Heart FailurePhase 2BLUSHED-AHFNCT03136198
B-lines Lung Ultrasound Guided ED Management of Acute Heart Failure Pilot Trial
A Phase 2 study testing LUS-guided strategy-of-care, Intravenous Loop Diuretic and Vasodilator in people with Heart Failure and Heart Failure Acute, run by Indiana University at 6 sites in United States.
Trial summary
Nearly 80% of acute heart failure (AHF) patients admitted to the hospital are initially treated in the emergency department (ED). Once admitted, within 30 days post-discharge, 27% of patients are re-hospitalized or die. Attempts to improve outcomes with novel therapies have all failed. Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Heart Failure, Heart Failure Acute, Acute Cardiac Pulmonary Edema
- What is being tested?
- LUS-guided strategy-of-care, Intravenous Loop Diuretic and Vasodilator
- Type of treatment
- Pill or oral medicine, Injection or infusion, Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 130 participants
- Where
- 6 sitesUnited States
- Study dates
- 10 Jul 2017to 20 Jun 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 21 years
- Presents with shortness of breath at rest or with minimal exertion
- Clinical diagnosis of AHF and presence of > 15 total bilateral B-lines distributed in at least 4 zones on initial LUS
- Hx of chronic HF and any one of the following:
- Chest radiograph consistent with AHF
- Jugular venous distension
- Pulmonary rales on auscultation
- Lower extremity edema
Who cannot join
- Chronic renal dysfunction, including end-stage renal disease (ESRD) or estimated glomerular filtration rate (eGFR) < 45ml//min/1.73m2.
- Shock of any kind. Any requirement for vasopressors or inotropes.
- Systolic blood pressure (SBP) < 100 or >175 mmHg
- Need for immediate intubation
- Acute Coronary Syndrome- Presentation consistent with myocardial ischemia AND either new ST-segment elevation/depression
- Fever >101.5 ºF or chest radiograph or clinical picture of pneumonia
Show all 11Show fewer
- End stage HF: transplant list, ventricular assist device
- Anemia requiring transfusion
- Known interstitial lung disease
- Suspected acute lung injury or acute respiratory distress syndrome (ARDS)
- Pregnant or recently pregnant within the last 6 months
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Case Western Reserve University
Cleveland, Ohio, 44106
Detroit Receiving Hospital
Detroit, Michigan, 48201
INOVA Health System
Fairfax, Virginia, 22042
Eskenazi Health
Indianapolis, Indiana, 46202
IU Health Methodist Hospital
Indianapolis, Indiana, 46202
Vanderbilt University
Nashville, Tennessee, 37235
About this study
Nearly 80% of acute heart failure (AHF) patients admitted to the hospital are initially treated in the emergency department (ED). Once admitted, within 30 days post-discharge, 27% of patients are re-hospitalized or die. Attempts to improve outcomes with novel therapies have all failed. The evidence for existing AHF therapies are poor: No currently used AHF treatment is known to improve outcomes. ED treatment is largely the same today as 40 years ago. Congestion, such as difficulty breathing, weight gain, and leg swelling, is the primary reason why patients present to the hospital for AHF. Treating congestion is the cornerstone of AHF management. Yet half of all AHF patients leave the hospital inadequately decongested. The investigators propose a novel approach to aggressively decongest patients in the ED setting: lung ultrasound guided, protocol driven, AHF management. LUS B-lines are a measure of extra-vascular lung water (EVLW). In the setting of AHF, LUS B-lines are a measure of congestion. This simple, easily learned technique has excellent reliability and reproducibility. The investigators hypothesize that a strategy-of-care will outperform usual care. At the present time, usual care is largely empirical. This study will improve the evidence base for ED AHF management. This proposed pilot study, if successful, will lead to an outcome trial examining whether an ED AHF strategy-of-care increases days alive and out of the hospital for patients.
Read the detailed description
The primary goal of the BLUSHED AHF pilot trial is to determine whether an early lung ultrasound (LUS) guided, protocol-driven ED AHF strategy-of-care leads to more rapid and sustained resolution of congestion, as measured by LUS B-lines. If the investigators are able to demonstrate this necessary and sufficient information - targeted strategy-of-care is more effective than usual care - they will apply for a follow on study to achieve the following aim.
Aim 1: To demonstrate the effectiveness of a targeted decongestion strategy - LUS guided, protocol-driven ED AHF management - will result in improved 30-day outcomes vs. usual care. This aim will be tested using a randomized, controlled, unblinded, pragmatic, multi-center, simple trial design.
The pilot trial may determine that ED management alone is insufficient to impact the outcome. Thus, the investigators may need to modify their subsequent trial design to include targeted therapy throughout hospitalization. However, the pilot study will demonstrate whether targeted therapy effectively reduces B-lines.
