B-lines Lung Ultrasound Guided ED Management of Acute Heart Failure Pilot Trial (BLUSHED-AHF)

• ClinicalTrials.gov Identifier: NCT03136198
• Recruitment Status: Completed
• First Posted: May 2, 2017
• Results First Posted: May 20, 2020
• Last Update Posted: June 2, 2020
• Sponsor: Indiana University
• Collaborators: Inova Fairfax Hospital; Vanderbilt University; Case Western Reserve University; Wayne State University
• Information provided by (Responsible Party): PETER S PANG, Indiana University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Heart Failure; Heart Failure Acute; Acute Cardiac Pulmonary Edema; Acute Cardiac Failure	Other: LUS-guided strategy-of-care; Other: Usual Care; Drug: Intravenous Loop Diuretic; Drug: Vasodilator; Device: Non invasive Ventilation (NIV)	Phase 2

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

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 130 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Care Provider, Investigator)
• Masking Description: A central, independent, Core Lab will review all images.
• Primary Purpose: Treatment
• Official Title: B-lines Lung Ultrasound Guided ED Management of Acute Heart Failure Pilot Trial
• Actual Study Start Date: July 10, 2017
• Actual Primary Completion Date: March 20, 2019
• Actual Study Completion Date: June 20, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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.	Other: 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: 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; Drug: Intravenous Loop Diuretic; IV loop diuretic; Drug: Vasodilator; IV, topical, or SL Vasodilator; Device: Non invasive Ventilation (NIV); Face, mouth, or nasal mask applied to provide positive pressure ventilation
Placebo Comparator: 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.	Other: Usual Care; Patients will receive usual AHF care; Drug: Intravenous Loop Diuretic; IV loop diuretic; Drug: Vasodilator; IV, topical, or SL Vasodilator; Device: Non invasive Ventilation (NIV); Face, mouth, or nasal mask applied to provide positive pressure ventilation

Outcome Measures

Primary Outcome Measures :

1. 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.

Other Outcome Measures:

1. Total Days Alive and Out Of Hospital (DAOOH) [ Time Frame: Up through 90 days, with specific reporting of events through 30 and 90 days ]
   Total days alive and out of hospital through 30 and 90 days post-discharge
2. Association of B-lines at Discharge and 30-day / 90-day Outcomes [ Time Frame: Up through 90 days, with specific reporting of events through 30 and 90 days ]
3. Change in Biomarkers From Presentation to Pre-discharge [ Time Frame: From admission to pre-discharge from the hospital, on average 5 to 7 days. ]
4. Time to Reach B-lines <15 [ Time Frame: Throughout hospitalization, on average 5-7 days ]
5. B Lines < 15 at 24 Hours and at Discharge [ Time Frame: Through the first 24 hours and then prior to discharge, on average 5-7 days after admission ]
6. Composite of 30-day and 90-day All-cause Mortality, Cardiovascular (CV) Re-hospitalizations, and CV Emergency Department (ED) Revisits. [ Time Frame: Up through 90 days, with specific reporting of events through 30 and 90 days ]
   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.
7. All Cause Readmissions, All Cause ED Re-visits [ Time Frame: Up through 90 days, with specific reporting of events through 30 and 90 days ]
   30- day and 90-day
8. Number of Participants With Physical Exam Findings of Heart Failure When Discharge is Compared to Baseline [ Time Frame: From admission throughout hospitalization, usually 5-7 days. ]
   Physical exam includes body weight, peripheral edema, jugular venous distention, pulmonary and cardiac auscultation
9. Count of Pharmacologic Therapies the Patient Received in the ED [ Time Frame: From admission throughout hospitalization, usually 5-7 days. ]
   This is a description of which pharmacologic therapies the patient has received.
10. Count of Pharmacologic and Device Therapies the Patient Received During Hospitalization [ Time Frame: From admission throughout hospitalization, usually 5-7 days. ]
    This is a description of which pharmacologic and device therapies the patient has received.
11. Comparison of LUS Interpretation Within and Between Trained Investigators as Well as the Core Lab [ Time Frame: From admission throughout hospitalization, usually 5-7 days. ]
    Calculation of intra and inter-agreement between investigators and also the Core Lab to determine the reproducibility of LUS
12. Association of Baseline, Discharge, and Change With 30 and 90 Day Outcomes [ Time Frame: Up through 90 days, with specific reporting of events through 30 and 90 days ]

Eligibility Criteria

• Ages Eligible for Study: 21 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Indiana

Eskenazi Health

Indianapolis, Indiana, United States, 46202

IU Health Methodist Hospital

Indianapolis, Indiana, United States, 46202

United States, Michigan

Detroit Receiving Hospital

Detroit, Michigan, United States, 48201

United States, Ohio

Case Western Reserve University

Cleveland, Ohio, United States, 44106

United States, Tennessee

Vanderbilt University

Nashville, Tennessee, United States, 37235

United States, Virginia

INOVA Health System

Fairfax, Virginia, United States, 22042

Sponsors and Collaborators

Indiana University

Inova Fairfax Hospital

Vanderbilt University

Case Western Reserve University

Wayne State University

Investigators

• Principal Investigator: Peter S Pang, MD; Indiana University

  Study Documents (Full-Text)

Documents provided by PETER S PANG, Indiana University:

Informed Consent Form  [PDF] November 8, 2018

Study Protocol and Statistical Analysis Plan  [PDF] January 23, 2018

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

• Responsible Party: PETER S PANG, Associate Professor, Indiana University
• ClinicalTrials.gov Identifier: NCT03136198
• Other Study ID Numbers: 1R34HL136986-01 ( U.S. NIH Grant/Contract )
• First Posted: May 2, 2017
• Results First Posted: May 20, 2020
• Last Update Posted: June 2, 2020
• Last Verified: May 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by PETER S PANG, Indiana University:

Heart Failure; Acute Heart Failure; Pulmonary Edema; Lung ultrasound; Extra vascular lung water; B-lines

Additional relevant MeSH terms:

Pulmonary Edema; Heart Failure; Heart Diseases; Cardiovascular Diseases; Lung Diseases; Respiratory Tract Diseases; Vasodilator Agents; Diuretics; Sodium Potassium Chloride Symporter Inhibitors; Natriuretic Agents; Physiological Effects of Drugs; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action