Using Short Stay Units Instead of Routine Admission to Improve Patient Centered Health Outcomes for AHF Patients
Phase: NA
Conditions: Acute Heart Failure
Sponsor: Indiana University

ii 
SSU Protocol V6.0 9.20.2019 
Using Short Stay Units Instead of Routine Admission to Improve Patient 
Centered Health Outcomes for AHF Patients  
Principal Investigator: Peter S. Pang MD 
IND/IDE Sponsor: NA 
Funded by: AHRQ 
Version Number:  6.0 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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SSU Protocol V6.0 9.20.2019 
Sept 6, 2017   V3.2   A001 
1. Clarification of eligibility criteria as well as adverse events. 
2. Aug 16: clarified treatment algorithm 
3. 3.0: Clarification of AE’s 
4. Schedule of events table – Typo corrected 
 
Nov 25, 2017   V3.9    A005 
1. Deleted CBQ-HF and added two other Caregiver Burden Scales, 
2. New caregiver scales added to schedule of events at baseline and 30 days. 
3. Removed the Cr(creatinine lab) requirement from the exclusion criteria  and 
4.  excluded patients hospitalized within 30 days of enrollment. 
5. Clarified what data is collected if a patient is hospitalized from the SSU. 
 
Feb 16, 2018    V4.0  A007 
1. Clarified eligibility criteria regarding the 30 day exclusion. 
2. Clarified that patients on baseline oxygen requirement are still eligible. 
3. Endpoint clarification for patients randomized to SSU 
 
Feb 26, 2018 
V4.1 A008 
1. Modified Bakas Caregiving Outcomes Scale 
2. Payment section updated 
 
May 9, 2018       R001 V5.0 
1. Changed Systolic Blood Pressure from >115 to >110 in the inclusion criteria 
2. Addition to inclusion criteria: “That if vital signs improve, the subject can be considered eligible.”  
3. Addition to inclusion criteria: “The last heart rate and systolic blood pressure should be within 1 hour of 
randomization.” 
4. Removed BUN exclusion criteria 
5. Changed Sodium < 135 to Sodium ≤ 131 
 
July 12, 2019     V 6.0 
1.  Changed Systolic Blood Pressure from >110 to >100 in the inclusion criteria.  
2. Removed “Oxygen saturation >93% on room air” from inclusion criteria.  
3. Changed GFR <30 to <20 in exclusion criteria 
4. Removed  “Hemoglobin <9, Sodium ≤ 131, GFR <305. Changed caregiver consenting procedures to include 
verbal consent if acceptable from individual IRBs.  
6. Added repleting potassium to expectedness within Adverse events.  
7. Changed caregiver consent to verbal consent from written informed consent. No medical record review of 
caregiver, purely survey questions. 
 

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SSU Protocol V6.0 9.20.2019 
 
Table of Contents 
LIST OF ABBREVIATIONS ............................................................................................................................... 7 
STATEMENT OF COMPLIANCE ...................................................................................................................... 7 
PROTOCOL SUMMARY .................................................................................................................................. 8 
SCHEMATIC OF STUDY DESIGN ................................................................................................................... 10 
1 
KEY ROLES ........................................................................................................................................ 10 
2  
INTRODUCTION: BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE ............................... 10 
2.1 
Background Information ........................................................................................................ 10 
2.2 
Rationale ................................................................................................................................ 11 
2.3 
Potential Risks and Benefits ................................................................................................... 11 
2.3.1 
Known Potential Risks .......................................................................................... 11 
2.3.2 
Known Potential Benefits .................................................................................... 11 
3 
OBJECTIVES AND PURPOSE.............................................................................................................. 12 
4 
STUDY DESIGN AND ENDPOINTS ..................................................................................................... 12 
4.1 
Description of the Study Design ............................................................................................ 12 
4.2.1 
Primary Endpoint ................................................................................................. 12 
4.2.2 
Exploratory Endpoints.......................................................................................... 12 
5 
STUDY ENROLLMENT AND WITHDRAWAL ...................................................................................... 12 
5.1 
Participant Inclusion Criteria ................................................................................................. 12 
5.2 
Participant Exclusion Criteria ................................................................................................. 12 
5.3 
Strategies for Recruitment and Retention ............................................................................. 13 
5.4 
Participant Withdrawal or termination ................................................................................. 14 
5.4.1 
Reasons for Withdrawal or Termination ............................................................. 14 
5.4.2 
Handling of Participant Withdrawals or termination .......................................... 14 
5.5 
Premature Termination or Suspension of Study ................................................................... 14 
6 
STUDY AGENT .................................................................................................................................. 14 
6.1 
Study Agent(s) and Control Description ................................................................................ 14 
6.1.1 
Dosing & Dose escalation .................................................................................... 14 
6.1.2 
Duration of Therapy ............................................................................................. 16 
7 
STUDY PROCEDURES AND SCHEDULE ............................................................................................. 16 
7.1 
Study Procedures/Evaluations ............................................................................................... 16 
7.1.1 
Study specific procedures .................................................................................... 16 
7.1.2 
Standard of care study procedures ...................................................................... 16 
7.2 
Laboratory Procedures/Evaluations ...................................................................................... 16 
7.2.1 
Clinical Laboratory Evaluations ............................................................................ 16 
7.2.2 
Other Assays or Procedures .................................... Error! Bookmark not defined. 
7.2.3 
Specimen Preparation, Handling, and Storage ....... Error! Bookmark not defined. 
7.2.4 
Specimen Shipment ................................................ Error! Bookmark not defined. 
7.3 
Study Schedule....................................................................................................................... 16 
7.3.1 
Screening ............................................................................................................. 16 
7.3.2 
Enrollment/Baseline ............................................................................................ 17 
7.3.3 
Follow-up & Final study visit ................................................................................ 17 

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SSU Protocol V6.0 9.20.2019 
7.3.7 
Schedule of Events Table ..................................................................................... 18 
7.5 
Concomitant Medications ..................................................................................................... 18 
7.6 
Prohibited Medications, Treatments, and Procedures .......................................................... 19 
8 
ASSESSMENT OF SAFETY.................................................................................................................. 19 
8.1 
Specification of Safety Parameters ........................................................................................ 19 
8.1.1 
Definition of Adverse Events (AE) ........................................................................ 19 
8.1.2 
Definition of Serious Adverse Events (SAE) ......................................................... 19 
8.2 
Classification of an Adverse Event ......................................................................................... 20 
8.2.1 
Severity of Event .................................................................................................. 20 
8.2.2 
Relationship to Study Agent ................................................................................ 20 
8.2.3 
Expectedness ....................................................................................................... 20 
8.3 
Time Period and Frequency for Event Assessment and Follow-Up ....................................... 21 
8.4 
Reporting Procedures ............................................................................................................ 21 
8.4.1 
Adverse Event Reporting ..................................................................................... 21 
8.4.2 
Serious Adverse Event Reporting ......................................................................... 21 
8.5 
Study Halting Rules ................................................................................................................ 21 
8.6 
Safety Oversight ..................................................................................................................... 21 
9 
CLINICAL MONITORING ................................................................................................................... 21 
10 
STATISTICAL CONSIDERATIONS ....................................................................................................... 21 
10.1 
Statistical and Analytical Plans .............................................................................................. 21 
10.2 
Statistical Hypotheses ............................................................................................................ 21 
10.3 
Analysis Datasets ................................................................................................................... 23 
10.4 
Description of Statistical Methods ........................................................................................ 24 
10.4.1 
General Approach ................................................................................................ 24 
10.4.2 
Analysis of the Primary Efficacy Endpoint(s) ....................................................... 24 
10.4.3 
Analysis of the EXPLORATORY Endpoint(s) .......................................................... 24 
10.4.4 
Safety Analyses .................................................................................................... 29 
10.4.5 
Adherence and Retention Analyses ..................................................................... 29 
10.4.6  
Baseline Descriptive Statistics.............................................................................. 29 
10.4.7 
Planned Interim Analyses .................................................................................... 30 
10.5 
Sample Size ............................................................................................................................ 30 
10.6 
Measures to Minimize Bias .................................................................................................... 30 
10.6.1 
Enrollment/ Randomization/ Masking Procedures ............................................. 30 
11 
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS............................................ 30 
12 
QUALITY ASSURANCE AND QUALITY CONTROL .............................................................................. 31 
13 
ETHICS/PROTECTION OF HUMAN SUBJECTS ................................................................................... 32 
13.1 
Ethical Standard ..................................................................................................................... 32 
13.2 
Institutional Review Board .................................................................................................... 32 
13.3 
Informed Consent Process ..................................................................................................... 32 
13.3.1 
Consent/assent and Other Informational Documents Provided to Participants 32 
13.3.2 
Consent Procedures and Documentation ............................................................ 32 
13.4 
Participant and data Confidentiality ...................................................................................... 32 
14 
DATA HANDLING AND RECORD KEEPING ........................................................................................ 32 

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SSU Protocol V6.0 9.20.2019 
14.1 
Data Collection and Management Responsibilities ............................................................... 33 
14.2 
Study Records Retention ....................................................................................................... 33 
14.3 
Protocol Deviations ................................................................................................................ 33 
14.4 
Publication and Data Sharing Policy ...................................................................................... 33 
15 
STUDY ADMINISTRATION ................................................................................................................ 36 
15.1 
Study Leadership.................................................................................................................... 36 
16 
CONFLICT OF INTEREST POLICY ....................................................................................................... 37 
17  
LITERATURE REFERENCES ................................................................................................................ 37 
 
 
 
 
 
 
 
 
 
 

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SSU Protocol V6.0 9.20.2019 
LIST OF ABBREVIATIONS 
 
AHF 
Acute Heart Failure 
US 
United States 
HF 
Heart Failure 
ED 
Emergency department 
EP 
Emergency Physician 
DAOOH 
Days alive and out of hospital 
NIV 
Non-invasive ventilation (positive pressure ventilation) 
NTG 
Nitroglycerin 
IV 
Intravenous 
SL 
Sub-lingual 
AKI 
Acute Kidney Injury 
WRF 
Worsening renal function 
WHF 
Worsening heart failure 
AE 
Adverse event 
SAE 
Serious Adverse Event 
SBP 
Systolic Blood Pressure 
Hgb 
Hemoglobin 
Hct 
Hematocrit 
IEC 
Institutional Ethics Committee 
IRB 
Institutional Review Board 
GCP 
Good clinical practice 
SSU 
Short Stay Unit 
OU 
Observation Unit 
QoL 
Quality of Life 
 
STATEMENT OF COMPLIANCE 
This study will be conducted in full accordance with the Good Clinical Practice: Consolidated Guideline approved by the 
International Conference on Harmonization (ICH) and any applicable national and local laws and regulations (e.g., 
Title 21 Code of Federal Regulations [21CFR] Parts 50, 54, 56, 312, and 314).  Any episode of noncompliance will be 
documented. 
The Investigators are responsible for performing the study in accordance with this protocol and the ICH and Good 
Clinical Practice (GCP) guidelines and for collecting, recording, and reporting the data accurately and properly.  
Agreement of each Investigator to conduct and administer this study in accordance with the protocol will be 
documented in separate study agreements with the sponsor and other forms as required by national authorities. 
Each Investigator is responsible for ensuring the privacy, health, and welfare of the patients during and after the study 
and must ensure that trained personnel are immediately available in case of a medical emergency.  
The Principal Investigator at each center has the overall responsibility for the conduct and administration of the study at 
that center and for contacts with study management, with the Independent Ethics Committee/Institutional Review 
Board (IEC/IRB), and with local authorities. 
 
 
 

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SSU Protocol V6.0 9.20.2019 
INVESTIGATOR AGREEMENT 
 
I have read this protocol and agree: 
• 
To conduct the study as outlined herein, in accordance with current Good Clinical Practices (GCPs), the guiding 
principles of the Declaration of Helsinki and complying with the obligations and requirements of Clinical 
Investigators and all other requirements listed in 21 CFR Part 312, local regulations, and according to the study 
procedures provided by Indiana University 
• 
Not to implement any changes to the protocol without prior agreement from Indiana University and prior 
review and written approval from the IRB/EC, except as would be necessary to eliminate an immediate hazard 
to study patient(s), or for administrative aspects of the study. 
• 
To ensure that all persons assisting me with the study are adequately informed about their study-related duties 
as described in the protocol. 
• 
To completely inform all patients in this study concerning the pertinent details and purpose of the study prior to 
their agreement to participate in the study in accordance with GCP and regulatory authority requirements. 
• 
That I will be responsible for maintaining each patient’s consent form in the study file and provide each patient 
with a signed copy of the consent form. 
 
Investigator Name and Title: 
 
 
 
Institution Address: 
 
 
 
 
 
 
 
Signature: _____________________________________________  
Date: ____________ 
 
PROTOCOL SUMMARY 
Title: 
Using Short Stay Units Instead of Routine Admission to Improve Patient Centered Health 
Outcomes for AHF Patients  
 
Précis: 
Of the over one million annual AHF hospitalizations, approximately 80% are initially 
treated in the emergency department (ED).1,2 AHF is the most common and costliest 
reason why patients over the age of 65 are hospitalized.3 While some clearly require 
admission, others do not.4,5 There is a spectrum of risk for ED patients with AHF.  Previous 
reports suggest 50% of patients could be discharged from the ED or observed for less than 
24 hours.4 Yet admission rates from the ED for AHF remain around 80%.6  From a patient 
perspective, we know patients and caregivers would prefer to spend as little time as safely 
possible in the hospital 
 
Using a multi-center, randomized controlled design, this clinical effectiveness trial will test 
whether Short Stay Unit AHF management for < 24 hours increases DAOOH and QoL 
compared to usual care, defined as in-hospital management.    
 

