Acute Congestive Heart FailureCRUCiALNCT03345446
Circulating RNAs in Acute Congestive Heart Failure
An observational study of Acute Congestive Heart Failure and Heart Failure With Reduced Ejection Fraction, run by Massachusetts General Hospital at 3 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Congestive Heart Failure, Heart Failure With Reduced Ejection Fraction, Heart Failure With Normal Ejection Fraction
- What is being tested?
- Cardiac MRI
- Type of treatment
- Injection or infusion
- How many people
- 200 participants
- Where
- 3 sitesUnited States
- Study dates
- 17 Aug 2016to 31 Dec 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- Age >/= 18 years of age
- Assessment of LV function within the last year or planned during hospital admission
- Acute CHF diagnosis, requiring clinical signs and/or symptoms (including exertional or rest dyspnea, orthopnea or PND) AND
- N-terminal pro-BNP level > 1000 pg/ml or BNP > 400 pg/ml, OR
- Clinical evidence of congestion:
- X-ray evidence of pulmonary edema or pleural effusions
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- 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)
- Clinical response to IV diuretic therapy (as judged by a physician)
Who cannot join
- Hematocrit at time of consent < 30%
- End-stage non-cardiovascular diseases
- Known HIV/AIDS
- Cirrhosis
- Hemodialysis-dependent renal failure
- Pregnancy (as adjudicated by patient history)
Show all 10Show fewer
- Ventricular assist device support
- Acute mechanical support on admission
- Post-heart transplant
- Malignancy within the last 1 year or clinically active rheumatologic or autoimmune illnesses
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
About this study
Official title: 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.
Read the 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:
- What RNAs change in the acute CHF setting, and how do these change over time with diuretic therapy?
- Are these changes in RNA functional? That is, do they cause characteristic changes in the heart in vitro and on heart phenotypes in patients?
- 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:
- Venous blood draw, 40 ml anytime within their hospitalization
- Venous blood draw, 40 ml within 48 hours of planned hospital discharge
- 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).
- Conditions
- Acute Congestive Heart Failure, Heart Failure With Reduced Ejection Fraction, Heart Failure With Normal Ejection Fraction
- Being tested
- Cardiac MRI
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cardiac MRIDiagnostic test
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.
| Study group | Role | What they receive |
|---|---|---|
| Patients with HF-rEF | These patients have Heart Failure with Reduced Ejection Fraction (EF < 55% per the protocol). Receives: Diagnostic Test: Cardiac MRI | |
| Patients with HF-pEF | These patients have Heart Failure with Preserved Ejection Fraction (EF > 55% per the protocol). Receives: Diagnostic Test: Cardiac MRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma RNAs levels (rpm by RNAseq) in patients with acute CHF
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.
Measured: admission vs. decongestion (up to 2 weeks)
Secondary outcomes (1)
Correlation of plasma RNA levels (rpm by RNAseq) with CMR measurements of ventricular function and in vitro fibroblast proliferation assay.
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).
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2017
- Study start17 Aug 2016
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Congestive Heart FailureStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Beth Israel Deaconess Medical Center, Brigham and Women's Hospital, National Heart, Lung, and Blood Institute (NHLBI), American Heart Association
- Responsible party
- Principal investigator, Saumya Das, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03345446
- Sponsor's protocol ID
- 2016P001250
- Other IDs
- 16SFRN29490000, 1K23HL127099-01A1
- Acronym
- CRUCiAL
- Status last verified
- Oct 2025
- First submitted
- 29 Aug 2017
- Last updated
- 23 Oct 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Chatterjee E, Rodosthenous RS, Kujala V, Gokulnath P, Spanos M, Lehmann HI, de Oliveira GP, Shi M, Miller-Fleming TW, Li G, Ghiran IC, Karalis K, Lindenfeld J, Mosley JD, Lau ES, Ho JE, Sheng Q, Shah R, Das S. Circulating extracellular vesicles in human cardiorenal syndrome promote renal injury in a kidney-on-chip system. JCI Insight. 2023 Nov 22;8(22):e165172. doi: 10.1172/jci.insight.165172.
PubMed 37707956
Study at a glance
From the registry record, last updated by the sponsor on 23 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Circulating RNAs in Acute Heart Failure
- ClinicalTrials.gov ID
- NCT03345446
- Acronym / sponsor ID
- CRUCiAL / 2016P001250
- Conditions
- Acute Congestive Heart Failure, Heart Failure With Reduced Ejection Fraction, Heart Failure With Normal Ejection Fraction
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Beth Israel Deaconess Medical Center, Brigham and Women's Hospital, National Heart, Lung, and Blood Institute (NHLBI), American Heart Association
- Study start
- 17 Aug 2016 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 17 Nov 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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:
- What RNAs change in the acute CHF setting, and how do these change over time with diuretic therapy?
- Are these changes in RNA functional? That is, do they cause characteristic changes in the heart in vitro and on heart phenotypes in patients?
- 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:
- Venous blood draw, 40 ml anytime within their hospitalization
- Venous blood draw, 40 ml within 48 hours of planned hospital discharge
- 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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients with HF-rEF | – | Diagnostic Test: Cardiac MRIThese patients have Heart Failure with Reduced Ejection Fraction (EF < 55% per the protocol). |
| Patients with HF-pEF | – | Diagnostic Test: Cardiac MRIThese patients have Heart Failure with Preserved Ejection Fraction (EF > 55% per the protocol). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (9 listed)
- Age >/= 18 years of age
- Assessment of LV function within the last year or planned during hospital admission
- Acute CHF diagnosis, requiring clinical signs and/or symptoms (including exertional or rest dyspnea, orthopnea or PND) AND
- Clinical response to IV diuretic therapy (as judged by a physician)
Key exclusion criteria (10 listed)
- Hematocrit at time of consent < 30%
- End-stage non-cardiovascular diseases
- Pregnancy (as adjudicated by patient history)
- Ventricular assist device support
- Acute mechanical support on admission
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cardiac MRICardiac 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. | Diagnostic test | Patients with HF-pEF, Patients with HF-rEF |
Primary outcome
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.
1 secondary outcome
Correlation of plasma RNA levels (rpm by RNAseq) with CMR measurements of ventricular function and in vitro fibroblast proliferation assay.
Time frame: 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Oct 2025.
- Derived from this study: PubMed 37707956Chatterjee E, Rodosthenous RS, Kujala V, Gokulnath P, Spanos M, Lehmann HI, de Oliveira GP, Shi M, Miller-Fleming TW, Li G, Ghiran IC, Karalis K, Lindenfeld J, Mosley JD, Lau ES, Ho JE, Sheng Q, Shah R, Das S. Circulating extracellular vesicles in human cardiorenal syndrome promote renal injury in a kidney-on-chip system. JCI Insight. 2023 Nov 22;8(22):e165172. doi: 10.1172/jci.insight.165172.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Acute Congestive Heart Failure and Heart Failure With Reduced Ejection Fraction, run by Massachusetts General Hospital at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 23 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Plasma RNAs levels (rpm by RNAseq) in patients with acute CHF (time frame: admission vs. decongestion (up to 2 weeks)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03345446, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Oct 2025.