Clinical trial NCT05346653
Conditions: Acute Decompensated Heart Failure
Keywords: SGLT2i
Sponsor: University of Chicago
Start date: 2023-05-22; Completion date: 2023-05-23
Enrollment: 1 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The main purpose of this study is to observe hemodynamic effects of initiating sodium-glucose co-transporter 2 inhibitors (SGLT2i) in patients admitted to the intensive care unit (ICU) with acute decompensated heart failure.

Detailed description:
The exact mechanism of cardiovascular benefit from SGLT2i continues to be the source of further research. The investigators hypothesize that heart failure patients with acute decompensated heart failure will similarly benefit from the SGLT2i-associated natriuresis and diuresis. This mechanism should improve invasive hemodynamics during an inpatient ICU stay.

This is a prospective, randomized controlled study to assess cardiac benefit of SGLT2i in 40 consecutive patients admitted to University of Chicago Cardiac Intensive Care Unit (CCU) Advanced Heart Failure Service. Subjects will be randomized 1:1 to one of two routine care arms: treatment with an SGLT2i \[dapagliflozin 10 mg daily\] or no SGLT2i. After randomization, your SGLT2i and heart failure care will be managed according to routine care, and the investigators will collect the subject's medical data. The patient's treating physician will be able to override randomization assignment if they determine that the assignment is not in the patient's best interest.

Arms: arm 1: Participants will be treated with a SGLT2i during their ICU stay. The SGLT2i and heart failure care will be managed according to routine care, and data will be collected from the participant's medical record. arm 2: Participants will not be treated with a SGLT2i during their ICU stay. Heart failure care will be managed according to routine care, and data will be collected from the participant's medical record.
Interventions: intervention 1: SGLT2i intervention 2: No SGLT2i
Intervention descriptions: intervention 1: dapagliflozin (10 mg daily) intervention 2: No SGLT2i

Protocol documents:
Prot_SAP_000.pdf: 
Protocol Cover Page 
 
Official Title: The Hemodynamic Effects of Sodium-Glucose Co-Transporter 2 Inhibitors in 
Acute Decompensated Heart Failure 
NCT Number: NCT05346653 
Document Date: April 11, 2022 


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Protocol Title 
 
The Hemodynamic Effects of Sodium-Glucose Co-Transporter 2 Inhibitors in Acute 
Decompensated Heart Failure  
 
Principal Investigator 
Jonathan Grinstein, MD 
Department of Medicine, Section of Cardiology 
(773) 702-9396 
 
Objective:  
 
The main purpose of this study is to observe hemodynamic effects of initiating sodium-glucose 
co-transporter 2 inhibitors (SGLT2i) in patients admitted to the intensive care unit with acute 
decompensated heart failure. 
 
Study Purpose and Rationale: 
 
In 2008, the U.S. Food and Drug Administration (FDA) mandated new diabetes medications be 
tested for cardiovascular safety following the increase in heart failure hospitalizations seen with 
rosiglitazone in the RECORD trial (1). SGLT2i recently came onto the market, and accordingly 
multiple trials have assessed the cardiovascular safety of SGLT2i. These medications inhibit the 
sodium-glucose co-transporter 2 in the proximal tubule of the glomerulus, leading to reduced 
absorption, and increased excretion, of sodium and glucose (2). Not only were these medications 
found to be safe, but they have shown benefit in regards to cardiovascular outcomes.  
First, the EMPA-REG OUTCOME trial reported a significant reduction in the primary 
composite outcome of myocardial infarction, stroke, and cardiovascular death, as well as a 35% 
reduction in heart failure (HF) hospitalization in patients randomized to empagliflozin, versus 
placebo, with established atherosclerotic cardiovascular disease (ASCVD) (3). The CANVAS 
trial then showed similar results with canagliflozin in a mixed cohort of patients with established, 
or risk factors for, ASCVD (4). The DECLARE-TIMI-58 trial showed reduced cardiovascular 
death or HF hospitalization in patients randomized to dapagliflozin versus placebo. Interestingly, 
this trial had a majority of enrolled patients with only risk factors for ASCVD, without 
established disease. Additionally, the reduction in HF hospitalization was seen in both patients 
with and without HF at baseline, of which only 10% of enrolled patients carried the diagnosis 
(5).The DAPA-HF trial demonstrated significantly less major adverse cardiac events in heart 
failure with reduced ejection fraction patients, regardless of underlying diabetes status (6). Also, 
in the EMPEROR-REDUCED trial, empagliflozin reduced the composite end point of heart 
failure hospitalization or cardiovascular death (7). Lastly, in the SOLOIST-WHF trial, 
sotagliflozin was shown to reduce the total number of deaths from cardiovascular causes and 
hospitalization and urgent visits for heart failure compared to placebo when initiated during a 
heart failure hospitalization, or within three days of discharge (21).  Currently, dapagliflozin is 
FDA approved for use in patients with heart failure with reduced ejection fraction (HFrEF), 
regardless of diabetes status. 


