4. Ventricular assist device support
  5. Acute mechanical support on admission
  6. Post-heart transplant
  7. Malignancy within the last 1 year or clinically active rheumatologic or autoimmune illnesses

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.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Patients with HF-rEF
These patients have Heart Failure with Reduced Ejection Fraction (EF < 55% per the protocol).
Diagnostic test: Cardiac MRI
Cardiac MRI is a test that allows us to look at how the heart muscle works and the amount of scar tissue in your heart. Screening questions will be asked to make sure that patients are not pregnant, and that they have kidney function tests to confirm that IV contrast used (gadolinium) during the MRI is safe for them.
Patients with HF-pEF
These patients have Heart Failure with Preserved Ejection Fraction (EF > 55% per the protocol).
Diagnostic test: Cardiac MRI
Cardiac MRI is a test that allows us to look at how the heart muscle works and the amount of scar tissue in your heart. Screening questions will be asked to make sure that patients are not pregnant, and that they have kidney function tests to confirm that IV contrast used (gadolinium) during the MRI is safe for them.

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
Plasma RNAs levels (rpm by RNAseq) in patients with acute CHF
Time Frame: admission vs. decongestion (up to 2 weeks)
Identification of plasma RNAs (absolute reads per million) by RNA sequencing in 1 ml of plasma that are greater than 2 fold increased with p value < 0.05.
admission vs. decongestion (up to 2 weeks)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Correlation of plasma RNA levels (rpm by RNAseq) with CMR measurements of ventricular function and in vitro fibroblast proliferation assay.
Time Frame: 6 months
Correlation (by PCA regression models) of candidate plasma RNAs (absolute reads per million) identified in the primary outcome with cardiac MRI phenotypes, including extracellular volume fraction or ECV (unit less), LV ejection fraction (percentage), LV systolic volume (ml) and in vitro fibroblast proliferation by MTT assay (absorbance at 490 nm).
6 months

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Correlation of candidate plasma RNA levels (measured by qRT-PCR in fold change compared to endogenous control RNA) with short-term and long-term combined cardiovascular outcome
Time Frame: 4 years
Correlation of plasma RNA level by sequencing (absolute reads per million) or qRT-PCR (raw CT values, cycle number, or fold change compared to endogenous control, unit-less) with the combined endpoints of mortality, heart failure admissions, or progression to transplantation or LVAD (yes/no) in up to 2-years via review of national death records databases and electronic health care records review.
4 years

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.
Massachusetts General Hospital

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.
National Heart, Lung, and Blood Institute (NHLBI)
Beth Israel Deaconess Medical Center
Brigham and Women's Hospital
American Heart Association

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 (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 17, 2016

Primary Completion (Estimated)

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.
December 31, 2026

Study Completion (Estimated)

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.
December 31, 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).
August 29, 2017

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.
November 15, 2017

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.
November 17, 2017

Study Record Updates

Last Update Posted (Estimated)

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.
October 23, 2025

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.
October 21, 2025

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.
October 1, 2025

More Information

Terms related to this study

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.
  • 2016P001250
  • 16SFRN29490000 (Other Grant/Funding Number: American Heart Association)
  • 1K23HL127099-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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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