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| Name | Class |
|---|---|
| Inova Fairfax Hospital | OTHER |
| Vanderbilt University | OTHER |
| Case Western Reserve University | OTHER |
| Wayne State University |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LUS-guided strategy-of-care | Other | 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:
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | During the ED phase of management, usually no more than 6 hours |
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| Measure | Description | Time Frame |
|---|---|---|
| Total Days Alive and Out Of Hospital (DAOOH) | Total days alive and out of hospital through 30 and 90 days post-discharge | Up through 90 days, with specific reporting of events through 30 and 90 days |
| Association of B-lines at Discharge and 30-day / 90-day Outcomes |
Inclusion Criteria:
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:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Peter S Pang, MD | Indiana University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Eskenazi Health | Indianapolis | Indiana | 46202 | United States | ||
| IU Health Methodist Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34246609 | Derived | 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. | |
| 30448355 | Derived | Russell 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | LUS-guided Strategy-of-care | Patients randomized to the lung ultrasound (LUS) strategy of care arm will be treated according to protocol. This protocol only involves therapies used in everyday AHF clinical practice. LUS-guided strategy-of-care: 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:
Intravenous Loop Diuretic: IV loop diuretic Vasodilator: IV, topical, or SL Vasodilator Non invasive Ventilation (NIV): Face, mouth, or nasal mask applied to provide positive pressure ventilation |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 23, 2018 |
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| OTHER |
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A central, independent, Core Lab will review all images.
|
| Usual Care | Other | Patients will receive usual AHF care |
|
| Intravenous Loop Diuretic | Drug | IV loop diuretic |
|
| Vasodilator | Drug | IV, topical, or SL Vasodilator |
|
| Non invasive Ventilation (NIV) | Device | Face, mouth, or nasal mask applied to provide positive pressure ventilation |
|
| Up through 90 days, with specific reporting of events through 30 and 90 days |
| Change in Biomarkers From Presentation to Pre-discharge | From admission to pre-discharge from the hospital, on average 5 to 7 days. |
| Time to Reach B-lines <15 | Throughout hospitalization, on average 5-7 days |
| B Lines < 15 at 24 Hours and at Discharge | Through the first 24 hours and then prior to discharge, on average 5-7 days after admission |
| Composite of 30-day and 90-day All-cause Mortality, Cardiovascular (CV) Re-hospitalizations, and CV Emergency Department (ED) Revisits. | CV endpoints are defined according to the 2014 American College of Cardiology/American Heart Association (ACC/AHA) Key Data Elements and Definitions for Cardiovascular Endpoint Events. | Up through 90 days, with specific reporting of events through 30 and 90 days |
| All Cause Readmissions, All Cause ED Re-visits | 30- day and 90-day | Up through 90 days, with specific reporting of events through 30 and 90 days |
| Number of Participants With Physical Exam Findings of Heart Failure When Discharge is Compared to Baseline | Physical exam includes body weight, peripheral edema, jugular venous distention, pulmonary and cardiac auscultation | From admission throughout hospitalization, usually 5-7 days. |
| Count of Pharmacologic Therapies the Patient Received in the ED | This is a description of which pharmacologic therapies the patient has received. | From admission throughout hospitalization, usually 5-7 days. |
| Count of Pharmacologic and Device Therapies the Patient Received During Hospitalization | This is a description of which pharmacologic and device therapies the patient has received. | From admission throughout hospitalization, usually 5-7 days. |
| Comparison of LUS Interpretation Within and Between Trained Investigators as Well as the Core Lab | Calculation of intra and inter-agreement between investigators and also the Core Lab to determine the reproducibility of LUS | From admission throughout hospitalization, usually 5-7 days. |
| Association of Baseline, Discharge, and Change With 30 and 90 Day Outcomes | Up through 90 days, with specific reporting of events through 30 and 90 days |