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SSU Protocol V6.0 9.20.2019 
Objectives: 
 
Aim 1: To demonstrate the effectiveness of a SSU AHF management strategy vs. usual AHF 
care (i.e. inpatient admission), using a randomized, controlled, simple, trial design.   
Aim 2: To demonstrate that a SSU AHF strategy of care leads to equivalent or improved 
adherence to HF guidelines at time of discharge vs. usual care (i.e. hospitalization). 
Endpoints 
Primary Endpoint: Days alive and out of hospital at 30 days post-discharge.   
Secondary Endpoints: 1) Quality of life as measured by Kansas City Cardiomyopathy 
Questionnaire 2) Cost-effectiveness analysis between the two arms at 30 days 
Exploratory Endpoints:  
1) Caregiver burden as measured by two Caregiver 
Burden Scales at 30 days; 2) Cost-Effectiveness of the SSU 
AHF strategy of care at 90 days; 3) Resource utilization 
measured by the Modified Resource Utilization 
Questionnaire for Heart Failure (mRUQ-HF) at 90 days 4) 
All cause mortality and re-hospitalization at 30 and 90 
days 5) Days alive and out of hospital at 90 days 6) HF 
Guideline adherence at time of discharge 
 
Population: 
ED patients with AHF who meet inclusion and no exclusion criteria will be enrolled once 
written informed consent is obtained. 
Phase: 
NA 
Number of Sites 
enrolling participants: 
Four.  Projected sample size, n=534. 
Description of Study 
Agent:  
SSU AHF care for < 24 hours vs. usual care (inpatient admission) in ED patients with AHF 
who lack baseline high-risk features. 
Study Duration: 
4.5 years.  There will be three months of start up, and three months of study conclusion 
work.  Enrollment will occur over 48 months. 
Participant Duration: 
90 days post discharge 
 

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SSU Protocol V6.0 9.20.2019 
SCHEMATIC OF STUDY DESIGN 
 
1 
KEY ROLES 
Our team of investigators is uniquely qualified to successfully complete this study. We leverage complementary 
experience and expertise, in particular, early (ED) enrollment, short stay unit (SSU) management, and clinical trials.  
Most importantly, we have worked close together for nearly 10 years.5,7-29 
Peter S. Pang MD (PI) is an Associate Professor in Emergency Medicine at the Indiana University School of Medicine (IU 
SOM).  
Xiaochun Li PhD, from the Department of Biostatistics at Indiana University School of Medicine will lead the Data Core 
at IU.  
Sean Collins MD (Vanderbilt University), Professor and Vice-Chair of Research, will the site PI at Vanderbilt.  
Susan Pressler PhD is a Professor of Nursing at the Indiana University School of Nursing. She helped develop the 
modified Resource Utilization Questionairre in Heart Failure and is an expert in quality of life assessments.  
2  
INTRODUCTION: BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE  
 
2.1 
BACKGROUND INFORMATION  

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SSU Protocol V6.0 9.20.2019 
Heart failure is a major public health burden.  Over 5.5 million Americans have heart failure (HF), with 870,000 new 
diagnoses each year.30 Within 5 years, half of these patients will be dead.30 By 2030, the prevalence of HF will increase 
46% and HF costs will increase, from $31 billion to $70 billion.31  Hospitalization for AHF consumes the majority of these 
dollars.32,33 HF is the most common reason why patients over the age of 65 are hospitalized.3 Hospitalization is not 
benign, marking patients at greatest risk for adverse outcomes.33,34 Re-hospitalized patients are at even greater risk.34 
After hospitalization, patients enter a vulnerable phase.35-38 During this vulnerable phase, approximately 20% of 
hospitalized patients experience another medical adverse event.35 Not only patients are affected; 
hospitalization/rehospitalization takes a toll upon families and caregivers.35 
The emergency department (ED) accounts for the majority of the one million hospitalizations for AHF annually. 
Approximately 80% of AHF admissions are initially treated in the ED.1,2 Unlike chronic HF, no AHF treatment definitively 
prolongs life or reduces the risk for re-hospitalization.39 Clearly some patients require admission, however a large 
proportion do not require prolonged hospitalization.4,5 Many AHF patients have congestion secondary to worsening 
chronic HF. These patients receive IV diuretic therapy and little additional pharmacologic management, despite a 
median length of stay of 4.3 days.1,22,25,40-42 This is one reason institutions advocate for outpatient ‘infusion centers’ or 
‘diuretic clinics.’43  Admitting and re-admitting lower risk AHF patients who don’t need it may increase their risk for poor 
outcomes and decrease their quality of life.  Safe alternatives to hospitalization from the ED are needed. A recent 
NHLBI working group identified alternatives to hospitalization from the ED as a high priority.15 The Institute of Medicine 
identified observation units as an opportunity to improve patient flow resource utilization.44 
2.2 
RATIONALE  
Small studies, retrospective analyses, and the Society for Cardiovascular Patient Care (SCPC; now American College of 
Cardiology [ACC] Accreditaiton Services) guidelines support brief observation (< 24 hours) or short stay unit (SSU) 
management of AHF to be effective for lower risk AHF patients. Our group’s early work demonstrated lower overall 
median length-of-stay compared to a risk-matched inpatient only group (25.7 vs 58.5 hours).45 Importantly, total 
charges were approximately $3600 less for the SSU compared with those admitted from the ED.  In a retrospective 
study of 358 patients using SCPC guidelines, the authors observed less hospital bed day utilization and similar 30-day 
readmission rates (12.5% vs 10.0%), respectively after adjustment for age, race, sex, BNP, renal function and ejection 
fraction.46 SSU discharges spent 2.4 days and 2.5 days within 30 and 90 days of follow-up, respectively, compared with 
4.4 and 5.0 days among patients admitted to the hospital after SSU management (p<0.0001).46 Those patients who 
weren’t ready for discharge after SSU management were admitted to the hospital for further treatment. However, 
several knowledge gaps hinder broad uptake of SSU management.  First, an adequately powered, randomized 
controlled trial of SSU AHF care has not yet been conducted. Second, the impact of a SSU AHF strategy on quality of life 
and caregiver burden is unknown. Third, due to reimbursement differences, patients may face increased out-of-pocket 
costs.  Finally, clinicians and caregivers may think SSU is just ‘gaming the system’ to avoid readmission penalties.  We 
address each of these gaps in our proposal. 
2.3 
POTENTIAL RISKS AND BENEFITS  
 
2.3.1 KNOWN POTENTIAL RISKS  
Patients will only receive current usual care for acute heart failure.  There will be no experimental drugs or therapies.  
However, the SSU are will receive protocolized care while the usual care arm will receive the non-protocolized AHF care 
per routine.  Past small studies and retrospective analyses demonstrate the safety and efficacy of SSU management. 
Furthermore, if SSU treated patients are not ready for discharge, they will be admitted. Thus, there is a built in ‘safety-
net.’ However, the SSU strategy has not been tested in a randomized, controlled, clinical trial. Nevertheless, there is a 
risk that patients will be discharged prematurely from either setting.  
2.3.2 KNOWN POTENTIAL BENEFITS  

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SSU Protocol V6.0 9.20.2019 
Patients enrolled in this study who are receiving the strategy-of-care or usual care may receive a benefit such as 
decreased mortality, or less frequent hospitalizations related to HF, or leave the hospital sooner, or improved quality of 
life.  If this study is positive, future patients may benefit from avoiding unnecessary time in the hospital, but equal or 
better outcomes.  
3 
OBJECTIVES AND PURPOSE 
Objectives: 
1: To demonstrate the effectiveness of a SSU AHF management strategy vs. usual AHF care (i.e. inpatient admission), 
using a randomized, controlled, simple, trial design.   
2. To demonstrate that a SSU AHF strategy of care leads to equivalent or improved adherence to HF guidelines at time 
of discharge vs. usual care (i.e. hospitalization). 
Purpose: 
The overarching goal of this comparative effectiveness study is to increase days-alive-and-out-of-the-hospital (DAOOH) 
and improve quality of life (QoL) for lower risk AHF patients who present to the emergency department (ED). We 
hypothesize an alternative to hospitalization, SSU AHF management of less than 24 hours, will achieve our goal.  
4 
STUDY DESIGN AND ENDPOINTS 
 
4.1 
DESCRIPTION OF THE STUDY DESIGN 
A prospective, randomized, controlled, simple, comparative effectiveness study of a strategy of care (SSU care) vs. usual 
care (inpatient admission) in ED patients with AHF who lack baseline high-risk features and ineligible for ED discharge.  
4.2.1 PRIMARY ENDPOINT 
Days alive and out of hospital at 30 days post-discharge.  
4.2.2 SECONDARY ENDPOINTS 
1) Quality of life as measured by Kansas City Cardiomyopathy Questionnaire 2) Cost effectiveness analysis between the 
two arms at 30 days. 
 
4.2.3 EXPLORATORY ENDPOINTS 
1) Caregiver burden as measured by Oberst Caregiving Burden Scale and Bakas Caregiving Outcomes Scale ; 2) Cost-
Effectiveness of the SSU AHF strategy of care at 90 days; 3) Resource utilization measured by the Modified Resource 
Utilization Questionnaire for Heart Failure (mRUQ-HF) 4) All cause mortality at 30 and 90 days 5) All cause re-
hospitalization at 30 and 90 days; 6) Days alive and out of hospital at 90 days 7) HF Guideline adherence at 30 days 
5 
STUDY ENROLLMENT AND WITHDRAWAL 
 
5.1 
PARTICIPANT INCLUSION CRITERIA 
1) ED physician clinical diagnosis of AHF;  
2) Planned admission for AHF 
3) Systolic blood pressure > 100mmHg*, heart rate < 115bpm. The last HR and SBP should be within 1 hour of 
randomization.  
4) Previous history of HF 
 

13 
SSU Protocol V6.0 9.20.2019 
*Patients with atrial fibrillation but controlled HR are eligible 
 
For Caregiver Burden assessments.  The eligibility criteria for a caregiver: 1) person either self-identifies, or when asked 
identifies themselves, as the primary caregiver for the patient.  If there are multiple caregivers, the person who self-
identifies as providing the most care will be asked to provide verbal  informed consent. This part of the investigation 
pses no more than minimal risk to the subject and caregivers will be provided with information about the study and the 
processes for the initial and 30 day follow up questionnaires. For patients with no caregiveridentified, no caregiver 
assessment will be performed.  
5.2 
PARTICIPANT EXCLUSION CRITERIA 
 
5.3 
STRATEGIES FOR RECRUITMENT AND RETENTION 
Sites will be initiated only after IRB approval and site training. Each site has well-established procedures for identifying 
potential subjects for AHF clinical trials.  Broadly, these are based on electronic screening of ‘tracking boards’ in the ED, 
alert systems generated by the electronic health record, and direct interaction with ED caregivers. Each site will also be 
required to utilize a ‘boots-on-the-ground’ approach.  While electronic aids may be used, each site must have research 
staff physically walk through the ED frequently throughout the day or stationed in the ED.  Patients with AHF will be pre-
screened by dedicated, trained, experienced research personnel to determine if eligibility criteria are met. Patients will 
then be approached to ascertain their willingness to participate after discussion with the patient’s primary caregiving 
team. Only after written informed consent will randomization occur. 
As a comparative effectiveness trial, the inclusion/exclusion criteria are relatively broad compared to other therapeutic 
clinical trials.   
Screen Failures: 
Patients who sign an informed consent but who are not randomized, or after randomization have a change in clinical 
status making them ineligible, will be considered Screen Failures. Only data for randomized patients will be entered into 
the CRF.  Serious adverse events should be reported for these patients from the time the ICF is signed through the time 
1) Patients hospitalized within the last 30 days ONLY if the institution mandates these patients are observed. 
Otherwise, these patients remain eligible. 
2) Transplanted organ of any kind or ventricular assist device patient;  
3) End stage renal disease, on dialysis, or eGFR < 20 mL/min;  
4) Acute coronary syndrome (e.g. EKG changes consistent with ischemia or troponin elevation secondary to 
ACS as per the treating ED clinician);  
5) Other acute co-morbid conditions (e.g. sepsis, altered mental status); 
6)Patients who require ventilatory support of any kind or intravenous vasodilators/vasopressor/inotropic support at the 
time of ED disposition 
7) Pregnant patients or any patient who has been pregnant in the last 3 months 
8)≤ 18 years of age 
9)Any patient who in the opinion of the clinician or investigator should not be in an obs unit or requires ICU level care or 
will require inpatient rehabilitation or skilled nursing facility after discharge from the ED or hospital 
10) Planned discharge from the emergency department  
11) De novo (new onset) AHF 

14 
SSU Protocol V6.0 9.20.2019 
that the patient is declared a screen failure.  One expected reason for screen failure will be a change in plan to 
discharge the patient from the ED. 
Minimizing loss to follow-up (LTFU), as well as completion of 30-day and 90-day vital status assessments and 
QoL/Caregiver Burden questionnaires, are critical to study success.  Every effort will be made to ensure follow-up with 
patients and caregivers at 30 and 90 days, including phone call, text messaging, email, regular mail, and electronic 
health record review.  Based on the extensive experience at each site, we do not anticipate a large LTFU rate.  However, 
our sample size calculations account for attrition (see below). 
5.4 
PARTICIPANT WITHDRAWAL OR TERMINATION 
 
5.4.1 REASONS FOR WITHDRAWAL OR TERMINATION 
In accordance with the guiding principles of the Declaration of Helsinki, any patient is free to withdraw from 
participating in this study at any time and for whatever reason, specified or unspecified, and without prejudice. 
Investigators should attempt to determine the cause of withdrawal and, if desired by the patient, to make it possible for 
the patient to continue to participate in the study.  The extent of a patient's withdrawal from the study (i.e. withdrawal 
from further study treatment, withdrawal from any further contact, etc.) should be documented.  Every effort should be 
taken to follow all randomized patients, to the extent that the patient will allow, for the full follow-up period. 
Investigators may discontinue study treatment for any other reasons concerning the health or well-being of the patient. 
The reason for and date of study discontinuation and the reason for and date of withdrawal from the study must be 
recorded on the CRF.  If study is discontinued because of an adverse event or a clinically significant abnormal laboratory 
test result, evaluations will continue until the event has resolved or stabilized or until a determination of a cause 
unrelated to the study procedure is made.  The specific event or laboratory finding(s) must be documented.  All 
evaluations should be performed, according to the protocol.   
5.4.2 HANDLING OF PARTICIPANT WITHDRAWALS OR TERMINATION 
The Full Analysis Set (FAS) will include all randomized patients. In accordance with the intent-to-treat principle, patients 
will be analyzed by the group to which they were randomized. Misrandomized patients (patients randomized in error 
who did not receive any study intervention) will be excluded. Analyses in the FAS will constitute the main efficacy 
results for the primary and secondary study efficacy endpoints. 
The Per Protocol Set (PPS) will be a subset of the FAS and will exclude patients with major protocol violations.   The 
major protocol violations that will result in exclusion from the PPS will be identified. Patients will be analyzed in the 
treatment group to which they were randomized. Results of analyses in this analysis population will support the primary 
efficacy analyses in the FAS. 
5.5 
PREMATURE TERMINATION OR SUSPENSION OF STUDY 
The study is overseen by a DSMB.  They may terminate the study at any time if the safety of patients is at jeopardy. 
6 
STUDY AGENT 
 
6.1 
STUDY AGENT(S) AND CONTROL DESCRIPTION 
This study will test a strategy-of-care, SSU AHF management for less than 24 hours vs. usual care (hospitalization) for 
lower risk AHF patients who are planned to be admitted.  Only therapies commonly utilized during usual AHF care will 
be applied.  For example, , IV loop diuretics, and topical and oral vasodilators.  Usual care will be at the discretion of the 
clinical care team.  No drugs or therapies that are not approved by the FDA will be allowed. 
6.1.1 TREATMENT PROTOCOL 
The algorithm below outlines the SSU AHF protocol. 