PUBLIC HEALTH IMPACT Over one million hospitalizations for AHF occur every year in the US. Within 30 days after hospitalization, over 25% of AHF patients will be dead or re-hospitalized.4 Up to 67% of patients will be re-hospitalized and 36% will be dead by one year. For patients aged 65 years and older, AHF is the most common and most expensive reason for hospitalization. Despite major reductions in morbidity and mortality for chronic HF, considerably less progress has been seen in AHF.
Congestion is the primary reason why AHF patients present to the ED seeking medical care. Congestion is manifest by signs and symptoms of heart failure (HF); dyspnea, orthopnea, edema, and weight gain. Yet, how to best assess, grade, and manage congestion is not well established.
Freedom from congestion is associated with improved outcomes; Yet many patients leave the hospital inadequately decongested. The absence of robust, reliable methods to assess congestion is a primary reason why it is not well-assessed. A recent consensus statement published in 2010 highlights this fact: "…no method to assess congestion…has been validated." The investigators would argue many ED AHF patients are poorly assessed prior to treatment. In addition, they are poorly re-assessed prior to hospitalization to gauge the success or failure of initial management. While physical exam is currently the cornerstone of congestion assessment, it lacks sensitivity and inter-rater reliability.
The investigators challenge the current paradigm of relying on insensitive methods of congestion to guide therapy. Furthermore, they argue the lack of a robust evidence base for ED management of congestion contributes to poor outcomes.
- Being tested
- LUS-guided strategy-of-care, Usual Care, Intravenous Loop Diuretic, Vasodilator, Non invasive Ventilation (NIV)
- Keywords
- Heart Failure, Acute Heart Failure, Pulmonary Edema, Lung ultrasound, Extra vascular lung water, B-lines
- Medical subject headings
- Heart Failure, Pulmonary Edema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LUS-guided strategy-of-careOther
For patients randomized to the strategy-of-care arm, the LUS guided protocol will be initiated and continued until there is a decrease in B-lines to ≤ 15 or 6 hours of care has been delivered, whichever comes first.
Treatment protocol:
- IV furosemide (unless already given): 2x single oral dose if on chronic therapy or 20-40 mg if diuretic naive.
- Optional therapies: non-invasive ventilation, vasodilators (SL, topical, or IV)
- Reassessment every 2 hours
Usual CareOther
Patients will receive usual AHF care
Intravenous Loop DiureticDrug
IV loop diuretic
VasodilatorDrug
IV, topical, or SL Vasodilator
Non invasive Ventilation (NIV)Device
Face, mouth, or nasal mask applied to provide positive pressure ventilation
| Study group | Role | What they receive |
|---|---|---|
| LUS-guided strategy-of-care | Experimental | Patients randomized to the LUS strategy of care arm will be treated according to protocol. This protocol only involves therapies used in everyday AHF clinical practice. Receives: Other: LUS-guided strategy-of-care; Drug: Intravenous Loop Diuretic; Drug: Vasodilator; Device: Non invasive Ventilation (NIV) |
| Usual care | Placebo comparator | Patients randomized to the usual care arm will also undergo lung ultrasound assessments. However, these results will not be revealed to the care team. Patients will receive treatment per usual, standard care. Receives: Other: Usual Care; Drug: Intravenous Loop Diuretic; Drug: Vasodilator; Device: Non invasive Ventilation (NIV) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With B-lines ≤ 15 at the Conclusion of ED AHF Management
B-lines ≤ 15 at the conclusion of ED AHF management or maximum of 6 hours after enrollment, whichever comes first.
Measured: During the ED phase of management, usually no more than 6 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 May 2017
- Study start10 Jul 2017
- Primary completion20 Mar 2019
- Study completion20 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- More trials run by Indiana UniversityThe 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Care provider, Investigator
- Enrolment
- 130 participants (actual)
Sponsor and investigators
- Lead sponsor
- Indiana University
- Sponsor type
- University, hospital or other
- Collaborators
- Inova Fairfax Hospital, Vanderbilt University, Case Western Reserve University, Wayne State University
- Responsible party
- Principal investigator, PETER S PANG, Indiana University
- Investigators
- Peter S Pang, MD, Principal investigator, Indiana University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03136198
- Sponsor's protocol ID
- 1R34HL136986-01
- Acronym
- BLUSHED-AHF
- Status last verified
- Jun 2024
- First submitted
- 19 Apr 2017
- Last updated
- 4 Jun 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Pang PS, Russell FM, Ehrman R, Ferre R, Gargani L, Levy PD, Noble V, Lane KA, Li X, Collins SP. Lung Ultrasound-Guided Emergency Department Management of Acute Heart Failure (BLUSHED-AHF): A Randomized Controlled Pilot Trial. JACC Heart Fail. 2021 Sep;9(9):638-648. doi: 10.1016/j.jchf.2021.05.008. Epub 2021 Jul 7.
