sponsor innovation webinar...sponsor innovation webinar nora o’buck, rn-bsn, ccrn program manager,...

Sponsor Innovation Webinar

Nora O’Buck, RN-BSN, CCRNProgram Manager, Professional EducationEdwards Lifesciences

Maureen Spencer, M.Ed, BSN, RN, CIC, FAPICDirector, Clinical Implementation Accelerate Diagnostics

Pam Shirley, BSN RN, OCN, VA-BCClinical Nurse EducatorLa Jolla Pharmaceutical

Founding Sponsor: Network Sponsors:

• Nation’s leading sepsis organization, working in all 50 states

• Focus on:

• Public awareness

• Provider education

• Survivor support

• Advocacy

It’s About TIMETM, a national initiative

www.SepsisItsAboutTime.org

http://www.sepsisitsabouttime.org/

Did you know?

www.sepsis.org/shop

Best option: Amazon link on Sepsis Alliance website• Donation range of 4% - 8.5% on total monthly qualifying purchases

Amazon Smile program with Sepsis Alliance as your qualifying charity only 0.5% of qualifying purchases benefit Sepsis Alliance

Sponsor Innovation Webinar

Nora O’Buck, RN-BSN, CCRNProgram Manager, Professional EducationEdwards Lifesciences

Maureen Spencer, M.Ed, BSN, RN, CIC, FAPICDirector, Clinical Implementation Accelerate Diagnostics

Pam Shirley, BSN RN, OCN, VA-BCClinical Nurse EducatorLa Jolla Pharmaceutical

Founding Sponsor: Network Sponsors:

Sepsis Alliance WebinarNovember 19, 2018

Maureen Spencer, M.Ed, BSN, RN, CIC, FAPICDirector, Clinical Implementation

Accelerate Diagnostics, Inc.Tucson, Arizona

Sepsis Treatment

If sepsis is suspected:• Draw lactate

• Draw 2 sets of blood cultures (prior to antibiotic administration, if possible)

• Culture suspected site of infection (urine, wound, lower respiratory tract, etc.)

• Begin empiric antibiotic therapy

Gram positive coverage

+

Gram negative coverage

or or

+/-aminoglycoside

+/-

Yeast (Candida) coverage

+/-

Anaerobic Coverage for

abdominal infections

6 overnight incubation 7 colony selection 8 OPTIONAL: MALDI-TOF ID

.5 McFarland9 ID & susceptibility10 optimized therapy11

1 patient blood draw 2 blood bottle incubation & screening 3 perform gram stain 4 initial plate streaking 5 OPTIONAL: ID and resistance markers

Typical ID & AST Workflow

Blood culture incubation can be anywhere from 6-18hrs depending on lab and delivery into incubators

8-24hrs depending on lab

Time to ID/AST Results: 48-96 hours

Delayed Antibiotic Sensitivity Tests (AST) - #1

1Kumar et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical

determinant of survival in human septic shock. Crit Care Med. 2006 Jun; 34 (6 ):1589-96.

n = 2,731

Every hour of delay to optimal antimicrobial therapy for patients with severe sepsis decreases the chances of survival by 7.6%1

82%

77%

70%

61%

57%

50%

43%

32%

26%

19%

9%

5%

Ch

ance

of

surv

ival

Time to Appropriate Antimicrobial Rx following Onset of Hypotension

Clinical Urgency: Surviving Sepsis

>36hrs is when most blood

culture antibiotic sensitivity test

results are available from

standard lab procedures:

1) Delayed appropriate

treatment

2) Longer empiric antibiotic use

3) Delayed isolation for MDROs

Effect of Delayed Antibiotic Sensitivity Results in Healthcare

Antimicrobial Resistance - #2 Overuse of Antibiotics

“The CDC estimates that the direct costs of antimicrobial resistance on the U.S. economy is $20 billion annually. When you factor in the economic consequences of lost productivity, it adds an additional $35 billion in costs”

Resistance is Spreading Across CountriesA real global crisis – for

example:

December 2015

Pan-Resistant Enterobacteriaceae seen in

19 countries

mcr-1 >> Colistin resistant

• Plasmid mediated

• Easily passed between organisms

(E. coli/Klebsiella)

• Pan Resistance = No drugs work

https://www.cdc.gov/drugresistance/

CDC - Pathogen Distribution and Antimicrobial Resistance 2011-2014

infection control & hospital epidemiology January 2018, vol. 39, no. 1

C. difficile from Antibiotics - #3

17

Antibiotic Classes and Risk for C. difficile Infection

• Two meta-analyses found risk to be greatest with clindamycin, fluoroquinolones or cephalosporins

• 465 studies and included 5 published between 1994 and 2011 (total, 26,435 patients) in their meta-analysis1

• Risk for CDI to be more than tripled after any antibiotic exposure (odds ratio, 3.55).