15 
SSU Protocol V6.0 9.20.2019 
 
Arm 1. SSU AHF Strategy: ‘Short stay’ is defined as < 24 hours. All SSU are monitored beds. Nursing ratios are similar to 
telemetry wards. Four principles of SSU AHF management are outlined: 1) relief of HF symptoms and signs; 2) 
decongestion while observing and correcting any electrolyte imbalances; 3) hemodynamic improvement; and 4) robust 
care transitions with an emphasis on guideline directed medication reconciliation and guideline recommended therapy 
at discharge.16,46 One potential advantage of the SSU AHF strategy is protocol driven care.  (See Figure 3, next page) This 
figure is adapted from the ESC and SCPC Guidelines, primarily adding greater detail regarding vasodilator and diuretic 
dosing.47  “Warm and wet” defines the HF phenotype from the Nohria et.al. classification: well perfused, volume 
overloaded.48 The discharge criteria are taken from the SCPC guidelines on observation unit care.16 
Arm 2. Usual care (defined by inpatient admission for AHF) was chosen as the comparator. In 2009, Dawson et.al. 
published the background framework for the 2005 NIH funded meeting on “Considering Usual Care in Clinical Trial 
Design: Scientific and Ethical Issues.”49 These principles informed our decision to use ‘usual care’ as the comparator. 

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SSU Protocol V6.0 9.20.2019 
One specific principle: consideration of ‘usual care’ when a comparator hypothesizes to be better than or equivalent to 
current clinical practice.49 Hospitalization is the dominant strategy of care for over 80% of patients who present to the 
ED with AHF; thus, it provides the best real-world comparison of AHF care.50 The median length of stay is 4.3 days.1  We 
expect nearly all usual care patients to be cared for on general wards or telemetry and not ICU level of care, given our 
lower risk eligibility criteria.  Guidelines are clear on suggested best practices for management.49  Admittedly, the 
evidence supporting these statements in AHF are not as robust as chronic HF. This is one reason usual care has 
frequently been used in AHF therapeutic clinical trials.51-53 Nevertheless, we will encourage guideline adherence in 
BOTH arms of the trial, both during hospitalization and pre-discharge. As hospitals are penalized on excessive 30-day 
readmissions, each participating hospital has a transitional care plan.  In keeping with the pragmatic study design, each 
study arm will utilize their existing transitional care programs.  
6.1.2 DURATION OF THERAPY 
Both arms will continue until patients are deemed ready for discharge, either from the SSU or the hospital. For patients 
deemed not ready for discharge after the SSU management phase, will be admitted. 
7 
STUDY PROCEDURES AND SCHEDULE 
 
7.1 
STUDY PROCEDURES/EVALUATIONS 
7.1.1 STUDY SPECIFIC PROCEDURES  
The table below in section 7.3.7 highlights study specific procedures.  Only patients who sign written informed consent 
will under study specific procedures. 
7.1.2 STANDARD OF CARE STUDY PROCEDURES  
There will be no other change to standard of care procedures for either treatment arm. Patient care and safety are 
paramount and trump all other considerations.   
7.2 
LABORATORY PROCEDURES/EVALUATIONS 
 
7.2.1 CLINICAL LABORATORY EVALUATIONS  
Lab testing will be based on standard practice and likely include analyzed by the clinical lab at each respective 
institution for baseline chemistry and hemoglobin/hematocrit values. This reflects our pragmatic approach. Only labs 
collected as part of usual or standard care will be collected. No lab testing will be done solely for research purposes.   
If drawn, all clinical laboratory test results outside of the reference range will be interpreted in the context of the 
patient underlying disease state by the Investigator using the following categories: 
• 
abnormal but not a clinically-significant worsening 
• 
abnormal and a clinically-significant worsening 
A local laboratory will be utilized to analyze screening entry criteria. Laboratory tests not specified in the protocol but 
required by the Investigator to assess patient care will be performed at the local laboratory in accordance with Standard 
of Care.   
 
7.3 
STUDY SCHEDULE 
7.3.1 SCREENING 
A signed and dated informed consent form will be obtained before any study-specific screening procedures are 
performed.  Results of evaluations obtained as part of routine medical care, which are performed prior to obtaining 

17 
SSU Protocol V6.0 9.20.2019 
informed consent, may be used in place of the protocol-specified evaluations.  Patients will acknowledge and agree to 
the use of this information for the study by giving informed consent.  
At the Baseline Visit, patients will be assigned by the IWRS a unique permanent identification number (referred to as 
the patient identification number) such that all randomized patients from each center are given consecutive 
identification numbers by the IWRS in successive order of inclusion.  We will utilize the REDCap randomization module. 
Prospective study patients will have presented to the hospital for urgent therapy for AHF.  Potential patients will be 
identified either en route to or upon arriving at the ED/hospital. Routine assessments associated with usual patient care 
may be used for the purposes of screening and may be completed in any order. Study specific procedures must be 
completed only after Informed Consent is obtained.  
Randomization will occur during the patients ED stay.  This may occur at any time during their ED stay. 
The following procedures will be performed prior to or during Screening: 
• 
Obtain written informed consent (must be performed as the first study-specific procedure) 
• 
Review and record medical history 
• 
Record prior and concomitant medications 
• 
Physical examination (including height and weight when reasonably possible) 
• 
Vital signs measurements (includes systolic and diastolic blood pressures, heart rate, body temperature, oxygen 
saturation reading and respiratory rate) 
• 
12-Lead Electrocardiogram per standard practice 
• 
Blood collection for local laboratory tests, including BNP or NT-proBNP, and pregnancy test if applicable per 
local standard practice. 
• 
Inquiry about Adverse events 
7.3.2 ENROLLMENT/BASELINE 
Patients who continue to fulfill all of the inclusion/exclusion criteria will be randomized. Randomization will occur via 
central IWRS system.  
7.3.3 FOLLOW-UP & FINAL STUDY VISIT 
Patients will have follow up at 30 (+/- 7 days) days and 90 (+/- 30) days post-discharge (up to 120 total days after 
randomization is allowed if difficult to get a hold of a patient or more time is required to complete forms).  There will be 
NO further in-person visits once discharged.  However, treatment during hospitalization will be recorded. Patients will 
be called 30 days post-discharge ((+) 7 business days) and 90 days post-discharge (+/- 30 days) to assess vital status, re-
hospitalizations or ED visits, as well as quality of life, caregiver burden, and resource utilization. 
 
 

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7.3.7 SCHEDULE OF EVENTS TABLE 
Schedule of Events 
Timepoint/Visit 
Screen 
Baseline 
ARM 1 - 
PreDischarge from 
SSU 
ARM 2 - 
PreDischarge from 
Hospital Floor 
30-Day & 
90 Day 
Follow up 
Informed Consent 
X 
  
  
  
  
Medical History 
  
X 
  
  
  
Physical Exam 
  
X 
X 
X 
  
Clinical lab tests* 
  
X 
X~ 
X~ 
  
ECG* 
  
X 
  
  
  
CXR* 
  
X  
  
  
  
KCCQ (QoL) & SF-12 
  
  
X 
X 
X 
Oberst Caregiving Burden Scale 
and Bakas Caregiving 
Outcomes Scale 
  
  
X 
X 
X1 
HF Guideline Assessment 
  
  
X 
X 
  
Collect concomitant meds 
  
X 
X 
X 
 
mRUQ-HF (resource utilization) 
 
 
 
 
X^ 
 
  
  
  
  
 
Cost Effectiveness Measures 
(i.e. DRG) 
  
  
  
  
X 
Guideline adherence 
assessment 
 
X 
X 
X 
X1 
SCPC Discharge Criteria 
Adherence 
 
 
X 
X 
 
Assessment of AE/SAE's 
through 5 days 
  
  
X 
X 
 
Vital Status, ED visits, Hospital 
days, Re-admission status 
  
  
X 
X 
X 
Subject Payment 
  
  
X 
X 
X2 
*per standard of care. Typical labs include: Na, K, renal function, HgB, troponin, Natriuretic Peptide levels. ~only if 
performed per usual care 
SOC = standard of care, ED = Emergency Department,  QoL = quality of life, HF = heart failure, mRUQ = modified 
resource utilization questionnaire, EMR = electronic medical record, DRG = diagnosis related group 
1Only through 30 days 
2Sites may choose to make a single payment or to divide into 2 payments.   
^only at 90 days 
NOTE: If patients are hospitalized from the SSU, ONLY the following assessments should be collected.  Otherwise, the 
pre-discharge assessments will apply. 
- 
Physical exam 
- 
Clinical lab tests 
- 
Con meds 
- 
SCPC discharge criteria. This would  be  conducted twice. Once in SCPS prior to hospitalization and again at 
discharge. 
 
7.5 
CONCOMITANT MEDICATIONS 

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All medications administered within 14 days prior to and during screening will be recorded in the case report form.   
Medications that are not specifically prohibited are permitted at the Investigator’s discretion. 
7.6 
PROHIBITED MEDICATIONS, TREATMENTS, AND PROCEDURES  
No medications, treatments, or procedures are prohibited unless specifically mentioned in the eligibility criteria.  
Patient safety and well-being are paramount: Any treatment deemed necessary may be utilized at the investigators 
discretion should there be any concern for the patients health. 
8 
ASSESSMENT OF SAFETY 
In addition to standard safety monitoring by the sponsor, an independent DSMB will oversee patient safety in the 
trial.  The DSMB will meet as specified in its charter. 
8.1 
SPECIFICATION OF SAFETY PARAMETERS 
Mortality, re-hospitalization, and ED visits through 30 and 90 days will be assessed for safety as well as efficacy 
8.1.1 DEFINITION OF ADVERSE EVENTS (AE) 
The Investigator and study staff are responsible for detecting and recording AEs and SAEs during scheduled safety 
evaluations and whenever such information is brought to their attention. This section of the protocol provides 
definitions and detailed procedures to be followed. During each visit, the Investigator will question the patient about 
adverse events using an open question, taking care not to influence the patient’s answers, e.g. “Have you had any 
unusual symptoms or medical problems since the last visit?  If yes, please describe.” 
An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an 
investigational (medicinal) product or other protocol-imposed intervention, regardless of attribution. It is expected that 
many HF patients will have events that are commonplace due to their HF and associated comorbidities. Our study plans 
to focus on AE that are outside of what is typically encountered during an AHF event and the subsequent 90 days.  
This includes the following:  
• AEs not previously observed in the subject that emerge during the protocol-specified AE reporting period (5 days for 
anything other than mortality, re-hospitalization, and ED visits)  
• Complications that occur as a result of protocol-mandated interventions such as a medication adjustment  
• Preexisting medical conditions (other than the condition being studied) judged by the investigator to have worsened 
in severity or frequency or changed in character during the protocol-specified AE reporting period that are outside of 
what would be expected for a patient with AHF or HF in the outpatient setting.  
 
For example, a patient upgraded to ICU status from the observation or SSU.  Hospitalization, by itself, does NOT 
count as it is expected to occur for a proportion of SSU patients. 
• Abnormal laboratory values that fall into an abnormal range based upon the hospital’s laboratory standards, the 
abnormality was not preexisting prior to enrollment, and the abnormality leads to a new treatment within the AE time 
frame, with the exception of repleting potassium. 
8.1.2 DEFINITION OF SERIOUS ADVERSE EVENTS (SAE) 
An AE will be classified as an SAE if:  
• It results in death (i.e., the AE actually causes or leads to death).  
• It is life threatening (i.e., the AE, in the view of the investigator, places the subject at immediate risk of death. It does 
not include an AE that, had it occurred in a more severe form, might have caused death).  
• It requires or prolongs inpatient hospitalization. Admission from the SSU itself does not count as an SAE, but an 
expected outcome. However, if in the investigators judgment, admission from the SSU was due to some other 
complication of the study protocol, rather than an expected outcome, it should be reported as an SAE 
 
SPECIFIC REPORTABLE SAE for SSU/OU arm patients: 
- 
Cardiac arrest 

20 
SSU Protocol V6.0 9.20.2019 
- 
Need for intubation or positive pressure ventilation 
• It results in persistent or significant disability/incapacity (i.e., the AE results in substantial disruption of the subject’s 
ability to conduct normal life functions).  
• It is considered a significant medical event by the investigator based on medical judgment (e.g., may jeopardize the 
subject or may require medical/surgical intervention to prevent one of the outcomes listed above).  
 
8.2 
CLASSIFICATION OF AN ADVERSE EVENT 
 
8.2.1 SEVERITY OF EVENT 
The severity of each adverse event must be recorded as 1 of the choices on the following scale: 
Mild 
 
No limitation of usual activities 
Moderate 
Some limitation of usual activities 
Severe  
Inability to carry out usual activities 
An AE that is assessed as severe should not be confused with a SAE. 
8.2.2 RELATIONSHIP TO STUDY PROTOCOL 
Each reported AE will be described by its duration (i.e., start and end dates), regulatory seriousness criteria if applicable, 
and suspected relationship to study protocol in accordance with definitions set forth at each IRB. In general, these 
relationships are categorized as likely, possible, unlikely and not related. Experience teaches that gray zone instances 
will arise, and the site coordinators and PIs will be trained to adjudicate possible SAEs in a systematic fashion. To ensure 
consistency of SAE causality assessments, investigators will apply the following general guideline:  
Yes - There is a plausible temporal relationship between the onset of the AE and administration of the study protocol 
and the AE cannot be readily explained by the subject’s clinical state, inter-current illness, or concomitant therapies; 
and/or the AE follows a known pattern of response to study drug or the AE abates or resolves upon discontinuation of 
study drug;  
No - Evidence exists that the AE has an etiology other than the study protocol (e.g., preexisting medical condition, 
underlying disease, inter-current illness, or concomitant medication); and/or the AE has no plausible temporal 
relationship to the study drug.  
Adjudication of each AE will proceed as follows: First, the coordinator will consult the site PI to review the chart. Next, 
the PI will contact members of the clinical care team to clarify uncertainty related to inadequate documentation. Third, 
if the PI is unable to decide for certain if an AE or SAE occurred, he or she will have the option of sending a personal 
health identifier-stripped, written narrative of the event to the other site PIs who will vote up or down as to whether 
the event constituted an AE or SAE.  
8.2.3 EXPECTEDNESS  
The following signs, symptoms, observations and events are frequently observed in association with acute heart failure 
and its treatments are exempted from regulatory reporting (including, but not limited to local IRB) unless known to be 
caused by, or plausibly caused by spironolactone: dyspnea, orthopnea, paroxysmal nocturnal dyspnea, chest pain, fever, 
hypoxemia, rapid pulse, rapid respiratory rate, dizziness, syncope, altered mental status, confusion, anxiety, generalized 
weakness, anorexia, nausea, abdominal pain, back pain, early satiety, vomiting, pneumonia, acute renal failure, 
repleting potassium, skin infection, cancer, surgery not related to treatment of pulmonary embolism, 
electrocardiography abnormalities (atrial arrhythmias, ventricular dysrhythmias, right bundle branch block, and ST and 
T wave changes), elevated troponin level, elevated BNP or NT ProBNP level, high white blood cell count,  pulmonary 
infiltrate, pleural effusion, cardiomegaly, electrolyte imbalances, need for oxygen therapy, need for vasopressor 
support, need for blood product transfusion, need for mechanical ventilation (invasive or non-invasive), need for 
physical or occupational therapy, need for analgesia, need for skilled nursing facility upon discharge, need for early 
follow up with physician, escalation of heart failure therapy, need for cardiac catheterization or PA line placement, need 
for sleep study.  