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The proposed mechanism of reduction in heart failure hospitalization with SGLT2i is multi-
factorial, with the most significant reason thought to be due be reduced plasma volume and 
neurohormonal activation via its natriuretic and osmotic diuretic effects (8). Additionally, animal 
models have suggested favorable effects on the sympathetic nervous system and sodium-
hydrogen exchanger leading to reduced cardiac injury, hypertrophy, fibrosis, remodeling, and 
systolic dysfunction (9,10). Furthermore, increased ATP production, improved systolic function, 
and reduced cardiac work in non-diabetic mice with heart failure treated with empagliflozin, 
versus placebo, has been reported (11). In the updated 2021 Expert Consensus Decision Pathway 
for management of HFrEF, SGLT2i are recommended in patients on beta blockade and 
ARNI/ACE/ARB with EF ≤40%, NYHA Class II-IV HF, regardless of a diagnosis of diabetes 
(12).  
Multiple trials, including DAPA-HF and EMPEROR-Reduced, have shown that SGLT2i have 
been beneficial in reducing risk of cardiovascular death or hospitalization for patients with 
HFrEF, but these studies were not conducted in hospitalized acutely decompensated patients 
requiring ICU admission and continuous hemodynamic monitoring. Similarly, SOLOIST-WHF 
demonstrated a reduction in the same end points, where an SGLT2i was initiated within three 
days after a hospitalization for a heart failure exacerbation. Therefore, SGLT2i initiation was not 
conducted in an acutely decompensated clinical setting. While SGLT2i are FDA approved for 
use in HFrEF population, there are limited data specifically addressing the role of SGLT2i in the 
acute setting in patients with acute decompensated heart failure, and even less data related to its 
use in the patients requiring ICU-level care. Given the limited data, the decision whether or not 
to use SGLT2i in this population is currently based on the individual physician’s discretion. The 
exact mechanism of cardiovascular benefit continues to be the source of further research. We 
hypothesize that heart failure patients with acute decompensated heart failure will similarly 
benefit from the SGLT2i-associated natriuresis and diuresis. This mechanism should improve 
invasive hemodynamics during an inpatient ICU stay. 
Study Design, Study Procedures, and Statistical Procedures 
This study is designed as a single center, prospective, randomized controlled study to assess 
cardiac benefit of SGLT2i in 40 consecutive patients (20 treatment, 20 control) admitted to 
University of Chicago Cardiac Intensive Care Unit (CCU) Advanced Heart Failure Service. 
Patients will be randomized to one of two routine care arms: treatment with an SGLT2i 
(dapagliflozin 10 mg daily) or no SGLT2i. Assuming a power of 80% and alpha of 0.05, 16 
patients are needed in each arm of the study to detect a 5 mmHg change in pulmonary capillary 
wedge pressure (PCWP), and 18 patients are needed in each arm of the study to detect a 0.75 
L/min/m2 change in Fick cardiac index (CI). 
Patients ≥ 18 years old, with heart failure with reduced ejection fraction (HFrEF), defined as left 
ventricular ejection fraction (LVEF) < 40%, who are admitted to the CCU for acute 
decompensated heart failure and determined to need pulmonary artery catheter in place for 
continuous hemodynamic monitoring following right heart catherization, will be included in this 
study. Patients listed for cardiac transplantation or on mechanical support will be excluded. Due 
to the inability to consent patients following sedation given during the right heart catheterization, 


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patients determined to have a high likelihood of needing CCU admission, based on individual 
clinical presentation, will be approached for recruitment and asked for informed, written consent. 
However, patients will only be enrolled if it is determined independently to admit the patient to 
the CCU with the pulmonary artery catheter in place. If determined to need CCU care with 
continuous pulmonary artery catheter monitoring, patients will then be randomized, in a 1:1 
fashion using the random number generation function in Microsoft Excel, to either treatment 
with an SGLT2i (dapagliflozin 10mg once daily) or no SGLT2i. Therefore, we anticipate 
recruiting and consenting more than 40 patients, but we will only randomize and treat patients 
that fulfill all inclusion criteria. Patients consented but not meeting randomization criteria will 
not have any data collected or change to their management. 
The patient’s treating physician will be able to override randomization assignment if the 
physician determines that the assignment is not in the patient’s best interest. These patients 
would be kept on study and their data would be used for observational research within this study. 
Data points to be collected: Leveled invasive hemodynamics measured via pulmonary artery 
catheter at end expiration, standing weights, intake and outputs, blood glucose from basic 
metabolic panels (BMP) taken at those time points, HbA1C (if not within 3 months), blood 
pressure (cuff pressure), vasoactive doses, and renal function (measured by serum creatinine and 
estimated GFR) will be captured at multiple time points during CCU admission, as described 
below. All data points collected for use in this study are being measured as part of the patient’s 
routine care. 
(1) Cardiac catherization lab prior to CCU arrival: Initial baseline hemodynamics 
obtained in the cardiac catherization lab prior to CCU arrival will be collected.  
a) Cardiac index (L/min/m2) by Indirect Fick Method 
b) Right atrial pressure (RAP) (mmHg) 
c) Pulmonary artery systolic pressure (PASP) (mmHg) 
d) Mean pulmonary artery pressure (mPA) (mmHg) 
e) Pulmonary artery diastolic pressure (PADP) (mmHg) 
f) Pulmonary capillary wedge pressure (PCWP) (mmHg) 
g) Pulmonary artery pulsatility index (PAPI) 
h) Right ventricular stroke work index (RVSWI) (mmHg L-1 m-2) 
i) Systemic vascular resistance (SVR) (dynes/sec/cm5) 
j) Pulmonary vascular resistance (PVR) (dynes/sec/cm5) 
k) Systolic, diastolic, and mean blood pressure (SBP/DBP/MAP) (mmHg) 
l) Aortic pulsatility index (API) 
(2) Hour 0 – Leveled hemodynamics, repeated within two hours of arrival to CCU bed from 
cardiac catherization lab prior to SGLT2i administration/equivalent if randomized to no 
SGLT2i arm, will be collected. All baseline data points to be collected at this time. 
a. Cardiac index (L/min/m2) 
b. RAP (mmHg) 
c. PASP (mmHg) 


