B-lines Lung Ultrasound Guided ED Management of Acute Heart Failure Pilot Trial

NCT ID: NCT03136198

Last Updated: 2024-06-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 130 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-07-10
• Study Completion Date: 2019-06-20

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.

Conditions

Heart Failure; Heart Failure Acute; Acute Cardiac Pulmonary Edema; Acute Cardiac Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

LUS-guided strategy-of-care

Intervention Type: 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:

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

Intravenous Loop Diuretic

Intervention Type: DRUG

IV loop diuretic

Vasodilator

Intervention Type: DRUG

IV, topical, or SL Vasodilator

Non invasive Ventilation (NIV)

Intervention Type: DEVICE

Face, mouth, or nasal mask applied to provide positive pressure ventilation

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.

Group Type: PLACEBO_COMPARATOR

Usual Care

Intervention Type: OTHER

Patients will receive usual AHF care

Intravenous Loop Diuretic

Intervention Type: DRUG

IV loop diuretic

Vasodilator

Intervention Type: DRUG

IV, topical, or SL Vasodilator

Non invasive Ventilation (NIV)

Intervention Type: DEVICE

Face, mouth, or nasal mask applied to provide positive pressure ventilation

Interventions

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:

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

Intervention Type: OTHER

Usual Care

Patients will receive usual AHF care

Intervention Type: OTHER

Intravenous Loop Diuretic

IV loop diuretic

Intervention Type: DRUG

Vasodilator

IV, topical, or SL Vasodilator

Intervention Type: DRUG

Non invasive Ventilation (NIV)

Face, mouth, or nasal mask applied to provide positive pressure ventilation

Intervention Type: DEVICE

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

• Minimum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Inova Fairfax Hospital

OTHER

Sponsor Role: collaborator

Vanderbilt University

OTHER

Sponsor Role: collaborator

Case Western Reserve University

OTHER

Sponsor Role: collaborator

Wayne State University

OTHER

Sponsor Role: collaborator

Indiana University

OTHER

Sponsor Role: lead

Responsible Party

PETER S PANG

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Peter S Pang, MD

Role: PRINCIPAL_INVESTIGATOR

Indiana University

Locations

Eskenazi Health

Indianapolis, Indiana, United States

IU Health Methodist Hospital

Indianapolis, Indiana, United States

Detroit Receiving Hospital

Detroit, Michigan, United States

Case Western Reserve University

Cleveland, Ohio, United States

Vanderbilt University

Nashville, Tennessee, United States

INOVA Health System

Fairfax, Virginia, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 34246609 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30448355 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

1R34HL136986-01

Identifier Type: NIH

Identifier Source: org_study_id

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