• Treatment with clindamycin showed the strongest association with subsequent CDI (OR, 16.80)

• 910 studies and included 8 published between 2005 and 2011 (total, 30,184 patients)2

• Risk for CDI to be increased nearly sevenfold after antibiotic treatment (OR, 6.91)

• Risk was greatest with clindamycin (OR, 20.43), followed by fluoroquinolones (OR, 5.65), cephalosporins (OR, 4.47)

1. Brown KA et al. Meta-analysis of antibiotics and the risk of community-associated Clostridium difficile infection. Antimicrob Agents Chemother 2013 May; 57:23262. Deshpande A et al. Community-associated Clostridium difficile infection and antibiotics: A meta-analysis. J Antimicrob Chemother 2013 Apr 25

Emerging Technology:

Fast Antibiotic Sensitivity Tests (AST) to Reduce Empiric Use of Antibiotics

Fast Results• Identification in under 90 minutes using

Fluorescence In-situ Hybridization (FISH)

• Antibiotic Susceptibility with MICs reported

~5 hours after ID

• ~7 hours to microbiology report

Easy to Use• <2 min hands-on time

• Bring testing closer to the patient

• FDA cleared – Feb 23 2017

Accelerate PhenoTM System:

Direct from Positive Blood Culture

RBC Lysis Filtration Immobilization Microscopy Imaging

Module• Automated pipetting robot

• Digital camera

• Custom microscope

FISH Probes

Specimen Prep

System• 1-4 module(s)• Control & Analysis PCs• Touchscreen monitor

Identification MIC Susceptibility

Fast ID and AST BC System

+BC

Kit• 48 flow-channel cassette

• Reagent cartridge

• Sample vial

Gram-Positive + Yeast PanelCovers 90% of organisms responsible for BSIs

aCoagulase-negative Staphylococcus spp: Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus capitis, Staphylococcus lugdunensis, Staphylococcus warneri, not differentiated

bStreptococcus spp: Streptococcus mitis, Streptococcus oralis,Streptococcus gallolyticus, Streptococcus agalactiae, Streptococcus pneumoniae, not differentiated

Gram Positive ID

Am

pic

illi

n

Ceft

aro

lin

e

Ery

thro

myc

in

Dap

tom

yc

in

Lin

ezo

lid

Va

nc

om

yc

in

MR

SA

(Ce

fox

itin

)

ML

Sb

(Ery

thro

myc

in-

Cli

nd

am

yc

in)

Staphylococcus aureus O O O O O O O

Staphylococcus lugdunensis O O O O

Coagulase-negative

staphylococcia O O O O O

Enterococcus faecalis O O O O O

Enterococcus faecium O O O O O

Streptococcus spp.b O

Yeast

Candida albicans O

Candida glabrata O

Gram-Negative Panel

cKlebsiella spp: Klebsiella pneumoniae, Klebsiella oxytoca, not differentiated

dEnterobacter spp: Enterobacter cloacae, Enterobacter aerogenes, not differentiated

eProteus spp: Proteus mirabilis, Proteus vulgaris, not differentiated

fCitrobacter spp: Citrobacter freundii, Citrobacter koseri, not differentiated

Gram Negative IDA

mp

icil

lin

-

Su

lba

cta

m

Pip

era

cil

lin

-

Ta

zo

ba

cta

m

Cefe

pim

e

Ce

fta

zid

ime

Ceft

ria

xo

ne

Ert

ap

en

em

Me

rop

en

em

Am

ika

cin

Ge

nta

mic

in

To

bra

myc

in

Cip

rofl

ox

ac

in

Aztr

eo

na

m

Escherichia coli O O O O O O O O O O O O O

Klebsiella spp.c O O O O O O O O O O O O O

Enterobacter spp.d O O O O O O O O O O O O

Proteus spp.e O O O O O O O O O O O O O

Citrobacter spp.f O O O O O O O O O O O O

Serratia marcescens O O O O O O O O O O O O

Pseudomonas

aeruginosa O O O O O O O O O

Acinetobacter

baumannii O O O

Covers 90% of organisms responsible for BSIs

4 ID & susceptibility with MICs in ~ 7hrs

optimized therapy: de-escalate or escalate

51 patient blood draw 2blood bottle incubation & screening

Accelerate Pheno™ System = FAST Workflow

Incubation depends on the organism’s growth – typically from 6-18 hours

Place patients with MDROs

on isolation precautions at

~7hours

De-escalate or Escalate

empiric antibiotic

therapy

Benefits of the Accelerate PhenoTM System

• Standardizes laboratory procedures for BCs

• Allows clinicians to evaluate empiric antibiotic therapy faster and de-escalate or escalate therapy

• Reduces pharmacy costs for unnecessary antibiotics

• Improves care of patients with sepsis

• Reduces length of stay and days of antibiotic therapy

• Expedites isolation/precautions for multiple drug resistant organisms

• Decreases risk of C. difficile and MDROs

• Decreases use of antibiotics - prevents adverse side effects (ototoxicity, nephrotoxicity and acute renal injury, skin conditions, neurological effects

Is there Clinical Evidence???