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d. mPA (mmHg) 
e. PADP (mmHg) 
f. PCWP (mmHg) 
g. PAPi  
h. RVSWI (mmHg L-1 m-2) 
i. SVR (dynes/sec/cm5) 
j. PVR (dynes/sec/cm5) 
k. SBP/DBP/MAP 
l. API 
m. Standing weight 
n. Urine output 
o. Blood glucose taken from BMP 
p. HbA1c 
q. Current Vasoactive doses  
r. Renal function (serum Creatinine, serum eGFR) 
s. Total diuretic dose 
(3) Hour 1 – Following repeat hemodynamics in CCU bed, patients will be given SGLT2i if 
randomized to SGLT2i arm, or not given SGLT2i if randomized to no SGLT2i arm. 
(4) Hour 3  
a. Cardiac index (L/min/m2) 
b. RAP (mmHg) 
c. PASP (mmHg) 
d. mPA (mmHg) 
e. PADP (mmHg) 
f. PCWP (mmHg) 
g. PAPi  
h. RVSWI (mmHg L-1 m-2) 
i. SVR (dynes/sec/cm5) 
j. PVR (dynes/sec/cm5) 
k. SBP/DBP/MAP 
l. API 
m. Standing weight 
n. Urine output 
o. Blood glucose taken from BMP 
p. HbA1c 
q. Current Vasoactive doses  
r. Renal function (serum Creatinine, serum eGFR) 
s. Total diuretic dose 
(5) Hour 27 - 2 hours after 2nd dose of SGLT2i, which will be administered 24 hours after 
first dose, or equivalent time period after which the dose would have been given for the No-
SGLT2i arm. 


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a. Cardiac index (L/min/m2) 
b. RAP (mmHg) 
c. PASP (mmHg) 
d. mPA (mmHg) 
e. PADP (mmHg) 
f. PCWP (mmHg) 
g. PAPi  
h. RVSWI (mmHg L-1 m-2) 
i. SVR (dynes/sec/cm5) 
j. PVR (dynes/sec/cm5) 
k. SBP/DBP/MAP 
l. API 
m. Standing weight 
n. Urine output 
o. Blood glucose taken from BMP 
p. HbA1c 
q. Current Vasoactive doses  
r. Renal function (serum Creatinine, serum eGFR) 
s. Total diuretic dose 
(6) Hour 51 & Hour 75 - if vasoactives are still required and pulmonary artery catheter 
is still being used for routine clinical care, we will continue SGLT2i for up to 4 doses, and 
the additional invasive hemodynamics repeated two hours after each dose will be collected. 
a. Cardiac index (L/min/m2) 
b. RAP (mmHg) 
c. PASP (mmHg) 
d. mPA (mmHg) 
e. PADP (mmHg) 
f. PCWP (mmHg) 
g. PAPi  
h. RVSWI (mmHg L-1 m-2) 
i. SVR (dynes/sec/cm5) 
j. PVR (dynes/sec/cm5) 
k. SBP/DBP/MAP 
l. API 
m. Standing weight 
n. Urine output 
o. Blood glucose taken from BMP 
p. HbA1c 
q. Current Vasoactive doses  
r. Renal function (serum Creatinine, serum eGFR) 
s. Total diuretic dose 
Leveled invasive hemodynamic measurements, standing weights, intake and outputs, blood 
glucose, blood pressure, vasoactive doses, and renal function will stop being collected for the 


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study after the fourth dose of SGLT2i, or equivalent timing for those randomized to the No-
SGLT2i arm. 
 
The leveled hemodynamic measurements measured via a pulmonary artery catheter at end 
expiration will be collected. A picture will be taken and shown to an Advanced HF attending not 
involved with the patient’s current care and blinded to treatment for interpretation.  
The patient’s participation in the study will end after completion of 4 doses of the SGLT2i or 
sooner if patient is transferred out of the CCU and continuous hemodynamic monitoring is 
discontinued, or if patient develops any of the safety end points as listed below. The physician 
will discuss the ongoing treatment plan with the patient at this point. 
Outcomes 
Primary outcome: Change in Indirect Fick cardiac index and change in PCWP  
Secondary outcomes: changes in pulmonary artery pulsatility index (PAPi), Right atrial pressure 
(RAP), pulmonary artery systolic pressure (PASP), mean pulmonary artery pressure (mPA), 
pulmonary artery diastolic pressure (PADP), right ventricular stroke work index (RVSWI), 
systemic vascular resistance (SVR), pulmonary vascular resistance (PVR), mean arterial pressure 
(MAP), renal function, 24 hour urine output, changes in weight, changes in vasoactive dose, and 
blood glucose levels 
Safety End Points 
1. Need for initiation of second vasoactive medication and/or MAP < 60 
2. Development of acute kidney injury, based on eGFR value < 30ml/min/1.73m2 
3. Adverse events reflecting urinary tract infection, genital infection, bone fracture, and 
diabetic ketoacidosis 
Study Drugs  
There are no new study drugs being used in this study. Per the FDA “SGLT2 inhibitors are a 
class of prescription medicines that are FDA-approved for use with diet and exercise to lower 
blood sugar levels in adults with type 2 diabetes. Medicines in the SGLT2 inhibitor class include 
canagliflozin, dapagliflozin, and empagliflozin” (18). In May 2020, the FDA approved 
dapagliflozin for use in HFrEF, regardless of diabetes status (19).  
Study Subjects 
The study will include patients at UCMC who are admitted to the CCU by the advanced heart 
failure service after right heart catherization for acute decompensated heart failure requiring 
vasoactive support. 
Inclusion Criteria 