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8.3 
TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP 
All AEs and SAEs will be followed through resolution, stabilization, or until the subject is lost-to-follow-up.  
The onset and end dates, duration, action taken regarding study drug, treatment administered, and outcome for each 
adverse event must be recorded on the CRF for randomized patients.  The relationship of each adverse event to study 
procedures, and the severity and seriousness of each adverse event, as judged by the Investigator, must be recorded as 
described below. 
8.4 
REPORTING PROCEDURES 
8.4.1 ADVERSE EVENT REPORTING  
The study period during which AEs must be reported begins after informed consent is obtained and initiation of study 
treatment and for 5 days after randomization. Patients will be followed out to 90 days for death, ED utilization, and re-
hospitlization as part fo the study outcomes, which will also count as safety measures. Subject’s hospital discharge 
summaries will be examined at hospital discharge and all non-exempt AEs will be investigated by examining necessary 
medical records.  
8.4.2 SERIOUS ADVERSE EVENT REPORTING  
All SAE’s will be reviewed within 48 hours and all AE’s within 7 days of discovery. SAE’s will be followed through the 
entire follow up period (i.e. through day 30). Any SAE discovery will be reported to the DCC who will then report to the 
DSMB. If placebo treated patient, standard reporting to the IRB will occur.  If active treated patient, and deemed to be 
related to drug, the SAE will be reported to the DSMB chair within 7 business days by email, fax, or phone of any fatal or 
life-threatening adverse event that is unexpected.  
15 Calendar Day Written Report  
The Investigator will also be required to notify the IRBs and all participating investigators, in a written Safety Report, of 
any serious, unexpected AE that is considered reasonably or possibly related to the strategy-of-care arm  
72 hour reporting 
For the discovery of an unexpected serious adverse event thought to be related to study procedures the Investigator(s) 
will notify the Chair of the DSMB by email within 72 hours. 
 
8.5 
STUDY HALTING RULES  
Please see separate DSMB Charter 
8.6 
SAFETY OVERSIGHT 
Please see separate DSMB Charter 
9 
CLINICAL MONITORING 
Sites will be remotely monitored.  Should the need arise for further investigation, an independent monitor will be 
appointed to visit sites.  Each site has extensive clinical trial experience and the expectation for this need is low.  
Nevertheless, the PI will visit each site at least once per year for meeting with study staff and random surveillance. 
10 
STATISTICAL CONSIDERATIONS  
10.1 
STATISTICAL AND ANALYTICAL PLANS 
Data Coordinating Center (DCC): The DCC will be housed at the Indiana University School of Medicine in the 
Department of Biostatistics, led by Xiaochun Li PhD.  She will oversee data management and analysis related activities. 
The DCC will perform the following activities and functions: 
• Overall responsibility for the biostatistics related to the trial.  In this function, guidance and leadership will be 
provided regarding clinical trial methodology as well. 

22 
SSU Protocol V6.0 9.20.2019 
• Facilitate good study communication will be facilitated regarding trial progress and enrollment. 
• Trial analysis and trial reports will be generated, including reports on the individual components of the study 
intervention – at both the site and overall study level – to ensure fidelity of each aspect of the study 
• Database reports to monitor accrual as well as data quality, with queries generated to sites as needed 
• Liaison with the DSMB and provide biostatistical support.   
• Facilitate dissemination of the trial results through analysis and participation in the writing of study reports as well 
as manuscripts and presentations. 
• Develop a Data Management Plan (DMP) in collaboration with participating sites of the study.  
• Creation and maintenance of the eCRF  
• Monitor patient enrollment and data collection by participating sites.  
• Establish database lock procedures and clear change-control procedures for unlocking the database 
• Produce protocol violation and deviation reports, missing data reports and data discrepancies reports will be 
generated. Automated edit checks both within and across CRFs and visit dates will be constructed by the DCC Data 
Manager.  Queries generated will be forwarded by the DCC Data Manager to all participating sites’ research 
coordinators for resolution.  
 
10.1.1 ENDPOINTS AND RATIONALE 
To ensure patient-centered endpoints, we twice met with patients and caregivers through two community engagement 
studios.54 Patients prefer to be healthy and have a good QoL. If a safe alternative is available,  patients prefer not to be 
hospitalized. 
The primary outcome is days alive and out of hospital (DAOOH) at 30 days post-randomization. Unlike time-to-event 
analyses that ignores repeat events and gives equal weight to components of a composite endpoint,55 DAOOH accounts 
for both frequency and duration of hospitalization and also weights mortality most heavily.55,56 This endpoint has also 
been suggested as a quality metric rather than re-hospitalization alone.57 
The two secondary outcomes are 1) QoL using the KCCQ. Patients desire not only to live longer, but to live better; or at 
minimum, not be worse after an acute health care related event.58 Patients with advanced HF would trade survival time 
(or days alive) for a better QoL.58 Our pilot work supports the feasibility of assessing QoL in the acute setting and 
suggests changes in scores are related to hospital re-visits.59 We hypothesize that fewer days in the hospital in our SSU 
arm will also lead to a greater QoL. Interviews of hospitalized AHF patients suggest they would prefer a shorter hospital 
stay or avoid an admission altogether, assuming safety and outcomes are similar or better than hospitalization. Thus, 
assessing QoL is a key aim. 
The KCCQ is a patient-reported, validated survey instrument designed to measure QoL in chronic HF patients.60  Lower 
scores equal lower patient-reported QoL. KCCQ scores predict adverse outcomes – namely hospitalization and 
mortality.  Importantly, the KCCQ demonstrates responsiveness to clinical change.60-62  
A change of five points has been previously shown to be clinically significant, and will be assessed prior to discharge and 
day 30 post-randomization.62  
2) Cost effectiveness analysis, described in detail below. 
NOTE: For patients randomized to SSU who worsen PRIOR to going to SSU, this will be counted the same as a 
hospitalization from the SSU. 
ADDITIONAL ENDPOINTS 
Adherence to guidelines saves lives and reduces hospitalizations and re-hospitalizations. We expect both the primary 
and secondary outcome will be affected by adherence to guidelines.  Advances in medical therapy for HF patients with 
reduced ejection fraction (EF) prolongs life and decreases hospitalization.39 Yet a substantial proportion of patients are 

23 
SSU Protocol V6.0 9.20.2019 
either not taking guideline-recommended medications or are on sub-optimal doses.63,64 We will emphasize and measure 
guideline adherence for eligible patients at the point of discharge from both study arms as well as during follow up. 
Guideline adherence: the following HF measures will be assessed in eligible patients:47,65-67 (1) assessment of left 
ventricular function within a 12 month period, (2) use of angiotensin-converting enzyme inhibitor or angiotensin 
receptor blocker or ARNI (angiotensin receptor blocker/neprilysin inhibitor) for left ventricular systolic dysfunction 
(defined as an ejection fraction < 40%), (3) Use of guideline recommended Beta-blocker for left ventricular systolic 
dysfunction, (4) use of mineralocorticoid receptor antagonists (5) use of ivabradine (6) use of hydralazine/isosorbide 
dinitrate (7) provision of discharge instructions, (8) counseling for smoking cessation, and (9) follow up appointment 
provided within 7 days of discharge. A composite heart failure measure will be created by averaging all quality 
measures available per patient. Specifically, the composite score is defined as the total number of interventions 
performed divided by the total number of interventions for which the patient was eligible.  In addition, we will assess 
for therapies prescribed inappropriately such as glitazones or ARNI prescribed simultaneously with an ARB. 
 Decreasing hospital stays may increase caregiver burden. Thus, we will also assess caregiver burden, using both the 
Oberst Caregiver Burden and Bakas Caregiver Outcome Scales, both validated instruments prior to discharge and again 
at 30 days.68 Other measures of caregiver burden in HFhave either not involved input from actual caregivers or missed 
important conceptual domains.68  Effective caregivers has been associated with improved quality of life, lower 
hospitalization rates, and reduced mortality.68,69 As our primary focus is on the patient, the eligibility criteria for the 
caregiver will be broad, essentially including any person who after separate written informed consent, acknowledges 
themselves as the primary caregiver for the patient.   
Out-of-pocket costs directly impact patients.  As such, we will assess healthcare utilization from a societal perspective 
using the Modified Resource Utilization Questionnaire for Heart Failure (mRUQ-HF).70 The mRUQ-HF is a14-item self-
report questionnaire of comprehensive lists of choice related to healthcare utilization. (See Appendix trial protocol)  
Exploratory analysis will occur in two steps: 1) Determination of resources consumed or related; 2) Assignment of 
‘value’ to the resources consumed.71  This two-step process allows for transparency of assigned costs.  Hospital costs 
will be assigned per individual hospital cost-accounting. Where monetary values are not directly self-reported, 
Medicare fee schedules will be used for uniformity. 
10.2 
STATISTICAL HYPOTHESES 
Aim 1: To demonstrate the effectiveness of a SSU AHF management strategy vs. usual AHF care (i.e. inpatient 
admission), using a randomized, controlled, simple trial design.   
• 
Hypothesis 1a: SSU treated patients will have one more DAOOH within 30 days post-randomization vs. usual 
care arm. Assuming a 10% attrition rate, we will randomize 534 patients 1:1, which will provide 80% power 
(alpha 0.05, two-sided) to demonstrate a one-day difference in the primary outcome at 30 days post-
randomization.  
• 
Hypothesis 1b: An AHF SSU strategy of care will lead to significant improvement in QoL scores at 30 days post-
discharge compared with usual care. QoL will be assessed with the KCCQ.59 
Aim 2: To demonstrate if a SSU AHF strategy of care leads to equivalent or improved adherence to HF guidelines at time 
of discharge compared to usual care. 
• 
Hypothesis 2: Adherence to HF guidelines at time of discharge in the SSU arm is equivalent or better than 
adherence in the usual care arm.  
10.3 
ANALYSIS DATASETS 
The Full Analysis Set (FAS) will include all randomized patients. In accordance with the intent-to-treat principle, patients 
will be analyzed by the group to which they were randomized. Misrandomized patients (patients randomized in error 

24 
SSU Protocol V6.0 9.20.2019 
who did not receive any study intervention) will be excluded. Analyses in the FAS will constitute the main efficacy 
results for the primary and secondary study efficacy endpoints. 
The Per Protocol Set (PPS) will be a subset of the FAS and will exclude patients with major protocol violations.   The 
major protocol violations that will result in exclusion from the PPS will be identified. Patients will be analyzed in the 
treatment group to which they were randomized. Results of analyses in this analysis population will support the primary 
efficacy analyses in the FAS. 
10.4 
DESCRIPTION OF STATISTICAL METHODS 
10.4.1 GENERAL APPROACH 
Unless stated otherwise, two-sided p values < 0.05 will be considered statistically significant, without regard to multiple 
comparisons. Statistical tables and listings and analyses will be produced using SAS release 9.1 or later (SAS Institute, 
Inc, Cary, NC, USA) or other validated statistical software. 
10.4.2 ANALYSIS OF THE PRIMARY EFFICACY ENDPOINT(S) 
Patient baseline characteristics will be tabulated for both SSU and usual care groups. Specifically, means (standard 
deviations) or medians (interquartile range) will be presented for continuous variables such as age and body mass 
index. For categorical variables, such as gender and race, frequency and percentages will be presented. Group 
comparisons of continuous variables will be based on either two-sample t-tests (under normality) or Wilcoxon’s Rank 
Sum test. Normality of distribution will be determined using the Kolmogorov-Smirnov goodness-of-fit test. Categorical 
data comparisons will be presented based on the Chi-square or Fisher’s exact test. Standardized difference is used to 
compare the mean of the SSU and usual care groups.72  
In-hospital and SSU measurements: Data points collected during hospitalization and the SSU (e.g. medications, therapy, 
changes in renal function, and discharge medications) will be compared between the SSU and usual care groups using 
the same methods as for baseline variables. A two-sided p-value less or equal to 0.05 is considered statistically 
significant (without multiplicity adjustment). 
Comparison on DAOOH (primary outcome): The DAOOH will be compared between the two arms using two-sample t-
test.  Statistical significance will be declared at 5% level (two-sided). We will also fit a linear regression model, which 
includes the intervention arm indicator and the site variable (e.g. a categorical variable with four levels) as the 
covariates. The regression model will account for variation among sites so that the power in detecting intervention 
effect can be improved. It will also allow us to assess potential heterogeneity in intervention effect among sites through 
testing the interaction between the two covariates. 
Capture of DAOOH Endpoint: Each study site uses an electronic health record with time stamps for ED arrival, time 
leaving the ED, time of arrival to SSU or inpatient admission, and time of discharge. Thus, exact times, rounded to the 
nearest hour, will be calculated to determine length of stay. Any time spent in the ED, SSU, or inpatient admission will 
count against their DAOOH.  Although the endpoint uses the term ”hospital,” for the purposes of this analysis and its 
patient-centered focus, any time in these three hospital settings (ED, SSU, inpatient admission) will be counted. If a 
patient returns to the hospital or to the ER, the time spent (in hours) will be added to their total length of stay.  This 
time does not need to be consecutive.  
10.4.3 ANALYSIS OF THE SECONDARY ENDPOINT(S) 
QoL: An AHF SSU strategy of care will lead to significant improvement in QoL scores at 30 days post-discharge compared 
with usual care. QoL will be assessed with the KCCQ.59 

25 
SSU Protocol V6.0 9.20.2019 
Sample Size Calculation:  The standard deviation of 1-week KCCQ change after acute heart failure is 20.8.73 Below are 
the numbers of subjects (both arms combined) required to detect various 
intervention effects with 80% power and type I error controlled at 0.05 
(two-sided) in the table. 
Similarly, the number of subjects (both arms combined) required to 
detect various effect size for caregiver burden (CB) with 80% power and 
type I error controlled at 0.05 (two-sided) is listed below. The effect size 
is defined as the difference in CB score divided by the standard deviation. 
It is a widely-used measure of treatment effect, which is used here 
because the standard deviation of CB in the target population if it has not 
been robustly studied.  Because we changed CB scales, we will use 
established MCID for each established scale. 
KCCQ QoL Analysis: The KCCQ will be compared between the two arms using the same method as in Aim 1. We will 
consider three ways of analysis with different outcomes based on KCCQ scores. First, we will exclude subjects who die 
without KCCQ in the analysis. Second, we will set KCCQ=0 for those who die without the 30-day KCCQ and include these 
people in the analysis. Third, we will create a composite binary endpoint of KCCQ<c or death, where c is a threshold. 
Chi-square test and logistic regression will be used to compare this outcome. We will select several relevant values for 
the threshold c and tabulate the results. The three analysis schemes allow us to understand how robust the comparison 
of KCCQ is with respect to different treatments of death.  
Cost-Effectiveness Analysis: 
To assess the effectiveness of short stay unit (SSU) management, we will analyze the patient outcomes as 
defined by cost, quality-of-life (QOL), medical utilization, and caregiver burden using regression analysis, and 
combine these results into a multifaceted incremental cost-effectiveness ratio (ICER).   
 