| Indianapolis |
| Indiana |
| 46202 |
| United States |
| Detroit Receiving Hospital | Detroit | Michigan | 48201 | United States |
| Case Western Reserve University | Cleveland | Ohio | 44106 | United States |
| Vanderbilt University | Nashville | Tennessee | 37235 | United States |
| INOVA Health System | Fairfax | Virginia | 22042 | United States |
| FG001 | Usual Care | 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. Usual Care: Patients will receive usual AHF care Intravenous Loop Diuretic: IV loop diuretic Vasodilator: IV, topical, or SL Vasodilator Non invasive Ventilation (NIV): Face, mouth, or nasal mask applied to provide positive pressure ventilation |
| COMPLETED |
|
| NOT COMPLETED |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | LUS-guided Strategy-of-care | 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. LUS-guided strategy-of-care: 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:
Intravenous Loop Diuretic: IV loop diuretic Vasodilator: IV, topical, or SL Vasodilator Non invasive Ventilation (NIV): Face, mouth, or nasal mask applied to provide positive pressure ventilation |
| BG001 | Usual Care | 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. Usual Care: Patients will receive usual AHF care Intravenous Loop Diuretic: IV loop diuretic Vasodilator: IV, topical, or SL Vasodilator Non invasive Ventilation (NIV): Face, mouth, or nasal mask applied to provide positive pressure ventilation |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Out of the 130 participants a total of 8 (5 in the LUS-guided strategy of care arm and 3 in the Usual care arm) had a recorded ED discharge time which was prior to the first LUS, leaving 61 participants in each arm to be analyzed for the primary outcome. | Posted | Count of Participants | Participants | During the ED phase of management, usually no more than 6 hours |
|
|
| |||||||||||||||||||||||||||||
| Other Pre-specified | Total Days Alive and Out Of Hospital (DAOOH) | Total days alive and out of hospital through 30 and 90 days post-discharge | Not Posted | Up through 90 days, with specific reporting of events through 30 and 90 days | Participants | ||||||||||||||||||||||||||||||||||
| Other Pre-specified | Association of B-lines at Discharge and 30-day / 90-day Outcomes | Not Posted | Up through 90 days, with specific reporting of events through 30 and 90 days | Participants | |||||||||||||||||||||||||||||||||||
| Other Pre-specified | Change in Biomarkers From Presentation to Pre-discharge | Not Posted | From admission to pre-discharge from the hospital, on average 5 to 7 days. | Participants | |||||||||||||||||||||||||||||||||||
| Other Pre-specified | Time to Reach B-lines <15 | Not Posted | Throughout hospitalization, on average 5-7 days | Participants | |||||||||||||||||||||||||||||||||||
| Other Pre-specified | B Lines < 15 at 24 Hours and at Discharge | Not Posted | Through the first 24 hours and then prior to discharge, on average 5-7 days after admission | Participants | |||||||||||||||||||||||||||||||||||
| Other Pre-specified | Composite of 30-day and 90-day All-cause Mortality, Cardiovascular (CV) Re-hospitalizations, and CV Emergency Department (ED) Revisits. | CV endpoints are defined according to the 2014 American College of Cardiology/American Heart Association (ACC/AHA) Key Data Elements and Definitions for Cardiovascular Endpoint Events. | Not Posted | Up through 90 days, with specific reporting of events through 30 and 90 days | Participants | ||||||||||||||||||||||||||||||||||
| Other Pre-specified | All Cause Readmissions, All Cause ED Re-visits | 30- day and 90-day | Not Posted | Up through 90 days, with specific reporting of events through 30 and 90 days | Participants | ||||||||||||||||||||||||||||||||||
| Other Pre-specified | Number of Participants With Physical Exam Findings of Heart Failure When Discharge is Compared to Baseline | Physical exam includes body weight, peripheral edema, jugular venous distention, pulmonary and cardiac auscultation | Not Posted | From admission throughout hospitalization, usually 5-7 days. | Participants | ||||||||||||||||||||||||||||||||||
| Other Pre-specified | Count of Pharmacologic Therapies the Patient Received in the ED | This is a description of which pharmacologic therapies the patient has received. | Not Posted | From admission throughout hospitalization, usually 5-7 days. | Participants | ||||||||||||||||||||||||||||||||||
