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

• Sponsor: Indiana University (Other)
• Overall Status: Completed
• CT.gov ID: NCT03136198
• Collaborator: Inova Fairfax Hospital (Other), Vanderbilt University (Other), Case Western Reserve University (Other), Wayne State University (Other)
• Enrollment: 130
• Locations: 6
• Arms: 2
• Actual Duration (Months): 23.3
• Patients Per Site: 21.7
• Patients Per Site Per Month: 0.9

Study Details

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
• 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: Jul 10, 2017
• Actual Primary Completion Date: Mar 20, 2019
• Actual Study Completion Date: Jun 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 [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) [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 [Up through 90 days, with specific reporting of events through 30 and 90 days]

3. Change in Biomarkers From Presentation to Pre-discharge [From admission to pre-discharge from the hospital, on average 5 to 7 days.]

4. Time to Reach B-lines <15 [Throughout hospitalization, on average 5-7 days]

5. 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]

6. Composite of 30-day and 90-day All-cause Mortality, Cardiovascular (CV) Re-hospitalizations, and CV Emergency Department (ED) Revisits. [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 [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 [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 [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 [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 [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 [Up through 90 days, with specific reporting of events through 30 and 90 days]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

	Site	City	State	Country	Postal Code
1	Eskenazi Health	Indianapolis	Indiana	United States	46202
2	IU Health Methodist Hospital	Indianapolis	Indiana	United States	46202
3	Detroit Receiving Hospital	Detroit	Michigan	United States	48201
4	Case Western Reserve University	Cleveland	Ohio	United States	44106
5	Vanderbilt University	Nashville	Tennessee	United States	37235
6	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)

• Informed Consent Form - Nov 8, 2018
• Study Protocol and Statistical Analysis Plan - Jan 23, 2018

More Information

Publications

None provided.

• Responsible Party: PETER S PANG, Associate Professor, Indiana University
• ClinicalTrials.gov Identifier: NCT03136198
• Other Study ID Numbers: 1R34HL136986-01
• First Posted: May 2, 2017
• Last Update Posted: Jun 2, 2020
• Last Verified: May 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• 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, Associate Professor, 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; Vasodilator Agents; Diuretics; Sodium Potassium Chloride Symporter Inhibitors

Study Results

Participant Flow

Arm/Group Title	LUS-guided Strategy-of-care	Usual Care
Arm/Group Description	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: 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 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	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
Period Title: Overall Study
STARTED	66	64
COMPLETED	66	63
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	LUS-guided Strategy-of-care	Usual Care	Total
Arm/Group Description	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: 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 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	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	Total of all reporting groups
Overall Participants	66	64	130
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.8 (15.9)	66.2 (12.2)	65.0 (14.2)
Sex: Female, Male (Count of Participants)
Female	19 28.8%	18 28.1%	37 28.5%
Male	47 71.2%	46 71.9%	93 71.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 3%	1 1.6%	3 2.3%
Not Hispanic or Latino	63 95.5%	61 95.3%	124 95.4%
Unknown or Not Reported	1 1.5%	2 3.1%	3 2.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	35 53%	34 53.1%	69 53.1%
White	30 45.5%	29 45.3%	59 45.4%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 1.5%	1 1.6%	2 1.5%
Region of Enrollment (participants) [Number]
United States	66 100%	64 100%	130 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With B-lines ≤ 15 at the Conclusion of ED AHF Management
Description	B-lines ≤ 15 at the conclusion of ED AHF management or maximum of 6 hours after enrollment, whichever comes first.
Time Frame	During the ED phase of management, usually no more than 6 hours

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	LUS-guided Strategy-of-care	Usual Care
Arm/Group Description	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: 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 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	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
Measure Participants	61	61
Count of Participants [Participants]	7 10.6%	10 15.6%

2. Other Pre-specified Outcome

Title	Total Days Alive and Out Of Hospital (DAOOH)
Description	Total days alive and out of hospital through 30 and 90 days post-discharge
Time Frame	Up through 90 days, with specific reporting of events through 30 and 90 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Other Pre-specified Outcome

Title	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Other Pre-specified Outcome

Title	Change in Biomarkers From Presentation to Pre-discharge
Time Frame	From admission to pre-discharge from the hospital, on average 5 to 7 days.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Other Pre-specified Outcome

Title	Time to Reach B-lines <15
Time Frame	Throughout hospitalization, on average 5-7 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Other Pre-specified Outcome

Title	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Other Pre-specified Outcome