Here, ESSU and CSSU are the effectiveness and cost, respectively, of the SSU, while the EH and CH are the 
effectiveness and cost of the hospital admission.  The incremental cost effectiveness ratio allows us to 
estimate the additional cost associated with SSU treatment proportionate to the increased effectiveness of its 
patient outcome.  We expect SSU treatment to dominate hospital admission, resulting in greater effectiveness 
at a lower cost.1,2 Therefore, we expect ICER to be negative, reflecting the cost savings of implementing SSU 
treatment.   
Our goal is to evaluate the cost-effectiveness of the SSU strategy from a societal perspective, as we will 
account for the costs of care from both the hospital/insurer perspective and patient point-of-view.  As 
discussed in more detail below, our primary challenges lie in obtaining accurate and complete costs incurred 
by the patient outside of the hospital setting.  Given this potential limitation, at minimum, our CEA evaluation 
will be from the hospital/payer perspective.   
We will use an episodic approach to costing, which accounts for any cost shifting to a later point in time. This 
is the preferred approach for the Centers for Medicaid and Medicare services.  Specifically, we will examine 
the total cost of patient care from the index ED visit (study enrollment) for a period of 30 days.  In the context 
of the episode, we will analyze the incidence of readmission, total days of hospitalization, utilization of 
outpatient care, total cost, and caregiver burden. 
The outcome variables of interest are cost, effectiveness, and other characteristics of participant experience.  
Costs will be defined by total billable hospital costs (Table 1) and patient costs.  Hospital costs include 
payments by insurance, patients, and third parties. While this type of cost information is most accurate for our 
purposes, it is also the most difficult to obtain.   Recognizing the phenomenon of ‘upcharging,’ we will obtain 
hospital charges from each site as this is the easier data to acquire.   
H
SSU
H
SSU
E
E
C
C
ICER
−
−
=
KCCQ: 
Sample size 
(both arms 
combined) 
% of data 
attrition 
Difference 
in KCCQ 
change 
480 
10% 
5.3 
360 
33% 
6.2 
240 
55% 
7.6 
120 
78% 
10.7 

26 
SSU Protocol V6.0 9.20.2019 
Given the difficulty of obtaining costs and payments, we will standardize hospitalization and SSU costs using 
Medicare reimbursement rates (See Sensitivity Analysis Section below). Patient costs will include self-
reported out-of-pocket costs and time costs using a modified version of a previously published survey. (see 
attached) One limitation of self-reported data will be potential mismeasurement due to recall bias.  Should the 
patient-completed survey lack a sufficient response rate for outpatient analysis, we will limit our analysis to the 
hospital portion of the treatment.  Effectiveness will be defined by SF-12 and SF-6D metrics of patient self-
reported QOL.  The SF-12 has been previously used to evaluate outcomes for HF patients.3 Effectiveness in 
ICER computations is often measured using quality-adjusted life years (QALYs), defined as: 
 
where Pt is the probability of surviving to each year t, qt is the preference weight, and   is the time-discounting 
factor.  As the SF-12 does not allow direct assessment of QALYs, we will convert the score into a SF-6D 
preference based score using the six health dimension scores from the SF-124,5 to generate the preference 
weights and probabilities necessary to conduct the cost-utility analysis. Since the participant will be completing 
the SF-12 survey at the beginning and end of the episode, all models estimating the effectiveness will include 
the baseline score in the vector of participant characteristics.   Aside from cost and effectiveness, we will 
analyze the incidence of re-admission, the utilization of outpatient care, and caregiver burden, as detailed in 
our statistical analysis plan.  While the incidence of re-admission will be obtained from both the electronic 
health record and patient self-report, the outpatient and caregiver burden are self-reported.   
For each outcome variable of interest (patient costs, hospital costs, total episode costs, SF-12 scores, SF-6D 
scores, QALYs, incidence of readmission, total days of hospitalization, utilization of outpatient care, nursing 
care, and caregiver burden) we will estimate a predictive model accounting for the heterogeneity among 
participants in the intervention and control groups.   
 
where, Yi is the outcome of interest for participant i described in the following paragraph.  SSUi is an indicator 
if the participant was assigned to the SSU treatment, Di are the total number of hospital inpatient days, Ri is an 
indicator for a readmission.  The interaction terms Di*Ri  and Di*Ri*SSUi  differentiate between continuous 
inpatient days and inpatient days separated with a readmission, for hospital admission and SSU group 
respectively.  The interaction terms Di*SSUi, and Ri*SSUi capture the effect of SSU on inpatient days and 
readmission rates.  Xi is a vector of participant characteristics (age, gender, insurance status, etc.), Hh is a 
vector of hospital characteristics, h, t are hospital, and year fixed effects, and  i is an independent and 
identically distributed error term.  The effect of the SSU assignment on the outcome measure will be captured 
by coefficients 1, 5, 6, 7, unbiased and consistent estimators of the intervention effect because of the 
random assignment of participants.   
When estimating the re-admission rate, we will use a probabilistic model such as: 
 
where the probability of readmission will be a function of intervention status, SSUi, days of inpatient care, Di, 
the interaction between these, Di*SSUi, participant characteristics, Xi, vector of hospital characteristics, Hh , 
and fixed effects, h, t, and i is an independent and identically distributed error term. The choice of the 
functional form for this model will depend on the incidence of readmission in the data  

=
−
=
Z
t
t
t
t
t
t
P
q
QALY
0
0

i
t
h
h
i
i
i
i
i
i
i
i
i
i
i
i
i
i
H
X
SSU
R
D
SSU
R
SSU
D
R
D
R
D
SSU
Y













+
+
+
+
+


+

+

+

+
+
+
+
=
7
6
5
4
3
2
1
)
(
)
Pr(
3
2
1
i
t
h
h
i
i
i
i
i
i
H
X
SSU
D
D
SSU
F
R









+
+
+
+
+

+
+
+
=

27 
SSU Protocol V6.0 9.20.2019 
Random assignment to SSU will be tested in pre-analysis by comparing the means of the intervention and 
control group characteristics using t-tests, and probability of being assigned to intervention group conditional 
of participant characteristics, particularly health status. 
Sensitivity Analysis for CEA 
To test the robustness of our estimates, in view of the assumptions made about cost, the choice of 
effectiveness measure, and the probability specification function for readmission, we will re-evaluate our 
results with alternative definitions.  
To test the sensitivity of ICER to definition of cost, we will construct a projected cost measure based on CMS 
reimbursement for ICD-10 and CPT codes for hospitalization and SSU participants.  The benefits and 
shortcomings of this approach are outlined in Table 1. Should the SF-12 lack sufficient variability between 
SSU and hospitalized participants, converting the measure to SF-6D will reduce the remaining heterogeneity, 
magnifying the ICER cost estimate.  We will repeat ICER with SF-12 to test the significance in the loss of 
heterogeneity due to conversion.   
Table 1 Hospital Costs Reports 
 
Pros 
Cons 
1   Payments  
Payments 
received by 
hospitals from 
all sources 
• 
Most accurate reflection of 
costs of care. 
• 
Cost for all types of 
insurance 
• 
Includes patient share of 
cost 
• 
Hospitals reluctant to 
report 
• 
Does not include 
uncompensated care 
 
2   Reimbursements 
from CMS 
Payments 
from CMS for 
Medicare and 
Medicaid 
patients 
• 
Accurate reflection of costs 
of care. 
• 
Projected to non-CMS 
patients. 
• 
70% of all ED visits have 
Medicare or Medicaid as 
primary payer. 
• 
Obtain claims report from 
CMS (?) 
• 
Less accurate for non-
CMS patients. 
• 
Does not include patient 
share or uncompensated 
care. 
3  Charges 
Charges 
presented by 
hospital for 
each 
procedure 
• 
Procedure specific 
charges 
• 
Accurate reflection of the 
charges presented to 
insurance or CMS 
• 
Hospitals more likely to 
report 
• 
Includes all types of 
insurance, including 
uncompensated care. 
• 
Charges to cost ratio may 
differ by treatment type 
• 
Not an accurate reflection 
of the cost of care. 
• 
Does not include patient 
share. 
4   Projected costs 
By CPT and 
ICD-10 codes 
transformed 
• 
Approximate measure of 
CMS reimbursement 
• 
70% of all ED visits have 
Medicare or Medicaid as 
primary payer 
• 
Lost accuracy of variation 
in cost 
• 
Does not include patient 
share 
• 
Less accurate for non-
CMS patients 

28 
SSU Protocol V6.0 9.20.2019 
through CMS 
reimbursement 
rates. 
 
When analyzing the re-admission rates, we will use a multinomial binary logistic function, estimating the odds 
ratio of any re-admission as a function of SSU status.  We will also estimate the specification using a negative 
binomial generalized linear model with a log-link function, to analyze the effect of SSU on the number of re-
admissions. 
10.4.3.1 ADDITIONAL ANALYSES 
Exploratory Analyses: As observation is not an admission, payers cover out of pocket costs differently.  
Guideline Adherence: Adherence to HF guidelines at time of discharge in the SSU arm is equivalent or better than 
adherence in the usual care arm.  
Sample Size Calculation: We assume that the adherence percentage is 85% in the control arm.64 With 240 subjects in 
each arm, we will have 80% power to detect an absolute improvement of 
8% in the SSU arm, where the type I error rate is controlled at 0.05 (two-
sided). Adherence to HF-Guidelines will be assessed based on the 
established Get-With-The-Guidelines HF (GWTG-HF) metrics for eligible 
patients.  These measures have been previously well established.64,74   
HF Guideline Adherence Analysis:  Fisher’s exact test will be used to 
compare the percentage of adherence. Please see below regarding 
sensitivity analysis and missing data approaches.  
 
Caregiver Burden Analysis:  This will be similar to the KCCQ analysis. See table for sample size considerations. 
 
Sub-group analysis: The nature of the sub-group analysis is exploratory and will be used to generate hypotheses for future 
testing. We will study four pre-specified sub-groups: 1) older patients, defined as greater than 75 years old; 2) gender; 3) 
race and 4) insurance status (Medicaid, self-pay, Medicare, Commercial). The rationale for selecting these sub-groups is 
based either on known cardiovascular disparities or there is limited data regarding an SSU strategy in these specific 
subgroups.46 The hypothesis: there will be no differences in outcomes, QoL, or guideline adherence between any of these 
groups. If the primary endpoint is achieved, we aim to demonstrate the AHF SSU strategy is broadly applicable across all 
subgroups. If there are differences, however, this may either demonstrate areas in need of further study, or initial 
subgroups to target. To test these hypotheses, we will compare the treatment benefit between sub-groups by formal 
two-sample testing procedures using normal approximation (e.g. Z test). A permutation test will also be performed as a 
sensitivity analysis. Given the limited sample size and the exploratory nature of the sub-group analysis, no multiple 
comparison adjustment will be made for these tests.  
Intervention Monitoring: To ensure fidelity of each component of the intervention between study arms, we will also 
measure the following individual components of the intervention throughout the trial at both the site and overall study 
level: 1) Baseline patient characteristics, 2) Medicine reconciliation 3) Guideline-HF adherence 4) SSU AHF protocol 
adherence, 5) admission rates from the SSU 6) Quality of Life/Caregiver Burden Questionnaire response and 
completeness, 7) Hospitalized patients discharged within 48 hours, and 8) Follow up completed at 30 days. These 
analyses will be reported every 3 months to the Steering Committee to allow for course correction as needed. In 
addition, these will be reported at the conclusion of the study as well as at quarterly enrollment milestones to the 
DSMB. 
CB Scale: 
Sample size 
(both arms 
combined) 
% of data 
attrition 
Effect size 
in CB scale 
480 
10% 
0.25 
360 
33% 
0.30 
240 
55% 
0.37 
120 
78% 
0.51 

29 
SSU Protocol V6.0 9.20.2019 
Sensitivity Analyses: Some baseline covariates such as co-morbidities, medications, renal function, serum sodium, 
potassium, b-type natriuretic peptide (BNP) or NT-pro BNP, and blood pressure, may not be well-balanced between the 
two arms despite randomization. These covariates are known markers of risk in AHF patients and are part of the standard 
assessment for the vast majority of AHF admissions.  We will use the inverse probability weighting approach to adjust 
those covariates with poor balance between the arms as part of a sensitivity analysis.75 We will then compare these results 
with those from the two-sample t test.  In addition, if the DAOOH, QoL, caregiver burden, or mRUQ-HF endpoints are 
found to be non-normal in distribution, the Wilcoxon Rank-Sum test will be used for comparison as a sensitivity analysis.  
Modified Resource Utilization Questionnaire for Heart Failure (mRUQ-HF).70 The mRUQ-HF is a14-item self-report 
questionnaire of comprehensive lists of choice related to healthcare utilization. (See Appendix trial protocol)  
Exploratory analysis will occur in two steps: 1) Determination of resources consumed or related; 2) Assignment of 
‘value’ to the resources consumed.71  This two-step process allows for transparency of assigned costs.  Hospital costs 
will be assigned per individual hospital cost-accounting. Where monetary values are not directly self-reported, 
Medicare fee schedules will be used for uniformity.  This will be captured at 90 days and will include the hospitalization 
when patients answer the questionnaire. 
All Cause Mortality and All-Cause Rehospitalization Endpoints: 
A composite endpoint of all-cause mortality and re-hospitalization is defined as the time from the randomization to 
either all-cause death, or re-hospitalization.  The two intervention arms will be compared using a log-rank test.  Given 
the multiple hospitals, a stratified log rank test will be utilized. 
To compare the proportions of patients who had either all cause mortality or re-hosptialization within 30 days and 
separately 90 days from randomization, a composite endpoint of all-cause mortality and re-hospitalization is defined as 
either 1 for patients who died or re-hospitalized with 90 days since randomization, or 0 otherwise.  The two 
intervention arms will be compared using the Fisher’s exact test or Chi-square test as appropriate. 
 
