Clinical trial NCT03136198: B-lines Lung Ultrasound Guided ED Management of Acute Heart Failure Pilot Trial
Official title: B-lines Lung Ultrasound Guided ED Management of Acute Heart Failure Pilot Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Heart Failure
Heart Failure Acute
Acute Cardiac Pulmonary Edema
Acute Cardiac Failure
Keywords: Heart Failure
Acute Heart Failure
Pulmonary Edema
Lung ultrasound
Extra vascular lung water
B-lines
Lead sponsor: Indiana University
Sponsor class: OTHER
Collaborators: name: Inova Fairfax Hospital
name: Vanderbilt University
name: Case Western Reserve University
name: Wayne State University
First posted: 2017-05-02
Enrollment: 130
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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. 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.

Eligibility criteria: 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:

  * Chest radiograph consistent with AHF
  * Jugular venous distension
  * Pulmonary rales on auscultation
  * Lower extremity edema

Exclusion Criteria:

* 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
* 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

Primary outcomes:
measure: Number of Participants With B-lines ≤ 15 at the Conclusion of ED AHF Management
timeFrame: During the ED phase of management, usually no more than 6 hours
Secondary outcomes:
Other outcomes:
measure: Total Days Alive and Out Of Hospital (DAOOH)
timeFrame: Up through 90 days, with specific reporting of events through 30 and 90 days
measure: Association of B-lines at Discharge and 30-day / 90-day Outcomes
timeFrame: Up through 90 days, with specific reporting of events through 30 and 90 days
measure: Change in Biomarkers From Presentation to Pre-discharge
timeFrame: From admission to pre-discharge from the hospital, on average 5 to 7 days.
measure: Time to Reach B-lines <15
timeFrame: Throughout hospitalization, on average 5-7 days
measure: B Lines < 15 at 24 Hours and at Discharge
timeFrame: Through the first 24 hours and then prior to discharge, on average 5-7 days after admission
measure: Composite of 30-day and 90-day All-cause Mortality, Cardiovascular (CV) Re-hospitalizations, and CV Emergency Department (ED) Revisits.
timeFrame: Up through 90 days, with specific reporting of events through 30 and 90 days
measure: All Cause Readmissions, All Cause ED Re-visits
timeFrame: Up through 90 days, with specific reporting of events through 30 and 90 days
measure: Number of Participants With Physical Exam Findings of Heart Failure When Discharge is Compared to Baseline
timeFrame: From admission throughout hospitalization, usually 5-7 days.
measure: Count of Pharmacologic Therapies the Patient Received in the ED
timeFrame: From admission throughout hospitalization, usually 5-7 days.
measure: Count of Pharmacologic and Device Therapies the Patient Received During Hospitalization
timeFrame: From admission throughout hospitalization, usually 5-7 days.
measure: Comparison of LUS Interpretation Within and Between Trained Investigators as Well as the Core Lab
timeFrame: From admission throughout hospitalization, usually 5-7 days.
measure: Association of Baseline, Discharge, and Change With 30 and 90 Day Outcomes
timeFrame: Up through 90 days, with specific reporting of events through 30 and 90 days
Locations:
city: Indianapolis
country: United States
facility: Eskenazi Health
state: Indiana
city: Indianapolis
country: United States
facility: IU Health Methodist Hospital
state: Indiana
city: Detroit
country: United States
facility: Detroit Receiving Hospital
state: Michigan
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Fairfax
country: United States
facility: INOVA Health System
state: Virginia
Study officials:
affiliation: Indiana University
name: Peter S Pang, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.