| Other Pre-specified | Count of Pharmacologic and Device Therapies the Patient Received During Hospitalization | This is a description of which pharmacologic and device therapies the patient has received. | Not Posted | From admission throughout hospitalization, usually 5-7 days. | Participants | ||||||||||||||||||||||||||||||||||
| Other Pre-specified | Comparison of LUS Interpretation Within and Between Trained Investigators as Well as the Core Lab | Calculation of intra and inter-agreement between investigators and also the Core Lab to determine the reproducibility of LUS | Not Posted | From admission throughout hospitalization, usually 5-7 days. | Participants | ||||||||||||||||||||||||||||||||||
| Other Pre-specified | Association of Baseline, Discharge, and Change With 30 and 90 Day Outcomes | Not Posted | Up through 90 days, with specific reporting of events through 30 and 90 days | Participants |
7 days from consent
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | LUS-guided Strategy-of-care | 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. LUS-guided strategy-of-care: 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:
Intravenous Loop Diuretic: IV loop diuretic Vasodilator: IV, topical, or SL Vasodilator Non invasive Ventilation (NIV): Face, mouth, or nasal mask applied to provide positive pressure ventilation | 0 | 66 | 2 | 66 | 8 | 66 |
| EG001 | Usual Care | 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. Usual Care: Patients will receive usual AHF care Intravenous Loop Diuretic: IV loop diuretic Vasodilator: IV, topical, or SL Vasodilator Non invasive Ventilation (NIV): Face, mouth, or nasal mask applied to provide positive pressure ventilation | 0 | 64 | 2 | 64 | 15 | 64 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| NSTEMI | Cardiac disorders | Non-systematic Assessment |
| ||
| Gross hematuria | Renal and urinary disorders | Non-systematic Assessment |
| ||
| Mitral Regurgitation, severe | Cardiac disorders | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| NSTEMI type 2 | Cardiac disorders | Non-systematic Assessment |
| ||
| Iron deficiency anemia | Blood and lymphatic system disorders | Non-systematic Assessment |
| ||
| MGUS, new diagnosis | Blood and lymphatic system disorders | Non-systematic Assessment |
| ||
| Constipation | Gastrointestinal disorders | Non-systematic Assessment | Subject was re-admitted due to abdominal pain caused by constipation |
| |
| Hyperkalemia | Metabolism and nutrition disorders | Non-systematic Assessment |
| ||
| Acute Kidney Injury | Renal and urinary disorders | Non-systematic Assessment |
| ||
| Hyponatremia | Renal and urinary disorders | Non-systematic Assessment |
| ||
| Hypotension | Vascular disorders | Non-systematic Assessment |
| ||
| Urinary retention | Renal and urinary disorders | Non-systematic Assessment |
| ||
| Hypotension | Renal and urinary disorders | Non-systematic Assessment |
| ||
| Proteinuria | Renal and urinary disorders | Non-systematic Assessment |
| ||
| Pulmonary embolism | Vascular disorders | Non-systematic Assessment | Deep vein thrombosis and pulmonary embolism |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| Hyponatremia | Cardiac disorders | Non-systematic Assessment |
| ||
| Cough | Cardiac disorders | Non-systematic Assessment |
| ||
| Supratherapeutic digoxin level | Cardiac disorders | Non-systematic Assessment |
| ||
| Nonsustained ventricular tachycardia | Cardiac disorders | Non-systematic Assessment |
| ||
| Mural thrombus | Cardiac disorders | Non-systematic Assessment |
| ||
| Mitral valve disease | Cardiac disorders | Non-systematic Assessment |
| ||
| Hypotension | Cardiac disorders | Non-systematic Assessment |
| ||
| Bradycardia | Cardiac disorders | Non-systematic Assessment | Asymptomatic |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Peter S. Pang | Indiana University | 317-880-3900 | ppang@iu.edu |
| May 19, 2020 |
| Prot_SAP_002.pdf |
| ICF | No | No | Yes | Informed Consent Form | Nov 8, 2018 | Jul 1, 2019 | ICF_000.pdf |
| ID | Term |
|---|---|
| D006333 | Heart Failure |
| D011654 | Pulmonary Edema |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| D014665 | Vasodilator Agents |
| D063087 | Noninvasive Ventilation |
| ID | Term |
|---|---|
| D002317 | Cardiovascular Agents |
| D045506 | Therapeutic Uses |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D012121 | Respiration, Artificial |
| D058109 | Airway Management |
| D013812 | Therapeutics |
| D012138 | Respiratory Therapy |
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| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|