10.4.4 SAFETY ANALYSES 
As all cause mortality and re-hospitalizations will already be reported as part of the efficacy exploratory analyses, these 
will also be highlighted as safety analyses.  We will also report the proportion of patients who are admitted from the 
SSU as well as AE/SAE’s. 
10.4.5 ADHERENCE AND RETENTION ANALYSES 
Missing data: This study does not anticipate significant missing data because the follow-up is fairly short. However, we 
have planned for this unlikely possibility in both our sample size calculations and analysis plan. The magnitude of any 
missing data and their relevant distributions will be properly documented. Multiple-imputation42 will be used to analyze 
the incomplete data under the assumption of missing at random (MAR).43 If it is of concern that the data may be 
missing not at random (MNAR),43 then a sensitivity analysis will be performed under multiple imputation scheme.44 
Summary data at baseline based on subjects with legitimate values on corresponding variables will be reported. For 
main inferential statistics, results based on the strategy of ignoring the missing data and multiple imputations will be 
reported so that the impact of missing data can be assessed. 
To ensure completeness, medical records will also be reviewed for items such as past medical history, lab results, 
medications, and other test results. The DCC will perform data audits at periodic intervals to assess the integrity of the 
data, also checking for missing data. Any fields with more than 5% missing data will be flagged for further investigation, 
with queries to sites to ascertain the reasons and/or fix accordingly. If needed, protocols or procedures will be 
implemented, along with further education, to minimize further missing data. In terms of drop-outs, a well-trained 
study team works to minimize this through careful screening and informed consent. While patients may withdraw their 
consent at any time, reasons for withdrawal will be queried and tabulated.  For patients who drop out, the reason for 
dropping out will be queried and recorded. These will be tabulated to determine if specific reasons for drop-outs are 
occurring, which will then be addressed by the Executive Committee. Every attempt to complete assessments for the 

30 
SSU Protocol V6.0 9.20.2019 
outcomes of interest to this study will be undertaken. In keeping with the pragmatic, simple nature of this trial design, 
there will be no clinical events or adjudication committee, as total DAAOH will be counted, irrespective of mode of 
death or re-hospitalization. 
10.4.6  Baseline Descriptive Statistics 
Patient baseline characteristics will be tabulated for both SSU and usual care groups. Specifically, means (standard 
deviations) or medians (interquartile range) will be presented for continuous variables such as age and body mass 
index. For categorical variables, such as gender and race, frequency and percentages will be presented. Group 
comparisons of continuous variables will be based on either two-sample t-tests (under normality) or Wilcoxon’s Rank 
Sum test. Normality of distribution will be determined using the Kolmogorov-Smirnov goodness-of-fit test. Categorical 
data comparisons will be presented based on the Chi-square or Fisher’s exact test. Standardized difference is used to 
compare the mean of the SSU and usual care groups.72  
10.4.7 PLANNED INTERIM ANALYSES  
Formal interim analysis will occur arfter 50% of patients have been accrued. NO formal stopping rules have been 
established, given the clinical effectiveness study design. IN other words, safety concerns are unlikely and equivalent 
outcomes would not be defined as futile. Rather, the DSMB will issue recommendations on halting the trial early, only 
for safety reasons, based on the totality of data reviewed. 
 
10.5 
SAMPLE SIZE 
A one-day difference in the length of hospital stay is a 20% reduction in the mean length of stay(LOS) of five days during 
hospitalization (median LOS =4.3 days).50 Pilot data support the clinical significance of a one-day reduction,45 and 
discussions with patients and caregivers confirms this finding. While we anticipate achieving greater than a one-day 
difference, we have powered our study conservatively. 
N (total) = 534;     N1 = 267;      N2 = 267 
Based on published data,46 we project that DAOOH has a mean of 25.6 with a standard deviation of 3.9 in the control 
arm. A reduction of the mean DAOOH by one-day is the minimal clinically meaningful difference as determined through 
our patient engagement outreach.54 An interim analysis when half of the outcome data are available will be performed. 
(See DSMB, section E6). Accounting for this with the O’Brien-Fleming spending function, 240 subjects per arm are 
required to achieve 80% power in detecting the one-day difference in DAOOH, where the two-sided type I error rate is 
controlled at 0.05. Assuming 10% attrition due to drop-outs and lost to follow up, this study requires a total of 534 
subjects.  This power calculation also takes into account a conservative estimate of 40% of patients being admitted to 
the hospital from the SSU arm. DAOOH automatically accounts for death. The maximal number of days alive and out of 
the hospital through 30 days post randomization is 30 days.  If a patient were to die on day 8 post-randomization, her 
DAOOH would be 8.  This would be compared to a patient who stayed in the hospital 3 days after randomization, but 
never returned to the ED or hospital or died through 30 days.  DAAOH of this patient would be 27.  If the same patient 
returned to the hospital on day 12 for 2 days, and again on day 24 for 2 days, their total DAOOH would be 23.  
10.6 
MEASURES TO MINIMIZE BIAS 
10.6.1 ENROLLMENT/ RANDOMIZATION/ MASKING PROCEDURES 
Patients will be randomized 1:1 to one of the two study arms, but stratified by site to ensure equal site representation. 
A central computer generated randomization scheme with random block sizes of two, four, and six will be created, 
stratified by site. The REDCap randomization module will be utilized to generate the randomization schema and patient 
allocation. 
Due the nature of the intervention and the clinical setting, this is an unblinded trial. 
11 
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS 

31 
SSU Protocol V6.0 9.20.2019 
The medical experts, study monitors, auditors, and health authority inspectors (or their agents) will be given direct 
access to source data and documentation (e.g., medical charts/records, laboratory test results, printouts, videotapes) 
for source data verification, provided that patient confidentiality is maintained in accordance with local requirements. 
Each Investigator must maintain, at all times, the primary records (i.e., source documents) of each patient’s data.  
Examples of source documents are hospital records, office visit records; examining physician’s finding or notes, 
consultant’s written opinion or notes, laboratory reports, drug inventory, study drug label records, and CRFs that are 
used as the source. 
Each Investigator will maintain a confidential patient identification list that allows the unambiguous identification of 
each patient.  All study-related documents must be kept for a minimum of 5 years.  A publically available dataset will be 
released per NIH guidelines. 
12 
QUALITY ASSURANCE AND QUALITY CONTROL 
Protocol Amendments: No changes from the final approved (signed) protocol will be initiated without the prior written 
approval or favorable opinion of a written amendment by the IEC/IRB, except when necessary to eliminate immediate 
safety concerns to the patients or when the change involves only logistics or administration.  Each Investigator will sign 
the protocol amendment.  
The IRB/EC may provide expedited review and approval/favorable opinion for minor change(s) in ongoing studies.  
Protocol Deviations, Violations, and Exceptions:  A protocol deviation is non-adherence to protocol-specific study 
procedures or schedules that does not involve inclusion/exclusion criteria, primary objective variable criteria, and/or 
GCP guidelines.  Deviations are considered minor and do not impact the study. 
A protocol violation is any significant divergence from the protocol, i.e., non-adherence on the part of the patient, the 
Investigator, or the sponsor to protocol-specific inclusion/exclusion criteria, primary objective variable criteria, and/or 
GCP guidelines.  Protocol violations will be identified and recorded, by study center personnel. 
No exceptions to protocol-specific entry criteria will be granted to allow patients to enter a study.   
Information to Study Personnel: Each Investigator is responsible for giving information about the study to all staff 
members involved in the study or in any element of patient management, both before starting the practical 
performance of the study and during the course of the study (e.g., when new staff become involved).  Each Investigator 
must assure that all study staff members are qualified by education, experience, and training to perform their specific 
responsibilities.  These study staff members must be listed on the study center authorization form, (if required) which 
includes a clear description of each staff member’s responsibilities.  This list must be updated throughout the study, as 
necessary. 
The study monitor is responsible for explaining the protocol to all study staff, including each Investigator, and for 
ensuring their compliance with the protocol.  Additional information will be made available during the study when new 
staff become involved in the study and as otherwise agreed upon with either the Investigator or the study monitor. 
The handling of data, including data quality assurance, will comply with regulatory guidelines (e.g., ICH and GCP) and 
the sponsor’s or its designee’s SOPs and working instructions.  Data management and control processes specific to this 
study will be described in a data management plan.  When data management is outsourced, the contract organization 
will be responsible for the development and implementation of the data management plan.  
Data Quality Assurance: All data on the CRF will be entered into a validated database compliant with 21 CFR Part 11 
requirements.  In the case when data management is outsourced, the contract organization will be responsible for 
database quality assurance including, but not limited to, review of data entered into the CRFs by study center personnel 
for completeness and accuracy and instruction of the study personnel to make any required corrections. 
Data management at Indiana University will implement edit checks on the eCRF to enforce data integrity and 
compliance to the protocol and regulatory requirements.  Study center personnel will be responsible for entering study 
data on the eCRFs.  Data management will track eCRFs and review them for completeness, the presence of mandatory 
values, consistency, and dated electronic signatures.  Queries identified during data discrepancy review will be sent to 
the study center personnel to be reviewed and resolved in a timely manner. 

32 
SSU Protocol V6.0 9.20.2019 
Adverse Events will be coded using the MedDRA dictionary.  Concomitant medications will be coded using the WHO 
Drug dictionary.  Adverse Events and Concomitant Medications will be reviewed for coding consistency and 
completeness.  
At the end of the study, the database will be locked and the data will be released for reporting and statistical analysis. 
13 
ETHICS/PROTECTION OF HUMAN SUBJECTS  
13.1 
ETHICAL STANDARD  
The Investigator(s) will conduct the study in accordance with this protocol, the guiding principles of the Declaration of 
Helsinki, ICH GCP guidelines and applicable regulatory requirements.   
13.2 
INSTITUTIONAL REVIEW BOARD  
Before this study starts, the protocol will be submitted to each IEC/IRB for review.  As required, the study will not start 
at a given center before the IEC/IRB for the center provides written approval or a favorable opinion. The IRB will meet 
all FDA requirements governing IRBs (Code of Federal Regulations, Title 21, Part 56).  The IEC will meet local regulations. 
13.3 
INFORMED CONSENT PROCESS  
13.3.1 CONSENT/ASSENT AND OTHER INFORMATIONAL DOCUMENTS PROVIDED TO PARTICIPANTS 
Each patient must be provided with a statement that the investigation involves research and that the IRB/EC has 
approved solicitation of patients to participate; a fair explanation of the procedures to be followed and their purposes, 
including identification of any procedures which are experimental; a description in lay language of any possible side 
effects; a description of any attendant discomforts and risks reasonably to be expected; a description of any benefits 
reasonably to be expected; a disclosure of any appropriate alternative procedures that might be advantageous for the 
patient; an offer to answer any inquiries concerning the procedures, and instruction that the person is free to withdraw 
consent and discontinue participation in the project or activity at any time without prejudice to the patient.  The 
informed consent shall include a disclosure that the Investigator is being supported by the NIH to perform the stated 
research. 
13.3.2 CONSENT PROCEDURES AND DOCUMENTATION 
A properly executed, written consent in compliance with current U.S. federal code 21CFR part 50, or competent 
regulatory authority, shall be obtained from each patient prior to entering the study or prior to performing any unusual 
or non-routine procedure involving risk to the patient.   
A patient must give written consent to participate in the study.  This consent must be dated and retained by the 
Principal Investigator as part of the study records.  A copy shall be given to the patient.  The informed consent process 
must be documented in the patient’s source documents. 
Written and/or oral information about the study in a language understandable by the patient will be given to all 
patients. 
13.4 
PARTICIPANT AND DATA CONFIDENTIALITY  
Each Investigator must assure that the privacy and confidentiality of each study  patient’s, personal identity and 
personal medical information is, maintained at all times.  In order to maintain subject privacy and confidentiality, all 
CRFs, laboratory specimens, evaluation forms, reports, and other records, documents and image material that leave the 
site will be identified only by an identification code.  This identification code shall on no occasion include study subject’s 
names, initials or date of birth.  
Personal medical information may release or review the personal health data of study patients shall take place solely 
within circumstance, and to third parties, specifically identified by the written informed consent document signed by 
the study patients, except as permitted by applicable laws and regulations for purposes of monitoring and data 
verification by the relevant regulatory authorities, the NIH and NIH’s properly authorized representatives, the quality 
assurance unit, or regulatory authorities.  Personal medical information will always be treated as confidential. 
14 
DATA HANDLING AND RECORD KEEPING  

33 
SSU Protocol V6.0 9.20.2019 
14.1 
DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES  
Each Investigator must keep a separate patient identification list showing code numbers, names, and dates of birth to 
allow unambiguous identification of each patient included in the study.  A note will be made in the medical records that 
the patient is participating in a clinical study. 
All required data will be recorded on the CRF by study center personnel according to the data entry guidelines provided 
by the PI or designee.  All CRFs must be kept in good order and updated so they always reflect the latest observations 
on the patients participating in the study. 
When paper CRFs are used, they will be completed legibly in black ink, with reasons given for missing data.  Any 
corrections to the data will be made in a manner that does not obscure the original entry and will be dated and initialed 
by the Investigator or assigned designee.  Each Investigator will sign the statement on the last page of the CRF. 
When eCRFs are used, electronic signatures of the Investigator (or designee) will be provided.   
Access to the eCRF for data entry and signature is controlled by user identification and password, which are provided by 
the PI or designee.  Study center personnel will be trained, by the PI or designee, in the use of eCRFs and application of 
electronic signatures before the start of the study. 
Because it is extremely important to have proper data collection in a timely manner, the Investigator shall complete the 
CRFs and on an ongoing basis.  If a study monitor is needed and study monitor requests additional data or clarification 
of data for the CRF, the request must be answered satisfactorily in a timely manner before the next monitoring visit. 
14.2 
STUDY RECORDS RETENTION  
All records related to the study (i.e., source data, source documents, CRFs, copies of protocols and protocol 
amendments, correspondence, patient identification lists, signed informed consent forms, and other essential 
documents) must be retained for a minimum of 5 years. 
Should an Investigator wish to assign the study records to another party or move them to another location, advance 
written notice will be given to the PI and NIH. 
The Investigator will maintain all study records according to International Conference on Harmonization (ICH)-GCP and 
applicable regulatory requirements.  Records will be retained for two (2) years following the date a marketing 
application is approved for the indication pertaining to this clinical study; or, if the medication is planned to be 
terminated or if a Regulatory application is not planned to be progressed, until two (2) years after the investigation is 
discontinued and the Food and Drug Administration (FDA), or competent regulatory authority, is notified. 
14.3 
PROTOCOL DEVIATIONS  
A protocol deviation is non-adherence to protocol-specific study procedures or schedules that does not involve 
inclusion/exclusion criteria, primary objective variable criteria, and/or GCP guidelines.  Deviations are considered minor 
and do not impact the study. 
A protocol violation is any significant divergence from the protocol, i.e., non-adherence on the part of the patient, the 
Investigator, or the sponsor to protocol-specific inclusion/exclusion criteria, primary objective variable criteria, and/or 
GCP guidelines.  Protocol violations will be identified and recorded, by study center personnel. 
No exceptions to protocol-specific entry criteria will be granted to allow patients to enter a study.   
14.4 
PUBLICATION AND DATA SHARING POLICY 
RESOURCE SHARING, DISSEMINATION, AND DATA SHARING PLAN 
This includes the following activities: 
▪ 
Publicizing the study as it is initiated, to trial investigators and other interested researchers 
▪ 
Identifying and supporting proposals, (funding sources, implementation, analyses) for feasible salient ancillary 
studies; 
▪ 
Providing a fully anonymized data set for future analyses/studies by interested researchers, once the trial 
funding has ended. 

