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

Heart Failure Clinical Trial

— BLUSHED-AHF  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03136198
• Other study ID #: 1R34HL136986-01
• Status: Completed
• Phase: Phase 2
• Start date: July 10, 2017
• Est. completion date: June 20, 2019

Study information

• Verified date: May 2020
• Source: Indiana University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 130
• Est. completion date: June 20, 2019
• Est. primary completion date: March 20, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Cardiac Failure
• Acute Cardiac Pulmonary Edema
• Heart Failure
• Heart Failure Acute
• Pulmonary Edema

Intervention

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
• Usual Care
Patients will receive usual AHF care

Drug:
• Intravenous Loop Diuretic
IV loop diuretic
• Vasodilator
IV, topical, or SL Vasodilator

Device:
• Non invasive Ventilation (NIV)
Face, mouth, or nasal mask applied to provide positive pressure ventilation

Locations

Country	Name	City	State
United States	Case Western Reserve University	Cleveland	Ohio
United States	Detroit Receiving Hospital	Detroit	Michigan
United States	INOVA Health System	Fairfax	Virginia
United States	Eskenazi Health	Indianapolis	Indiana
United States	IU Health Methodist Hospital	Indianapolis	Indiana
United States	Vanderbilt University	Nashville	Tennessee

Sponsors (5)

Lead Sponsor	Collaborator
Indiana University	Case Western Reserve University, Inova Fairfax Hospital, Vanderbilt University, Wayne State University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	Association of B-lines at Discharge and 30-day / 90-day Outcomes		Up through 90 days, with specific reporting of events through 30 and 90 days
Other	Change in Biomarkers From Presentation to Pre-discharge		From admission to pre-discharge from the hospital, on average 5 to 7 days.
Other	Time to Reach B-lines <15		Throughout hospitalization, on average 5-7 days
Other	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
Other	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
Other	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
Other	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.
Other	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.
Other	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.
Other	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.
Other	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
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.	During the ED phase of management, usually no more than 6 hours