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1. Age > 18 years old 
2. Reduced ejection fraction (HFrEF) of 40 or less 
3. Estimated glomerular filtration rate (eGFR) > 30ml/min/1.73m2 
4. Admitted to CCU by advanced heart failure service for decompensated heart failure 
requiring continuous hemodynamic monitoring with a pulmonary artery catheter 
Exclusion Criteria 
1. Diagnosis of type 1 DM 
2. eGFR < 30ml/min/1.73m2 
3. age < 18 years old 
4. Jehovah’s witnesses 
5. Diagnosis of group 1 pulmonary arterial hypertension 
6. Insulin requirement above standard low dose sliding scale 
7. Patients with a history of DKA 
8. Allergies to SGLT2i medications 
9. History of intolerance to SGLT2i medications 
10. Patients listed for cardiac transplantation or on mechanical support 
11. Pregnant or breastfeeding  
Recruitment 
Patients undergoing a right heart catheterization, either as outpatient or inpatient, who are 
determined to have a high likelihood of needing CCU admission for acute decompensated heart 
failure requiring continuous invasive hemodynamic monitoring with a pulmonary artery catheter, 
will be recruited by members of the Advanced Heart Failure team. Patients will be approached 
before sedation is given for the right heart catheterization procedure.  
Informed Consent Process 
The consent process will take place during a routine visit or inpatient hospital stay. Patients will 
be given an informed consent and allowed as much time as needed to read all components and be 
provided time to formulate questions. If questions arise, the PI or a member of the research team 
will provide answers to the patient regarding participation in the research study. Family members 
or caretakers will also be encouraged to participate in the informed consent process if applicable. 
Ample time will be given for the informed consent process. After a complete explanation of the 
study, the informed consent document will be reviewed. Subjects will be asked to verbalize their 
understanding of the study and encouraged to ask questions. Family members or caretakers will 
also be encouraged to participate in the informed consent process if applicable. 
Confidentiality of Study Data and Privacy Protections 
Data will be abstracted into an electronic database. The database will be within the UCMC 
Department of Medicine, Section of Cardiology. The data will be password protected and 
covered by all of the firewalls and security features of the Department of Medicine. The data will 


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also be housed on a password protected encrypted laptop using University of Chicago standards 
per CBIS. 
Once collected, an individual’s data will not be available to anyone other than the investigators 
and study personnel involved in this project. The data will be abstracted and entered into an 
electronic database by a member of the research team.  The database will be within the 
Department of Medicine, Section of Cardiology. The data will be password protected and 
covered by all of the firewalls and security features of the Department of Medicine. Name, 
address, email address, phone number and medical record number will be stored separately from 
the database. In the database, a code will be recorded with the data instead. Only the study staff 
will be able to link the code to the subject’s name and other identifying information. The link to 
identifiers will be destroyed at the end of 6 years per HIPAA regulations. 
Potential Risks 
SGLT2i have been shown to have beneficial effects on renal function (5,20). However, due to its 
direct effect on the kidneys, SGLT2i are labeled for patients with eGFR > 20ml/min/1.73m2 or 
GFR > 30ml/min/1.73m2 depending on the medication. Due to this, we will exclude patients with 
eGFR < 30ml/min/1.73m2. Increased risk of genital mycotic infections (i.e. vaginitis and 
balanitis), urinary tract infections, pyelonephritis, urosepsis, and perineal necrotizing fasciitis 
have been reported, but only genital infections have been shown to be a significant risk in large 
randomized trials (3-5). Additionally, there has been a small increased risk of diabetic 
ketoacidosis associated with the use of SGLT2i, though this was predominantly in patients on 
insulin, who will not be included in this study (5). Lastly, canagliflozin was associated with an 
elevated risk of lower limb amputation and bone fractures compared to placebo in the CANVAS 
trial, but this was not seen with the CREEDANCE trial of canagliflozin, or in other SGLT2i 
randomized controlled trials, including the EMPA-REG OUTCOME, DECLARE-TIMI-58, 
DAPA-HF, EMPEROR-Reduced trials completed for empagliflozin and dapagliflozin (4). We 
will not be using canagliflozin in this study. 
The adverse reactions of dapagliflozin in order of incidence include female genital mycotic 
infections, nasopharyngitis, urinary tract infection, back pain, increased urination, male genital 
mycotic infections, nausea, influenza, dyslipidemia, constipation, dysuria, pain in extremity, 
increase in creatinine, increase in hematocrit, dyslipidemia, hypersensitivity reactions, urosepsis, 
necrotizing fasciitis of the perineum.  
Since patients are randomized to two routine care arms, we do not believe there is additional risk 
incurred by participating in this study. The treating physician will be notified of the 
randomization assignment and can override the assignment if they believe it to be in the best 
interest of the patient. While SGLT2 inhibitor therapy is approved for use in patients with 
HFrEF, there is not sufficient data guiding its use in the ICU-setting in patients with acute 
decompensated heart failure. If benefit is shown in the SGLT2i population, the arm without 
SGLT2i would lose the hypothesized benefit of renal and cardiovascular benefits during the 
CCU stay.  
 


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Data and Safety Monitoring 
Data safety measures will be maintained as above. Appropriate CBIS and risk management 
personnel will be contacted immediately if any data loss is suspected. All patients in this study 
are closely monitored throughout the duration of activity in this study as, by nature, they are in 
the CCU. Any study-related adverse events will be reported to the IRB according to the IRB’s 
reporting requirements. Adverse events related to the SGLT2i will be reported to the 
manufacturer or directly to the FDA as would normally occur for safety reporting of routine 
medications.  
40 subjects in this initial pilot study are followed for less than 4 days. We believe that this is the 
minimum required to clarify potential benefit of SGLT2 inhibitor therapy in the acute setting in 
patients with acute decompensated heart failure. We do not anticipate adequate data prior to 
study completion evidencing benefit that would justify study stoppage or redesign. 
Potential Benefits 
SGLT2i data indicates improvement in cardiovascular outcomes, including cardiovascular death 
and heart failure hospitalization in patients with and without known heart failure (3-7). The 
proposed mechanisms of action of SGLT2i leading to these improved cardiovascular outcomes, 
specifically increased natriuresis and diuresis and reduced cardiac work and remodeling should 
have beneficial effects on patients with acute decompensated heart failure (9-11,13-17). 
Recently, it has been shown that SGLT2i decreased heart failure exacerbations and 
cardiovascular mortality regardless of a diagnosis of diabetes (6,7). To this end, the 2021 Heart 
Failure Treatment guidelines have updated its recommendations to include SGLT2i as standard 
of care. Therefore, it is hypothesized that the benefit of SGLT2i seen in HFrEF patients will also 
be effective in the acute setting in patients with acute decompensated heart failure.  
Alternatives 
Participation is voluntary, and the alternative is not to participate in this study. Outside of the 
study, the decision whether or not the patient receives an SGLT2i would be based on the treating 
physician’s discretion. 
Research at External Sites: 
All research will be conducted at University of Chicago Medical Center (UCMC). This is not a 
multicenter study; thus, University of Chicago will be the only institution involved with the 
research.  
References: 
1. 
Home PD, Pocock SJ, Beck-Nielsen H et al. Rosiglitazone evaluated for cardiovascular 
outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a 
multicentre, randomised, open-label trial. Lancet 2009;373:2125-35. 