34 
SSU Protocol V6.0 9.20.2019 
Each of these activities is discussed below.  
Publicizing the Study 
The key methods for publicizing the trial are: 
▪ 
ClinicalTrials.gov – the government website that registers all initiated trials with trial protocol descriptions and 
contact information; 
▪ 
The trial site PI's and involved leadership group 
▪ 
Design and rationale paper will be submitted for publication 
Providing Access to Linked, Anonymized Data  
Once trial funding ends, two options will be: 
▪ 
Provide the anonymized data set to AHRQ, if desired 
▪ 
Maintain the linked, anonymized data set via the IU Data Coordinating Center. 
Regardless of which option is implemented, information on availability of data will be accessible on ClinicalTrials.gov 
and will be linked to other appropriate sites, including Indiana University websites. 
PREPARATION OF THE ANONYMIZED, LIMITED ACCESS DATASET 
We propose the following activities for the data set: 
1. Subject identifiers: 
a. New random identification numbers without site identifiers will replace the original identification 
numbers, once data acquisition is complete. 
b. The key linking the original and new ID numbers will NOT be provided to users of the anonymized data 
set, nor to site investigators and staff. 
2. Variables that might lead to the identification of participants: 
a. Interviewer or technician identification numbers or codes will be recoded or deleted. 
b. Regional variables with little or no variation within a center because they could be used to identify the 
center will be deleted. 
c. Unedited, verbatim responses that are stored as text data (e.g., specified in “other” category) will be 
deleted. 
3. Dates: All dates will be coded relative to a specific reference point (e.g., date of randomization). This provides 
privacy protection for individuals known to be in a study who are known to have had some significant event 
(e.g., myocardial infarction) on a particular date. Birth and other milestone dates will also be recoded relative to 
a specific reference date. 
4. Variables with low frequencies for some values, that might be used to identify participants, may be recoded. 
These might include: 
a. Socioeconomic and demographic data (e.g., marital status, occupation, income, education, language, 
number of years married). 
b. Household and family composition (e.g., number in household, number of siblings or children, ages of 
children or step-children, number of brothers and sisters, relationships, spouse in study). 
c. Numbers of pregnancies, births, or multiple children within a birth. 
d. Anthropometry measures (e.g., height, weight, waist girth, hip girth, body mass index). 
e. Physical characteristics that are distinctive (e.g., blindness). 
f. Prior medical conditions with low frequency (e.g., group specific cancers into broader categories) and 
related questions such as age at diagnosis and current status. 
5. Race/ethnicity and gender information when very few subjects are in certain groups or cells. 

35 
SSU Protocol V6.0 9.20.2019 
a. Polychotomous variables: values or groups will be collapsed so as to ensure a minimum number of 
subjects (e.g., at least 20) for each value within each race-gender cell. 
b. Continuous variables: distributions will be truncated if needed to ensure that a minimum number of 
subjects (e.g., at least 20) have the same highest and lowest values in each race-gender cell. 
c. Dichotomous variables: data should either be grouped with other related variables so as to ensure a 
minimum number of subjects (e.g., at least 20) in each race-gender cell or deleted. 
This includes the following activities: 
▪ 
Publicizing the study as it is initiated, to trial investigators and other interested researchers 
▪ 
Identifying and supporting proposals, (funding sources, implementation, analyses) for feasible salient ancillary 
studies; 
▪ 
Providing a fully anonymized data set for future analyses/studies by interested researchers, once the trial 
funding has ended. 
Each of these activities is discussed below.  
Publicizing the Study 
The key methods for publicizing the trial are: 
▪ 
ClinicalTrials.gov – the government website that registers all initiated trials with trial protocol descriptions and 
contact information; 
▪ 
The trial site PI's and involved leadership group 
▪ 
Design and rationale paper will be submitted for publication 
▪ 
A final manuscript will be submitted after conclusion of the study. 
Providing Access to Linked, Anonymized Data  
Once trial funding ends, two options will be: 
▪ 
Provide the anonymized data set to AHRQ.  
▪ 
Maintain the linked, anonymized data set via the IU Data Coordinating Center. 
Regardless of which option is implemented, information on availability of data will be accessible on ClinicalTrials.gov 
and will be linked to other appropriate sites, including Indiana University websites. 
PREPARATION OF THE ANONYMIZED, LIMITED ACCESS DATASET 
To comply with NIH requirements for an adequately anonymized dataset, we propose the following activities for the 
data set: 
6. Subject identifiers: 
a. New random identification numbers without site identifiers will replace the original identification 
numbers, once data acquisition is complete. 
b. The key linking the original and new ID numbers will NOT be provided to users of the anonymized data 
set, nor to site investigators and staff. 
7. Variables that might lead to the identification of participants: 
a. Interviewer or technician identification numbers or codes will be recoded or deleted. 
b. Regional variables with little or no variation within a center because they could be used to identify the 
center will be deleted. 
c. Unedited, verbatim responses that are stored as text data (e.g., specified in “other” category) will be 
deleted. 
8. Dates: All dates will be coded relative to a specific reference point (e.g., date of randomization). This provides 
privacy protection for individuals known to be in a study who are known to have had some significant event 

36 
SSU Protocol V6.0 9.20.2019 
(e.g., myocardial infarction) on a particular date. Birth and other milestone dates will also be recoded relative to 
a specific reference date. 
9. Variables with low frequencies for some values, that might be used to identify participants, may be recoded. 
These might include: 
a. Socioeconomic and demographic data (e.g., marital status, occupation, income, education, language, 
number of years married). 
b. Household and family composition (e.g., number in household, number of siblings or children, ages of 
children or step-children, number of brothers and sisters, relationships, spouse in study). 
c. Numbers of pregnancies, births, or multiple children within a birth. 
d. Anthropometry measures (e.g., height, weight, waist girth, hip girth, body mass index). 
e. Physical characteristics that are distinctive (e.g., blindness). 
f. Prior medical conditions with low frequency (e.g., group specific cancers into broader categories) and 
related questions such as age at diagnosis and current status. 
10. Race/ethnicity and gender information when very few subjects are in certain groups or cells. 
a. Polychotomous variables: values or groups will be collapsed so as to ensure a minimum number of 
subjects (e.g., at least 20) for each value within each race-gender cell. 
b. Continuous variables: distributions will be truncated if needed to ensure that a minimum number of 
subjects (e.g., at least 20) have the same highest and lowest values in each race-gender cell. 
c. Dichotomous variables: data should either be grouped with other related variables so as to ensure a 
minimum number of subjects (e.g., at least 20) in each race-gender cell or deleted. 
CLINICAL TRIALS.GOV 
This study will be registered at the appropriate and required time by the PI, in conjunction with the DCC, to the 
government-operated clinical trial registry data bank, which contains registration, results, and other information about 
registered clinical trials at ClinicalTrials.gov. Federal law under FDAAA requires clinical trial information for certain 
clinical trials to be submitted to the data bank and this study will comply with all reporting requirements for clinical 
trials. 
15 
STUDY ADMINISTRATION 
15.1 
STUDY LEADERSHIP 
This study will be conducted at 3 sites in the United States, with 4 total hospitals.  Site 1) Indianapolis, IN at both the 
Eskenazi and Methodist hospitals (abbreviated as IU, Peter S. Pang, PI), Site 2) Nashville, TN at the University of 
Vanderbilt hospital (abbreviated as Vanderbilt, Sean P. Collins, PI), Site 3) Detroit, MI at the Detroit Receiving Hospital 
Center (abbreviated as DRC, Philip D. Levy.  Each site PI will be a member of the steering committee.  Dr. Susan Pressler 
will also be a member of the steering committee.  Dr. Sean Collins will chair the steering committee.  
   
 

37 
SSU Protocol V6.0 9.20.2019 
 
 
Communication with DSMB members will be primarily through the AHRQ Program Office and the Data Coordinating 
Center (DCC) housed at IU.  The primary coordinator of data transfer between the research team and the DSMB will be 
the DCC working with the DSMB statistician, who will also be at IU.   It is expected that study investigators will not 
communicate with DSMB members about the study directly, except when making presentations or responding to 
questions at DSMB meetings or during conference calls.   
 
16 
CONFLICT OF INTEREST POLICY 
All investigators must adhere to national, regional, and local conflict of interest policies.  Prior to publication, all 
disclosures potentially relevant to this trial will be explicitly stated. 
17 
SURVEYS AND QUESTIONNAIRES 
17.1 
KCCQ 
 
17.2 
CAREGIVER BURDEN SCALES 
 
OBERST CAREGIVING BURDEN SCALE 
This group of questions is about the tasks and activities that you do to help the patient at home.  For each of 
the following activities, please mark how much time you spend and how difficult each activity is for you to 
do.   
New KCCQ.pdf

38 
SSU Protocol V6.0 9.20.2019 
 
1. Medical or nursing treatments (giving medications, skin care, dressings, etc.): 
Time you spend: 
 
 
How difficult: 
 
 
___ A great amount (5) 
 
___ Extremely difficult (5) 
 
 
___ A large amount (4) 
 
___ Very difficult (4) 
 
 
___ A moderate amount (3)  
___ Moderately difficult (3) 
 
 
___ A small amount (2) 
 
___ Slightly difficult (2) 
 
 
___ None (1)  
 
 
___ Not difficult (1) 
 
 
 
___About how many hours/day 
 
 
 
 
___About how many hours/week 
2.  Personal care (bathing, toileting, getting dressed, feeding, etc.): 
Time you spend: 
 
 
How difficult: 
 
 
___ A great amount (5) 
 
___ Extremely difficult (5) 
 
 
___ A large amount (4) 
 
___ Very difficult (4) 
 
 
___ A moderate amount (3)  
___ Moderately difficult (3) 
 
 
___ A small amount (2) 
 
___ Slightly difficult (2) 
 
 
___ None (1)  
 
 
___ Not difficult (1) 
 
 
 
 
 
___About how many hours/day 
 
 
 
 
___About how many hours/week 
                                                                                                                                                    
 
3. Managing dietary needs of the patient (planning and cooking meals, monitoring salt 
intake, etc.): 
 
Time you spend: 
 
 
How difficult: 
 
 
___ A great amount (5) 
 
___ Extremely difficult (5) 
 
 
___ A large amount (4) 
 
___ Very difficult (4) 
 
 
___ A moderate amount (3)  
___ Moderately difficult (3) 

39 
SSU Protocol V6.0 9.20.2019 
 
 
___ A small amount (2) 
 
___ Slightly difficult (2) 
 
 
___ None (1)  
 
 
___ Not difficult (1) 
 
 
 
 
___About how many hours/day 
 
 
 
 
___About how many hours/week 
 
4. Assistance with walking, getting in and out of bed, exercises, etc.: 
 SPEND: 
 
Time you spend: 
 
 
How difficult: 
 
 
___ A great amount (5) 
 
___ Extremely difficult (5) 
 
 
___ A large amount (4) 
 
___ Very difficult (4) 
 
 
___ A moderate amount (3)  
___ Moderately difficult (3) 
 
 
___ A small amount (2) 
 
___ Slightly difficult (2) 
 
 
___ None (1)  
 
 
___ Not difficult (1) 
 
 
 
 
 
___About how many hours/day 
 
 
 
 
___About how many hours/week 
 
 
5. Emotional support, “being there” for the patient: 
TIME YOU SPEND: 
 
 
 
HOW DIFFICULT: 
Time you spend: 
 
 
How difficult: 
 
 
___ A great amount (5) 
 
___ Extremely difficult (5) 
 
 
___ A large amount (4) 
 
___ Very difficult (4) 
 
 
___ A moderate amount (3)  
___ Moderately difficult (3) 
 
 
___ A small amount (2) 
 
___ Slightly difficult (2) 
 
 
___ None (1)  
 
 
___ Not difficult (1) 
 
 
 
___About how many hours/day 
 
 
 
 
___About how many hours/week 

40 
SSU Protocol V6.0 9.20.2019 
 
6. Watching for and reporting the patient’s symptoms, watching how the patient is doing, monitoring the 
patient’s progress: 
TIME YOU SPEND: 
 
 
 
HOW DIFFICULT: 
Time you spend: 
 
 
How difficult: 
 
 
___ A great amount (5) 
 
___ Extremely difficult (5) 
 
 
___ A large amount (4) 
 
___ Very difficult (4) 
 
 
___ A moderate amount (3)  
___ Moderately difficult (3) 
 
 
___ A small amount (2) 
 
___ Slightly difficult (2) 
 
 
___ None (1)  
 
 
___ Not difficult (1) 
 
___About how many hours/day 
 
___About how many hours/week 
 
7. Providing transportation or “company” (driving, riding along with patient, going to appointments, driving 
patient around for errands, etc.): 
Time you spend: 
 
 
How difficult: 
 
 
___ A great amount (5) 
 
___ Extremely difficult (5) 
 
 
___ A large amount (4) 
 
___ Very difficult (4) 
 
 
___ A moderate amount (3)  
___ Moderately difficult (3) 
 
 
___ A small amount (2) 
 
___ Slightly difficult (2) 
 
 
___ None (1)  
 
 
___ Not difficult (1) 
 
 
___About how many hours/day 
 
 
 
 
___About how many hours/week 
8. Managing finances, bills, and forms related to the patient’s illness: 
 
Time you spend: 
 
 
How difficult: 
 
 
___ A great amount (5) 
 
___ Extremely difficult (5) 
 
 
___ A large amount (4) 
 
___ Very difficult (4) 
 
 
___ A moderate amount (3)  
___ Moderately difficult (3) 
 
 
___ A small amount (2) 
 
___ Slightly difficult (2) 

41 
SSU Protocol V6.0 9.20.2019 
 
 
___ None (1)  
 
 
___ Not difficult (1) 
 
 
 
___About how many hours/day 
 
 
 
 
___About how many hours/week 
 
9. Additional household tasks for the patient (laundry, cooking, cleaning, yard work, home repairs, etc.): 
TIME YOU SPEND: 
 
 
 
HOW DIFFICULT: 
Time you spend: 
 
 
How difficult: 
 
 
___ A great amount (5) 
 
___ Extremely difficult (5) 
 
 
___ A large amount (4) 
 
___ Very difficult (4) 
 
 
___ A moderate amount (3)  
___ Moderately difficult (3) 
 
 
___ A small amount (2) 
 
___ Slightly difficult (2) 
 
 
___ None (1)  
 
 
___ Not difficult (1) 
 
 
 
___About how many hours/day 
 
 
 
 
___About how many hours/week 
 
 
 
Additional tasks outside the home for the patient (shopping for food and clothes, going to the bank, running 
errands, etc.): 
Time you spend: 
 
 
How difficult: 
 