PubMed 34246609Russell FM, Ehrman RR, Ferre R, Gargani L, Noble V, Rupp J, Collins SP, Hunter B, Lane KA, Levy P, Li X, O'Connor C, Pang PS. Design and rationale of the B-lines lung ultrasound guided emergency department management of acute heart failure (BLUSHED-AHF) pilot trial. Heart Lung. 2019 May-Jun;48(3):186-192. doi: 10.1016/j.hrtlng.2018.10.027. Epub 2018 Nov 15.
PubMed 30448355
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- B-lines Lung Ultrasound Guided ED Management of Acute Heart Failure Pilot Trial
- ClinicalTrials.gov ID
- NCT03136198
- Acronym / sponsor ID
- BLUSHED-AHF / 1R34HL136986-01
- Keywords
- Heart Failure, Acute Heart Failure, Pulmonary Edema, Lung ultrasound, Extra vascular lung water, B-lines
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 130 participants (actual)
- Lead sponsor
- Indiana UniversityUniversity, hospital or other
- Collaborators
- Inova Fairfax Hospital, Vanderbilt University, Case Western Reserve University, Wayne State University
- Study start
- 10 Jul 2017 (actual)
- Primary completion
- 20 Mar 2019 (actual)
- Study completion
- 20 Jun 2019 (actual)
- First posted
- 2 May 2017 (actual)
- Results
- Posted 20 May 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Nearly 80% of acute heart failure (AHF) patients admitted to the hospital are initially treated in the emergency department (ED). Once admitted, within 30 days post-discharge, 27% of patients are re-hospitalized or die. Attempts to improve outcomes with novel therapies have all failed. The evidence for existing AHF therapies are poor: No currently used AHF treatment is known to improve outcomes. ED treatment is largely the same today as 40 years ago. Congestion, such as difficulty breathing, weight gain, and leg swelling, is the primary reason why patients present to the hospital for AHF. Treating congestion is the cornerstone of AHF management. Yet half of all AHF patients leave the hospital inadequately decongested. The investigators propose a novel approach to aggressively decongest patients in the ED setting: lung ultrasound guided, protocol driven, AHF management. LUS B-lines are a measure of extra-vascular lung water (EVLW). In the setting of AHF, LUS B-lines are a measure of congestion. This simple, easily learned technique has excellent reliability and reproducibility. The investigators hypothesize that a strategy-of-care will outperform usual care. At the present time, usual care is largely empirical. This study will improve the evidence base for ED AHF management. This proposed pilot study, if successful, will lead to an outcome trial examining whether an ED AHF strategy-of-care increases days alive and out of the hospital for patients.
Detailed description
The primary goal of the BLUSHED AHF pilot trial is to determine whether an early lung ultrasound (LUS) guided, protocol-driven ED AHF strategy-of-care leads to more rapid and sustained resolution of congestion, as measured by LUS B-lines. If the investigators are able to demonstrate this necessary and sufficient information - targeted strategy-of-care is more effective than usual care - they will apply for a follow on study to achieve the following aim.
Aim 1: To demonstrate the effectiveness of a targeted decongestion strategy - LUS guided, protocol-driven ED AHF management - will result in improved 30-day outcomes vs. usual care. This aim will be tested using a randomized, controlled, unblinded, pragmatic, multi-center, simple trial design.
The pilot trial may determine that ED management alone is insufficient to impact the outcome. Thus, the investigators may need to modify their subsequent trial design to include targeted therapy throughout hospitalization. However, the pilot study will demonstrate whether targeted therapy effectively reduces B-lines.
PUBLIC HEALTH IMPACT Over one million hospitalizations for AHF occur every year in the US. Within 30 days after hospitalization, over 25% of AHF patients will be dead or re-hospitalized.4 Up to 67% of patients will be re-hospitalized and 36% will be dead by one year. For patients aged 65 years and older, AHF is the most common and most expensive reason for hospitalization. Despite major reductions in morbidity and mortality for chronic HF, considerably less progress has been seen in AHF.
Congestion is the primary reason why AHF patients present to the ED seeking medical care. Congestion is manifest by signs and symptoms of heart failure (HF); dyspnea, orthopnea, edema, and weight gain. Yet, how to best assess, grade, and manage congestion is not well established.
Freedom from congestion is associated with improved outcomes; Yet many patients leave the hospital inadequately decongested. The absence of robust, reliable methods to assess congestion is a primary reason why it is not well-assessed. A recent consensus statement published in 2010 highlights this fact: "…no method to assess congestion…has been validated." The investigators would argue many ED AHF patients are poorly assessed prior to treatment. In addition, they are poorly re-assessed prior to hospitalization to gauge the success or failure of initial management. While physical exam is currently the cornerstone of congestion assessment, it lacks sensitivity and inter-rater reliability.