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2. 
Zelniker TA, Braunwald E. Cardiac and Renal Effects of Sodium-Glucose Co-
Transporter 2 Inhibitors in Diabetes: JACC State-of-the-Art Review. J Am Coll Cardiol 
2018;72:1845-1855. 
3. 
Zinman B, Wanner C, Lachin JM et al. Empagliflozin, Cardiovascular Outcomes, and 
Mortality in Type 2 Diabetes. N Engl J Med 2015;373:2117-28. 
4. 
Neal B, Perkovic V, Mahaffey KW et al. Canagliflozin and Cardiovascular and Renal 
Events in Type 2 Diabetes. N Engl J Med 2017;377:644-657. 
5. 
Wiviott SD, Raz I, Bonaca MP et al. Dapagliflozin and Cardiovascular Outcomes in Type 
2 Diabetes. N Engl J Med 2019;380:347-357. 
6. 
McMurray JJV, Solomon SD, Inzucchi SE et al. Dapagliflozin in Patients with Heart 
Failure and Reduced Ejection Fraction. N Engl J Med 2019. 
7. 
Packer M, Anker SD, Butler J et al. Cardiovascular and Renal Outcomes with 
Empagliflozin in Heart Failure. N Engl J Med 2020;383:1413-1424. 
8. 
Crawford PA. Refueling the Failing Heart: A Case for Sodium-Glucose Cotransporter 2 
Inhibition in Cardiac Energy Homeostasis. JACC Basic Transl Sci 2018;3:588-590. 
9. 
Baartscheer A, Schumacher CA, Wust RC et al. Empagliflozin decreases myocardial 
cytoplasmic Na(+) through inhibition of the cardiac Na(+)/H(+) exchanger in rats and 
rabbits. Diabetologia 2017;60:568-573. 
10. 
Uthman L, Baartscheer A, Bleijlevens B et al. Class effects of SGLT2 inhibitors in 
mouse cardiomyocytes and hearts: inhibition of Na(+)/H(+) exchanger, lowering of 
cytosolic Na(+) and vasodilation. Diabetologia 2018;61:722-726. 
11. 
Byrne NJ, Parajuli N, Levasseur JL et al. Empagliflozin Prevents Worsening of Cardiac 
Function in an Experimental Model of Pressure Overload-Induced Heart Failure. JACC 
Basic Transl Sci 2017;2:347-354. 
12. 
Writing C, Maddox TM, Januzzi JL, Jr. et al. 2021 Update to the 2017 ACC Expert 
Consensus Decision Pathway for Optimization of Heart Failure Treatment: Answers to 
10 Pivotal Issues About Heart Failure With Reduced Ejection Fraction: A Report of the 
American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol 
2021;77:772-810. 
13. 
Borgi J, Tsiouris A, Hodari A, Cogan CM, Paone G, Morgan JA. Significance of 
postoperative acute renal failure after continuous-flow left ventricular assist device 
implantation. Ann Thorac Surg 2013;95:163-9. 
14. 
Sabashnikov A, Mohite PN, Zych B et al. Outcomes and predictors of early mortality 
after continuous-flow left ventricular assist device implantation as a bridge to 
transplantation. ASAIO J 2014;60:162-9. 
15. 
Romano MA, Cowger J, Aaronson KD, Pagani FD. Diagnosis and management of right-
sided heart failure in subjects supported with left ventricular assist devices. Curr Treat 
Options Cardiovasc Med 2010;12:420-30. 
16. 
Miyagawa S, Toda K, Nakamura T et al. Building a bridge to recovery: the 
pathophysiology of LVAD-induced reverse modeling in heart failure. Surg Today 
2016;46:149-54. 
17. 
Burkhoff D, Sayer G, Doshi D, Uriel N. Hemodynamics of Mechanical Circulatory 
Support. J Am Coll Cardiol 2015;66:2663-2674. 
18. 
Sodium-glucose Cotransporter-2 (SGLT2) Inhibitors. FDA, 2018. 
19. 
Administration USFaD. FDA approves new treatment for a type of heart failure. 2020. 