 
___ A great amount (5) 
 
___ Extremely difficult (5) 
 
 
___ A large amount (4) 
 
___ Very difficult (4) 
 
 
___ A moderate amount (3)  
___ Moderately difficult (3) 
 
 
___ A small amount (2) 
 
___ Slightly difficult (2) 
 
 
___ None (1)  
 
 
___ Not difficult (1) 
 
 
 
___About how many hours/day 
 
 
 
 
___About how many hours/week 
 
10. Structuring/planning activities for the patient (recreation, rest, meals, things for the patient to do, etc.): 

42 
SSU Protocol V6.0 9.20.2019 
TIME YOU SPEND: 
 
 
 
HOW DIFFICULT: 
Time you spend: 
 
 
How difficult: 
 
 
___ A great amount (5) 
 
___ Extremely difficult (5) 
 
 
___ A large amount (4) 
 
___ Very difficult (4) 
 
 
___ A moderate amount (3)  
___ Moderately difficult (3) 
 
 
___ A small amount (2) 
 
___ Slightly difficult (2) 
 
 
___ None (1)  
 
 
___ Not difficult (1) 
 
 
 
___About how many hours/day 
 
 
 
 
___About how many hours/week 
 
 
11.  Managing behavior problems in terms of the patient’s moodiness and irritability: 
TIME YOU SPEND: 
 
 
 
HOW DIFFICULT: 
Time you spend: 
 
 
How difficult: 
 
 
___ A great amount (5) 
 
___ Extremely difficult (5) 
 
 
___ A large amount (4) 
 
___ Very difficult (4) 
 
 
___ A moderate amount (3)  
___ Moderately difficult (3) 
 
 
___ A small amount (2) 
 
___ Slightly difficult (2) 
 
 
___ None (1)  
 
 
___ Not difficult (1) 
 
 
 
 
___About how many hours/day 
 
 
 
 
___About how many hours/week 
 
12.  Managing behavior problems in terms of the patient’s memory loss, concentration, and attention: 
 
Time you spend: 
 
 
How difficult: 
 
 
___ A great amount (5) 
 
___ Extremely difficult (5) 
 
 
___ A large amount (4) 
 
___ Very difficult (4) 
 
 
___ A moderate amount (3)  
___ Moderately difficult (3) 
 
 
___ A small amount (2) 
 
___ Slightly difficult (2) 

43 
SSU Protocol V6.0 9.20.2019 
 
 
___ None (1)  
 
 
___ Not difficult (1) 
 
 
 
___About how many hours/day 
 
 
 
 
___About how many hours/week 
 
13.  Managing behavior problems in terms of the patient’s confusion, disorientation, or dementia: 
 
Time you spend: 
 
 
How difficult: 
 
 
___ A great amount (5) 
 
___ Extremely difficult (5) 
 
 
___ A large amount (4) 
 
___ Very difficult (4) 
 
 
___ A moderate amount (3)  
___ Moderately difficult (3) 
 
 
___ A small amount (2) 
 
___ Slightly difficult (2) 
 
 
___ None (1)  
 
 
___ Not difficult (1) 
 
 
 
___About how many hours/day 
 
 
 
 
___About how many hours/week 
 
 
 
14.  Finding and arranging someone to care for the patient while you are away: 
 
Time you spend: 
 
 
How difficult: 
 
 
___ A great amount (5) 
 
___ Extremely difficult (5) 
 
 
___ A large amount (4) 
 
___ Very difficult (4) 
 
 
___ A moderate amount (3)  
___ Moderately difficult (3) 
 
 
___ A small amount (2) 
 
___ Slightly difficult (2) 
 
 
___ None (1)  
 
 
___ Not difficult (1) 
 
 
 
___About how many hours/day 
 
 
 
 
___About how many hours/week 

44 
SSU Protocol V6.0 9.20.2019 
 
 Communication (helping the patient with the phone, writing or reading, explaining things, etc): 
 
Time you spend: 
 
 
How difficult: 
 
 
___ A great amount (5) 
 
___ Extremely difficult (5) 
 
 
___ A large amount (4) 
 
___ Very difficult (4) 
 
 
___ A moderate amount (3)  
___ Moderately difficult (3) 
 
 
___ A small amount (2) 
 
___ Slightly difficult (2) 
 
 
___ None (1)  
 
 
___ Not difficult (1) 
 
 
 
___About how many hours/day 
 
 
 
 
___About how many hours/week 
 
 
15. Coordinating, arranging, and managing services and resources for the patient (scheduling appointments, 
arranging transportation, locating equipment and services, and finding outside help): 
 
Time you spend: 
 
 
How difficult: 
 
 
___ A great amount (5) 
 
___ Extremely difficult (5) 
 
 
___ A large amount (4) 
 
___ Very difficult (4) 
 
 
___ A moderate amount (3)  
___ Moderately difficult (3) 
 
 
___ A small amount (2) 
 
___ Slightly difficult (2) 
 
 
___ None (1)  
 
 
___ Not difficult (1) 
 
 
 
___About how many hours/day 
 
 
 
 
___About how many hours/week 
 
 
16. Seeking information and talking with doctors, nurses, and other professional health care workers about the 
patient’s condition and treatment plans: 
 

45 
SSU Protocol V6.0 9.20.2019 
Time you spend: 
 
 
How difficult: 
 
 
___ A great amount (5) 
 
___ Extremely difficult (5) 
 
 
___ A large amount (4) 
 
___ Very difficult (4) 
 
 
___ A moderate amount (3)  
___ Moderately difficult (3) 
 
 
___ A small amount (2) 
 
___ Slightly difficult (2) 
 
 
___ None (1)  
 
 
___ Not difficult (1) 
 
 
 
___About how many hours/day 
 
 
 
 
___About how many hours/week 
 
 
 
 
 
 
 
 
 
 
Bakas Caregiving Outcomes Scale (BCOS) 
 
Site Specific ID or MRN 
Page 1 of 2 
 
Was a caregiver identified? Defined as person either                          No 
self-identifies, or when asked identifies                                           Yes 
themselves, as the primary caregiver for the 
patient. 
 
Person who filled out form                                                                      Caregiver filled out the form 
Research staff Asked the caregiver in person 
Research staff Asked thecaregiver by phone 
 
This group of questions is about the possible changes in your life from providing care for your family member or 
loved one. For each possible change listed, circle one number indicating the degree of change. The numbers 
indicating the degree of change range from 3 Changed for the Worst to +3 Changed for the Best. The number 0 
means Did Not Change. 
 
1. My self esteem 
 
2. My physical health 
 
3. My time for family activities 
 
4. My ability to cope with stress 
 
5. My relationship with friends 
 
6. My future outlook 
 
7. My level of energy 

46 
SSU Protocol V6.0 9.20.2019 
 
8. My emotional well-being 
 
9. My roles in life 
 
10. My time for social activities with friends 
 
-3 Changed for the Worst 
 
-2                  -1            0 Did Not Change 
 
1                   2           3 Changed for the Best 
 
11. My relationship with my 
family 
 
12. My financial well-being 
 
13. My relationship with the 
heart failure patient 
 
14. My physical functioning 
 
15. My general health 
 
16. In general, how has your life 
changed as a result of taking 
care of the heart failure 
patient? 
 
If there any other changes in your life as a result of providing care, please write them below and rate them 
accordingly. 
 
17 Description 

 
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1 
11/27/2017 5:38pm                                                                                                                       www.projectredcap.org 
Confidential 
Page 2 of 2 
 
17 Rating                                                                                               -3 Changed for the Worst 
-2 
-1 
0 Did Not Change 1 
2 
3 Changed for the Best 
 
18 Description 
 
18 Rating                                                                                               -3 Changed for the Worst 
-2 
-1 
0 Did Not Change 1 
2 
3 Changed for the Best 
 
19 Description 
 
19 Rating                                                                                               -3 Changed for the Worst 
-2 
-1 
0 Did Not Change 1 
2 
3 Changed for the Best 
 
OBERST CAREGIVING 
BURDEN SCALE.docx
BCOS120715 -
modified HF.doc
 
17.3 
MRUQ-HF 
 
MODIFIED RESOURCE UTILIZATION QUESTIONNAIRE FOR HEART FAILURE  
(SOCIETAL PERSPECTIVE) 
 
This is a series of questions about your health care that you have received during past 3 months. 
 
1. During the past 3 months, how many times have you had appointments or visits at any of the following 
clinics or providers? 
Clinics / Providers 
Number of 
Appointments/Visits 
How Long 
(hours) 
Reason for 
Appointments/Visits 
Cardiologist 
 
 
 
Home health services 
 
 
 

 
Version <4.0> 
 
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2 
Nurse clinic visit 
 
 
 
Emergency department 
 
 
 
Hospitalization 
 
 
 
Other healthcare appointments 
 
 
 
Endocrinologist 
 
 
 
Nephrologist 
 
 
 
Ophthalmologist 
 
 
 
Allergist/Ear Nose Throat clinic 
 
 
 
Alternative/ 
homeopathic medicine 
 
 
 
Chiropractor 
 
 
 
Dentist 
 
 
 
Dermatologist 
 
 
 
Family physician/ 
internal medicine/ 
primary care physician 
 
 
 
Gastroenterologist 
 
 
 
Mental health professional 
 
 
 
Orthopedist 
 
 
 
Physical therapist 
 
 
 
Physician assistant 
 
 
 
Podiatrist 
 
 
 
Other:         
 
 
 
 
2. Not including the visits just listed, during the past 3 months, how many times did you communicate 
(telephone, e-mail, text, fax) with anyone (physician, nurse, or technical support) regarding your heart 
condition? 
 
 
Reason for contact 
Number of contacts 
for information 
needed or 
communication 
Type of 
communication 
(phone, e-mail, etc) 
Physician 
 
 
 
Nurse practitioner 
 
 
 
Nurse educator 
 
 
 
Social worker 
 
 
 
Technical  
(e.g., pacemaker company) 
 
 
 

 
Version <4.0> 
 
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3 
Other:          
 
 
 
 
3. Within the past 3 months, have you been visited in your home for heart failure education, attended a 
class, or a support/informational group?                       ❑Yes 
    
 
❑No  
 
3a. If yes, how long was each educational session and who participated in the education process with you. 
 
Purpose 
Length of 
Session 
How many 
times 
Who participated 
with (spouse/child/ 
sibling/other) 
Visited at home 
 
 
 
 
Attended a class 
 
 
 
 
Heart failure support 
group 
 
 
 
 
Other:          
 
 
 
 
 
4. Within the past 3 months, have you or other family members attended mental health counseling sessions 
for support?  
 
 
 
 
❑Yes     
 
❑No  
 
4a. If yes, how long was each counseling session and who participated in the process with you. 
 
Purpose 
Length of 
Session 
Who participated with 
(spouse/child/sibling/other) 
Session 1 
 
 
 
Session 2 
 
 
 
Session 3 
 
 
 
Session 4 
 
 
 
 

 
Version <4.0> 
 
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4 
5. Approximately how much did you spend for purchase or rental of health care–related 
equipment/medications for your health care over the past 3 months? 
 
Item related to heart failure 
Where purchased 
(mail order, pharmacy, or clinics) 
Cost that your insurance 
did not cover 
Medication  
 
 
Scale for weighing self 
 
 
Oxygen 
 
 
Heart failure device 
 
 
Batteries for device  
 
 
Alcohol wipes 
 
 
Dressing tape 
 
 
Item related to other conditions 
Where purchased 
(mail order, pharmacy, or clinics) 
Cost that your insurance 
did not cover 
Other medication  
 
 
Blood glucose meter 
 
 
Test strips 
 
 
Lancets 
 
 
Insulin (include all types) 
 
 
Insulin pen 
 
 
Insulin pump reservoirs and 
cartridges 
 
 
Insulin pump infusion sets 
 
 
Batteries for pump / meter 
 
 
Infusion set inserter 
 
 
Continuous glucose monitor 
 
 
Continuous glucose monitor sensor 
 
 
Ketosticks 
 
 
Supplies / food to treat 
hypoglycemia 
 
 
Pump accessories 
 
 
Medic alert bracelet or necklace 
 
 
Other supplies:           
 
 
 

 
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5 
 
Item related to mobility 
Where purchased 
(mail order, pharmacy, or clinics) 
Cost that your insurance 
did not cover 
Wheelchair 
 
 
Scooter 
 
 
Walker 
 
 
Cane 
 
 
Hospital bed 
 
 
Ramp 
 
 
Shower chair 
 
 
commode 
 
 
Other:          
 
 
 
 
 
6. Do you receive your health insurance from an employer?  
❑Yes        ❑No 
 
6a. What is your annual health insurance premium cost? $___________ 
 
6b. What is your annual health insurance deductible? $___________ 
 
 
 
The following questions ask about the effect of your health problems on your ability to work and perform 
regular activities during past 3 months. Please fill in the blanks or circle a number, as indicated. 
 
7. During the past 3 months, how much time (minutes) each week did you spend taking your medications, 
following your diet (making choices and eating), and weighing yourself?  ___________minutes 
 
8. During the past 3 months, how much time was spent taking care of technical issues (such as caring for heart 
related equipment)? ___________minutes 
 
 
 
9. Are you currently employed (working for pay)? 
  
 
❑Yes        ❑No   
❑Retired 
    ► If you answered ‘No’ or ‘Retired’, skip Questions 10 ~ 13 and go to Question 14.  

 
Version <4.0> 
 
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6 
 
14. During the past 3 months, how much did your health problems affect your ability to do your regular daily 
activities, other than work at a job? 
(By regular activities, we mean the usual activities you do, such as work around the house, shopping, child 
care, exercising, studying, and so forth. Think about times you were limited in the amount or kinds of 
activities you could do and times you accomplished less than you would like. If your health problems 
affected your activities only a little, choose a low number. Choose a high number if health problems 
affected your activities a great deal.) 
Consider only how much your heart failure affected your ability to do your regular daily activities, other than 
work at a job. Circle a number. 
 
Health problems had  
no effect on my daily 
activities 
 
 
 
 
 
Health problems 
completely prevented 
me from doing my daily 
activities 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
10. During the past 3 months, have you been absent from work because of illness?  
❑Yes        ❑No 
 
      10a. If yes, how many days? ___________, partial days: ___________ 
 
11. During the past 3 months, how many hours did you actually work?  ______  hours  
 
12. Does your workplace employ a nurse?   
 
❑Yes        ❑No 
 
12a. If yes, during the past 3 months, how much time (minutes) did you spend in the nurse’s office 
during the day? ___________minutes 
 
12b. How many days per week? ___________days 
 
13. During the past 3 months, how much did your health problems affect your productivity while you 
were working?   
(Think about days you were limited in the amount or kind of work you could do, days you 
accomplished less than you would like, or days you could not do your work as carefully as usual. If 
your health problems affected your work only a little, choose a low number. Choose a high number 
if health problems affected your work a great deal.) 
Consider only how much your heart failure affected productivity while you were working. Circle a 
number. 
 
Health problems had  
no effect on my work 
 
 
 
 
 
Health problems 
completely prevented 
me from working 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 

 
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18  
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