The investigators challenge the current paradigm of relying on insensitive methods of congestion to guide therapy. Furthermore, they argue the lack of a robust evidence base for ED management of congestion contributes to poor outcomes.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LUS-guided strategy-of-care | Experimental | Other: LUS-guided strategy-of-care, Drug: Intravenous Loop Diuretic, Drug: Vasodilator, Device: Non invasive Ventilation (NIV)Patients randomized to the LUS strategy of care arm will be treated according to protocol. This protocol only involves therapies used in everyday AHF clinical practice. |
| Usual care | Placebo comparator | Other: Usual Care, Drug: Intravenous Loop Diuretic, Drug: Vasodilator, Device: Non invasive Ventilation (NIV)Patients randomized to the usual care arm will also undergo lung ultrasound assessments. However, these results will not be revealed to the care team. Patients will receive treatment per usual, standard care. |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age ≥ 21 years
- Presents with shortness of breath at rest or with minimal exertion
- Clinical diagnosis of AHF and presence of > 15 total bilateral B-lines distributed in at least 4 zones on initial LUS
- Hx of chronic HF and any one of the following:
Key exclusion criteria (11 listed)
- Chronic renal dysfunction, including end-stage renal disease (ESRD) or estimated glomerular filtration rate (eGFR) < 45ml//min/1.73m2.
- Shock of any kind. Any requirement for vasopressors or inotropes.
- Systolic blood pressure (SBP) < 100 or >175 mmHg
- Need for immediate intubation
- Acute Coronary Syndrome- Presentation consistent with myocardial ischemia AND either new ST-segment elevation/depression
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 |
|---|---|---|
| LUS-guided strategy-of-careFor patients randomized to the strategy-of-care arm, the LUS guided protocol will be initiated and continued until there is a decrease in B-lines to ≤ 15 or 6 hours of care has been delivered, whichever comes first. Treatment protocol: 1. IV furosemide (unless already given): 2x single oral dose if on chronic therapy or 20-40 mg if diuretic naive. 2. Optional therapies: non-invasive ventilation, vasodilators (SL, topical, or IV) 3. Reassessment every 2 hours | Other | LUS-guided strategy-of-care |
| Usual CarePatients will receive usual AHF care | Other | Usual care |
| Intravenous Loop DiureticIV loop diuretic | Drug | LUS-guided strategy-of-care, Usual care |
| VasodilatorIV, topical, or SL Vasodilator | Drug | LUS-guided strategy-of-care, Usual care |
| Non invasive Ventilation (NIV)Face, mouth, or nasal mask applied to provide positive pressure ventilation | Device | LUS-guided strategy-of-care, Usual care |
Primary outcome
Number of Participants With B-lines ≤ 15 at the Conclusion of ED AHF Management
Time frame: During the ED phase of management, usually no more than 6 hours
B-lines ≤ 15 at the conclusion of ED AHF management or maximum of 6 hours after enrollment, whichever comes first.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34246609Pang PS, Russell FM, Ehrman R, Ferre R, Gargani L, Levy PD, Noble V, Lane KA, Li X, Collins SP. Lung Ultrasound-Guided Emergency Department Management of Acute Heart Failure (BLUSHED-AHF): A Randomized Controlled Pilot Trial. JACC Heart Fail. 2021 Sep;9(9):638-648. doi: 10.1016/j.jchf.2021.05.008. Epub 2021 Jul 7.
- Derived from this study: PubMed 30448355Russell FM, Ehrman RR, Ferre R, Gargani L, Noble V, Rupp J, Collins SP, Hunter B, Lane KA, Levy P, Li X, O'Connor C, Pang PS. Design and rationale of the B-lines lung ultrasound guided emergency department management of acute heart failure (BLUSHED-AHF) pilot trial. Heart Lung. 2019 May-Jun;48(3):186-192. doi: 10.1016/j.hrtlng.2018.10.027. Epub 2018 Nov 15.
- 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.
Peter S Pang, MD principal investigator
Indiana University
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing LUS-guided strategy-of-care, Intravenous Loop Diuretic and Vasodilator in people with Heart Failure and Heart Failure Acute, run by Indiana University at 6 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 8 inclusion and 11 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: finished, as of the sponsor's last update on 4 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 May 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With B-lines ≤ 15 at the Conclusion of ED AHF Management (time frame: During the ED phase of management, usually no more than 6 hours). 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 NCT03136198, which also lists 2 linked publications.
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 4 Jun 2024.