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20. 
Zelniker TA, Wiviott SD, Raz I et al. SGLT2 inhibitors for primary and secondary 
prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review 
and meta-analysis of cardiovascular outcome trials. Lancet 2019;393:31-39. 
21.       Bhatt D, Szarek M, Steg G,  et al. Sotagliflozin in Patients with Diabetes and Recent 
Worsening Heart Failure. N Engl J Med 2021; 384:117-128 

ICF_001.pdf: 
ICF Cover Page 
 
Official Title: The Hemodynamic Effects of Sodium-Glucose Co-Transporter 2 Inhibitors in 
Acute Decompensated Heart Failure 
NCT Number: NCT05346653 
Document Date: April 15, 2022 


IRB22-0346 | Version: 2022Apr15
Page 1 of 9
The UNIVERSITY OF CHICAGO
The Division of the Biological Sciences  The University of Chicago Medical Center
CONSENT/AUTHORIZATION FOR PARTICIPATION IN A RESEARCH PROTOCOL
Protocol Number: 
IRB22-0346
Name of Subject:  
Medical History Number:  _______________________________
STUDY TITLE: The Hemodynamic Effects of Sodium-Glucose Co-Transporter 2 Inhibitors in Acute 
Decompensated Heart Failure
Doctor Directing Research: Dr. Jonathan Grinstein  
Address: 5841 South Maryland Avenue
    MC 2016
    Chicago, Illinois 60637
Telephone Number: (773) 702-9396
KEY INFORMATION 
We are asking you to choose whether or not to volunteer for a research study about a Sodium-Glucose 
Co-Transporter 2 Inhibitor (SGLT2i) drug called dapagliflozin in people who have been admitted to the 
intensive care unit (ICU) after a right heart catheterization procedure. The purpose of this section is to 
give you key information to help you decide whether to participate. We have included detailed 
information after this section. Ask the research team questions. If you have questions later, the contact 
information for the research investigator in charge of the study is above. 
WHAT IS THE STUDY ABOUT AND HOW LONG WILL IT LAST? 
You are being asked to take part in this study because you have heart failure, you are scheduled for a 
right heart catheterization procedure as part of your routine care, and your doctor thinks you may need to 
be admitted to the ICU after the procedure. Heart failure occurs when the heart muscle does not pump 
blood as well as it should. A right heart catheterization procedure is a test done to see how well your 
heart is pumping. After a right heart catheterization procedure, some patients may need to be admitted to 
the ICU for more tests and treatment if the pressure in their heart or lungs is very high or if the heart is 
not pumping enough blood. During the ICU stay, doctors closely monitor the condition of their patients 
and may give them medications for their heart failure care and other related conditions. One example of 
a type of medication that may be given is a SGLT2i drug called dapagliflozin. 
The SGLT2i used in this study, dapagliflozin, is approved by the Food and Drug Administration to 
reduce the risk of hospitalization and death in patients with certain types of heart failure. This includes 
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patients with your type of heart failure; however, more information is needed to better understand how 
patients admitted to the ICU might benefit from SGLT2i. By doing this study, we hope to learn more 
about the possible benefits. 
If your treating physician does not admit you to the ICU after your right heart catheterization procedure, 
you will not be able to join this study. 
In this study, we will compare patients in the ICU who are given a SGLT2i to patients who are not given 
SGLT2i. Normally, the decision to give a SGLT2i or not is up to the individual doctor. Both scenarios 
are considered within routine care for ICU patients. If you join this study, the decision will be made by a 
computer program. You will be randomly assigned (like the flip of a coin) to one of the two study 
groups: 
1) SGLT2i 
2) No SGLT2i
You will have an equal chance of being in either group. This assignment process is called 
randomization. We will tell you and your doctor which study group you get assigned to. If your doctor 
believes that your group assignment is not the best treatment option for your medical condition, their 
treatment decision will override your group assignment, and you will be changed to the group your 
doctor thinks you should be in. 
If you are in the SGLT2i group, you will be given dapagliflozin during your ICU stay. For all subjects, 
after randomization, heart failure care and SGLT2i (if applicable) will be managed according to routine 
care. We will collect information from your medical records for this study. Your participation in this 
research will last about four days. 
WHAT ARE KEY REASONS YOU MIGHT CHOOSE TO VOLUNTEER FOR THIS STUDY?
Being in this study may not help you directly. We hope that your participation in the study will benefit 
other people in the future by helping us learn more about treatments for heart failure. For a complete 
description of benefits, refer to the Detailed Consent Section below.
WHAT ARE KEY REASONS YOU MIGHT CHOOSE NOT TO VOLUNTEER FOR THIS 
STUDY? 
You may choose not to participate in this study if you have concerns about the risks involved. The main 
risk of participation is loss of confidentiality. The research team will take care to protect your 
confidentiality throughout the study. 
If you are assigned to the SGLT2i study group, the most serious side effects associated with 
dapagliflozin include the following. You may be at risk for the same side effects if you are prescribed 
dapagliflozin outside of the study. 
•
Ketoacidosis (increased ketones in your blood or urine)
o
Ketoacidosis has happened in people with diabetes. Ketoacidosis is a serious 
condition, which needs to be treated in a hospital. Ketoacidosis may lead to death.
•
Necrotizing fasciitis of the perineum [a rare but serious bacterial infection that causes 
damage to the tissue under the skin (necrotizing fasciitis) in the area between and around the 
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anus and genitals (perineum)]
o
Necrotizing fasciitis of the perineum may lead to hospitalization, may require 
multiple surgeries, and may lead to death. 
o
Signs and symptoms may include fever, feeling very weak, tired or uncomfortable 
(malaise), and you develop any of the following symptoms in the area between and 
around your anus and genitals: pain or tenderness, swelling, redness of skin 
(erythema).
For a complete description of risks, refer to the Detailed Consent Section below.  
Instead of being in this study, you may choose not to participate. You do not need to participate in this 
study to receive treatment with a SGLT2i. Outside of the study, the decision whether or not you receive 
a SGLT2i or not would be up to your treating physician. For a complete description of alternate 
treatments, refer to the Detailed Consent Section below.
DO YOU HAVE TO TAKE PART IN THE STUDY? 
Taking part in this study is voluntary. If you decide to take part in the study, it should be because you 
really want to volunteer. You will not lose any services, benefits or rights you would normally have if 
you choose not to volunteer. 
You may choose not to participate at any time during the study. You will not lose any services, benefits, 
or rights you would normally have if you choose to leave the study. The University of 
Chicago/University of Chicago Medical Center will not condition (withhold or refuse) treating you on 
whether you sign this Authorization or revoke your authorization at a later time. If you do not sign this 
form, you will not receive the research-related intervention(s).
WHAT IF YOU HAVE QUESTIONS, SUGGESTIONS, OR CONCERNS? 
The person in charge of the study is Dr. Grinstein of the University of Chicago. If you have questions, 
suggestions, or concerns regarding this study, or if you want to withdraw from the study, his contact 
information is: (773) 702-9396. 
If you have a research-related injury, you should immediately contact Dr. Grinstein at (773) 702-9396. 
In case of emergency, call (773) 702-6800 and ask for pager # 4016.
For questions about your rights as a research subject, please contact the University of Chicago BSD IRB 
at 773-702-6505.
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DETAILED CONSENT
WHAT IS INVOLVED IN THE STUDY?
About 40 people will take part in this study at the University of Chicago.
If you agree to participate in this research study, you will be asked to sign this consent form. If you sign 
the consent form, but your treating physician does not admit you to the ICU after your right heart 
catheterization procedure, you will not be able to join this study. 
Randomization
Normally, the decision to give a SGLT2i or not is up to the individual doctor. Both scenarios are 
considered within routine care for ICU patients. If you join this study, the decision will be made by a 
computer program instead. If your treating physician decides to admit you to the ICU, you will be 
randomly assigned (like the flip of a coin) to one of the two study groups: 
1) SGLT2i 
2) No SGLT2i 
You will have an equal chance of being in either group. We will tell you and your doctor which study 
group you get assigned to. If your doctor believes that your group assignment is not the best treatment 
option for your medical condition, their treatment decision will override your group assignment, and you 
will be changed to the group your doctor thinks you should be in. If this happens, we will still collect 
your medical data as described below.
SGLT2i Group
If you are in this group, you will be given dapagliflozin during your ICU stay. You will be given 
dapagliflozin once a day for up to 4 days or until you are transferred out of the ICU. After 
randomization, your SGLT2i and heart failure care will be managed according to routine care, and we 
will collect your medical data for this study as described below. After you finish taking dapagliflozin for 
this study, your doctor will discuss your ongoing treatment plan with you.
No SGLT2i Group
If you are in this group, you will not be given dapagliflozin. After randomization, your heart failure care 
will be managed according to routine care. We will collect your medical data for this study as described 
below. 
Data Collection
We will collect the following information from your medical records about your right heart 
catheterization procedure and ICU stay:

Information about your health status

Information about your medications 

Right heart catheterization results 

Laboratory test results 

Hemodynamic measurements (measurements of the pressures in your heart and lungs)
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Other Information
In the future, identifiers associated with your data could be removed from the data. The de-identified 
data could then be used for future research by our research team or other researchers without notifying 
you or asking your permission for this use. 
The results from this study will not be shared with you. 
Dr. Grinstein may decide to take you off of the study without your consent if: 
•
You are unable to meet the requirements of the study or your medical condition changes;
•
New information becomes available that indicates that participation in this study is not in your 
best interest; or
•
If the study is stopped.
WHAT ARE THE RISKS OF THE STUDY?
During your participation in this study, you are at risk for the following. You should discuss these with 
the study doctor. There may also be other risks that we cannot predict.
Loss of Confidentiality
Any time information is collected about you there is a potential risk for loss of confidentiality. However, 
the researchers will make every effort to keep your information confidential. Please see the “What about 
Confidentiality?” section below for more information.
Risks of dapagliflozin (SGLT2i group only)
There are known side effects associated with taking the SGLT2i drug dapagliflozin. The following side 
effects are taken from the FDA Medication Guide. You may be at risk for the same side effects if you 
are prescribed dapagliflozin outside of the study. 
The most common side effects of include: 
•
Vaginal yeast infections and yeast infections of the penis 
•
Stuffy or runny nose and sore throat 
•
Changes in urination, including urgent need to urinate more often, in larger amounts, or at night
Serious side effects include: 
•
Dehydration (a dangerous loss of body fluid)
o
Dehydration may cause you to feel dizzy, faint, light-headed, or weak, especially when 
you stand up (orthostatic hypotension).
o
There have been reports of sudden kidney injury in people with Type 2 diabetes who are 
taking this medication.
•
Vaginal yeast infection
o
Symptoms include vaginal odor, white or yellowish vaginal discharge (discharge may be 
lumpy or look like cottage cheese), vaginal itching.
•
Yeast infection of the penis (balanitis)
o
Certain men who are not circumcised may have swelling of the penis that makes it 
difficult to pull back the skin around the tip of the penis. Other symptoms of yeast 
infection of the penis include redness, itching, or swelling of the penis; rash of the penis; 
foul smelling discharge from the penis; pain in the skin around the penis.
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•
Ketoacidosis (increased ketones in your blood or urine)
o
Ketoacidosis has happened in people with diabetes. Ketoacidosis is a serious condition, 
which needs to be treated in a hospital. Ketoacidosis may lead to death.
o
Symptoms may include nausea, tiredness, vomiting, trouble breathing. stomach area 
(abdominal) pain.
•
Serious urinary tract infections
o
Signs or symptoms of a urinary tract infection include a burning feeling when passing 
urine, a need to urinate often, the need to urinate right away, pain in the lower part of 
your stomach (pelvis), or blood in the urine. Sometimes people also may have a fever, 
back pain, nausea or vomiting.
o
Serious urinary tract infections that may lead to hospitalization have happened in people 
who are taking this medication.
•
Low blood sugar (hypoglycemia)
o
If you take this medication with another medicine that can cause low blood sugar, your 
risk of getting low blood sugar is higher.
o
Signs and symptoms may include headache, irritability, confusion, dizziness, drowsiness, 
hunger, shaking or feeling jittery, sweating, weakness, and fast heartbeat. 
•
Necrotizing fasciitis of the perineum [a rare but serious bacterial infection that causes damage to 
the tissue under the skin (necrotizing fasciitis) in the area between and around the anus and 
genitals (perineum)]
o
Necrotizing fasciitis of the perineum may lead to hospitalization, may require multiple 
surgeries, and may lead to death. 
o
Signs and symptoms may include fever, feeling very weak, tired or uncomfortable 
(malaise), and you develop any of the following symptoms in the area between and 
around your anus and genitals: pain or tenderness, swelling, redness of skin (erythema).
Unknown Risks
There may be other risks that could arise which are not reasonably foreseeable. If new information 
becomes available which could influence your willingness to continue, this new information will be 
discussed with you.
ARE THERE ANY BENEFITS TO TAKING PART IN THE STUDY?
Being in this study may not help you directly. We hope that your participation in the study will benefit 
other people in the future by helping us learn more about treatments for heart failure.
WHAT OTHER OPTIONS ARE THERE?
Instead of being in this study, you may choose not to participate. You do not need to participate in this 
study to receive treatment with a SGLT2i. Outside of the study, the decision whether or not you receive 
a SGLT2i or not would be up to your treating physician.
WHAT ARE THE COSTS?
There will be no costs to you or your insurance company resulting from your participation in this 
research study. However, you or your insurance company will be responsible for costs related to your 
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usual medical care, such as your overnight hospital stays, because these are happening as part of your 
routine care. If you are in the SGLT2i group, you or your insurance company will also be responsible for 