Title	Composite of 30-day and 90-day All-cause Mortality, Cardiovascular (CV) Re-hospitalizations, and CV Emergency Department (ED) Revisits.
Description	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.
Time Frame	Up through 90 days, with specific reporting of events through 30 and 90 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Other Pre-specified Outcome

Title	All Cause Readmissions, All Cause ED Re-visits
Description	30- day and 90-day
Time Frame	Up through 90 days, with specific reporting of events through 30 and 90 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

9. Other Pre-specified Outcome

Title	Number of Participants With Physical Exam Findings of Heart Failure When Discharge is Compared to Baseline
Description	Physical exam includes body weight, peripheral edema, jugular venous distention, pulmonary and cardiac auscultation
Time Frame	From admission throughout hospitalization, usually 5-7 days.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

10. Other Pre-specified Outcome

Title	Count of Pharmacologic Therapies the Patient Received in the ED
Description	This is a description of which pharmacologic therapies the patient has received.
Time Frame	From admission throughout hospitalization, usually 5-7 days.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

11. Other Pre-specified Outcome

Title	Count of Pharmacologic and Device Therapies the Patient Received During Hospitalization
Description	This is a description of which pharmacologic and device therapies the patient has received.
Time Frame	From admission throughout hospitalization, usually 5-7 days.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

12. Other Pre-specified Outcome

Title	Comparison of LUS Interpretation Within and Between Trained Investigators as Well as the Core Lab
Description	Calculation of intra and inter-agreement between investigators and also the Core Lab to determine the reproducibility of LUS
Time Frame	From admission throughout hospitalization, usually 5-7 days.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

13. Other Pre-specified Outcome

Title	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	7 days from consent
Arm/Group Title	LUS-guided Strategy-of-care		Usual Care
Arm/Group Description	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: 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 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		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
All Cause Mortality
	LUS-guided Strategy-of-care		Usual Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/66 (1.5%)		0/63 (0%)
Serious Adverse Events
	LUS-guided Strategy-of-care		Usual Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/66 (3%)		2/63 (3.2%)
Cardiac disorders
NSTEMI	1/66 (1.5%)	1	1/63 (1.6%)	1
Mitral Regurgitation, severe	0/66 (0%)	0	1/63 (1.6%)	1
Renal and urinary disorders
Gross hematuria	1/66 (1.5%)	1	0/63 (0%)	0
Other (Not Including Serious) Adverse Events
	LUS-guided Strategy-of-care		Usual Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/66 (12.1%)		15/63 (23.8%)
Blood and lymphatic system disorders
Iron deficiency anemia	0/66 (0%)	0	1/63 (1.6%)	1
MGUS, new diagnosis	0/66 (0%)	0	1/63 (1.6%)	1
Cardiac disorders
NSTEMI type 2	0/66 (0%)	0	5/63 (7.9%)	5
Hyponatremia	1/66 (1.5%)	1	0/63 (0%)	0
Cough	1/66 (1.5%)	1	0/63 (0%)	0
Supratherapeutic digoxin level	1/66 (1.5%)	1	0/63 (0%)	0
Nonsustained ventricular tachycardia	1/66 (1.5%)	1	1/63 (1.6%)	1
Mural thrombus	0/66 (0%)	0	1/63 (1.6%)	1
Mitral valve disease	0/66 (0%)	0	1/63 (1.6%)	1
Hypotension	0/66 (0%)	0	1/63 (1.6%)	1
Bradycardia	0/66 (0%)	0	1/63 (1.6%)	1
Gastrointestinal disorders
Constipation	1/66 (1.5%)	1	0/63 (0%)	0
Metabolism and nutrition disorders
Hyperkalemia	0/66 (0%)	0	1/63 (1.6%)	1
Renal and urinary disorders
Acute Kidney Injury	4/66 (6.1%)	4	4/63 (6.3%)	4
Hyponatremia	1/66 (1.5%)	1	0/63 (0%)	0
Urinary retention	0/66 (0%)	0	1/63 (1.6%)	1
Hypotension	0/66 (0%)	0	1/63 (1.6%)	1
Proteinuria	0/66 (0%)	0	1/63 (1.6%)	1
Respiratory, thoracic and mediastinal disorders
Respiratory failure	0/66 (0%)	0	2/63 (3.2%)	2
Vascular disorders
Hypotension	1/66 (1.5%)	1	0/63 (0%)	0
Pulmonary embolism	0/66 (0%)	0	1/63 (1.6%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.