costs related to your SGLT2i treatment and treatment for the known side effects you may experience, 
because these are happening as part of your routine care.
WHAT HAPPENS IF I HAVE AN INJURY?
If you suffer an unanticipated injury as a direct result of this research and require emergency medical 
treatment, the University of Chicago Medical Center will provide such treatment at the University of 
Chicago Medical Center at no cost to you. You must notify Dr. Grinstein as promptly as possible after 
your injury in order to receive this care. An injury is “unanticipated” if it is not one of the known effects 
of a study drug, medical device or procedure, and is not the result of your disease or condition. The costs 
of any non-emergency care for such an injury will be billed to you or your insurance in the ordinary 
manner. If you think that you have suffered a research related injury, you must let Dr. Grinstein know 
right away.
WILL I BE PAID FOR MY PARTICIPATION?
You will not be paid to participate in this study.
WHAT ABOUT CONFIDENTIALITY?
There is a risk of potential loss of confidentiality. To minimize this risk, study records that identify you 
will be kept confidential. Data will be stored in a locked drawer in a locked office and/or entered on a 
password-protected, HIPAA-compliant computer. Only the research team will have access to the data. 
During this study, Dr. Grinstein and his research team will collect protected health information (PHI) 
about you for the purposes of this research. The research team includes the individuals listed on this 
consent form and other personnel involved in this study at the University of Chicago. Protected Health 
Information (PHI) consists of any health information that is collected about you, which could include 
your medical history and new information collected as a result of this study. Most of this information 
will come from your medical record. The information to be used on this study includes your name, 
medical record number, and dates (including date of birth and dates related to your heart failure care). 
This information will be used to collect data for the study, and some of it will be collected as data for 
study analysis. 
Your records may be reviewed by federal agencies whose responsibility is to protect human subjects in 
research including the Office of Human Research Protections (OHRP). Representatives of the 
University of Chicago, including the Institutional Review Board (a committee that oversees the 
research) and the Office of Clinical Research may also view the records of the research. If your research 
record is reviewed by any of these groups, they may also need to review your entire medical record. 
Once information is shared outside the University of Chicago, please note that your identifiable health 
information may be shared with someone else. The same laws that the University of Chicago must obey 
may not protect your health information.
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During your participation in this study, you will have access to your medical record. Dr. Grinstein is not 
required to release to you research information that is not part of your medical record.
This consent form will be kept by the research team for at least six years. The study results will be kept 
in your research record and be used by the research team until completion of this study. At the time of 
study completion, either the research information not already in your medical record will be destroyed or 
information identifying you will be removed from study results. 
Data from this study may be used in medical publications or presentations. Your name and any other 
identifying information will be removed before this data is used. If we wish to use identifying 
information in publications, we will ask for your approval at that time. We may also share de-identified 
data with collaborators or others for research purposes.
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. 
Law. This Web site will not include information that can identify you. At most, the Web site will 
include a summary of the results. You can search this Web site at any time.
WHAT ARE MY RIGHTS AS A PARTICIPANT?
If you choose to no longer be in the study and you do not want any of your future health information to 
be used, you must inform Dr. Grinstein in writing at the address on the first page. Dr. Grinstein may still 
use your information that was collected prior to your written notice. 
We will tell you about significant new information that may affect your willingness to stay in this study. 
You will be given a signed copy of this document. Your authorization to use and disclose your health 
information does not have an expiration date.
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CONSENT
SUBJECT
The research project and the procedures associated with it have been explained to me. The experimental 
procedures have been identified and no guarantee has been given about the possible results. I will 
receive a signed copy of this consent form for my records.
I agree to participate in this study. My participation is voluntary and I do not have to sign this form if I 
do not want to be part of this research study.
Signature of Subject:  
         
      
    
Date:  
Time:  
   AM/PM (Circle)
PERSON OBTAINING CONSENT
I have explained to 
 the nature and purpose of the 
study and the risks involved. I have answered and will answer all questions to the best of my ability. I 
will give a signed copy of the consent form to the subject.
Signature of Person Obtaining Consent:  
         
  
Date:  
Time:  
   AM/PM (Circle)
INVESTIGATOR/PHYSICIAN:
Signature of Investigator/Physician:  
Date:  
Time:  
   AM/PM (Circle)
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