Use of the Accelerate Pheno™ system, compared to SOC of VITEK® MS and VITEK® 2, resulted in:

• A statistically significant 3.0 day reduction in hospital (total) LOS

• A statistically significant 2.0 day reduction in antibiotic DOT (days on therapy)

• A statistically significant 36 hour reduction in TTOT

Accelerate PhenoTest™ BC Kit

Fast AST Results Improve Clinical OutcomesUniversity of Arkansas for Medical Sciences (UAMS)

Dare et al. Impact of Accelerate PhenoTM Rapid Blood Culture Detection System on Laboratory and Clinical

Outcomes in Bacteremic Patients. Presented as oral presentation at IDWeek 2018.

Clinical

Outcomes

Standard of Care

N=79

Intervention

N=75

p-value

LOS (days) 12.1 (11.9) 9.1 (7.6) 0.03

TTOT (hours) 73.5 (50.2) 37.5 (32.7) <0.001

Total Antibiotic DOT

(days) 9.0 (7.5) 7.0 (4.6) 0.05

Meropenem DOT

(days) 6.6 (3.7) 3.7 (2.1) 0.03

• The UAMS study demonstrated a 3-day LOS reduction following clinical implementation of the Accelerate Pheno™ system

• This suggests a mean cost savings of $6,565.50 per patient with bacteremia

Decreased LOS Improves Economic OutcomesImplications of UAMS’ 2018 Clinical Outcomes Study

“Hospital Adjusted Expenses per Inpatient Day by Ownership”. Henry J Kaiser Family Foundation. 2016. https://www.kff.org/health-costs/state-indicator/expenses-per-inpatient-day-by-ownership

1 inpatient day cost

3 inpatient days cost

Non-profit

hospitals $2,488 $7,464

For-profit hospitals $1,889 $5,667

A Kaiser Family Foundation report summarizes inpatient U.S. hospital costs in

2016 and indicates that the average cost was ~$2,200/day ($1,889 - $2,488).

7 publications

>30 posters/abstracts

31

Improving Operationsthrough simplified workflow for ID & AST results

Workflow may differ between laboratories

TYPICAL WORKFLOW ACCELERATE DIAGNOSTICS, Inc.WORKFLOW

Micro Lab

Infection

Prevention

Pharmacy

and ASP

Nursing and

Medical Staff

Infectious

Disease

Physicians

FAST ID & AST

CEO, CFO, COO,

CNO, CMO

Administration

Information

TechnologyImproved drug/bug

orders and

standardized order sets

Sepsis Alerts in EMR

Standardized

Blood culture

procedures

Improved

sensitivity and

MIC results

Improved

turnaround time

to ID/AST/MIC

Improved

bench

workflow

Reduction in BC contamination rates

Improved services

and staff utilizationSave lives

Reduction isolation

beds, PPE.

Improved bed

utilization

Reduction in

cases reported to

NHSN and CMS

Penalties

Reduction in

outbreaks

(MDRO,CDI)

Reduction in

MDROs, CDI,

cross

infection,

less isolation

Escalation or

de-escalation

Rapid transition to

targeted therapy

Reduced ABX cost:

prep, delivery

More efficient

ABX Stewardship

Program

Reduced morbidity/mortality,

reduced cost of care

Reduced Lab draws and drug

admin by RNs

More efficient use of ICU beds

and staff

Expedited transfers of +BC

patients back to LTACs

Efficient response to

sepsis alerts

Reduced

morbidity/mortality

Eliminates broad-

spectrum ABX use

Reduced use of

restricted ABX

Fast ID/AST Impacts Hospital Patient Care

Individualized Resuscitation: A new chapter for optimizing tissue perfusion

Nora O’Buck RN-BSN, CCRN

Disclosure

▪ Nora O’Buck is a paid employee of Edwards Lifesciences

Objectives

▪ Early resuscitation in sepsis

▪ Current guideline recommendations

▪ Goals of hemodynamic monitoring in sepsis

▪ Introduction of novel, non-invasive monitoring technology

38

Normal circulation vs septic shock patient

Images: Spronk et al. Nitroglycerin in Septic Shock After Intravascular Fluid Resuscitation. The Lancet. 2002.

Imaging of sublingual circulation

Early fluid resuscitation is associated with improved sepsis outcomes

39

Leisman D, et al. Association of fluid resuscitation initiation within 30 minutes of severe sepsis and septic shock: Recognition with reduced mortality and length of stay. Annals of Emergency Medicine 2016.

IV fluid resuscitation initiated within 30 minutes

decreased length of stay and improved mortality

CMS Sepsis Bundle Guides Treatment of Sepsis

Within 3 hours

1.) Measure lactate level

2.) Obtain blood cultures prior to administration of antibiotics

3.) Administer broad spectrum antibiotics

4.) Only if septic shock is present, administer 30 ml/kg crystalloid for hypotension or lactate ≥4mmol/L

Sepsis CMS Core Quality Measure (NQF #0500)

Hospitals reporting on sepsis treatment for FY17 payment determination

Within 6 hours

1.) Apply vasopressors

2.) Re-measure lactate if initial lactate elevated

3.) Re-assess volume status and tissue perfusion

In the event of persistent

hypotension that does not

respond to initial fluid

resuscitation

Severe Sepsis

CMS data collection begins

▪ Vital signs AND

▪ Cardiopulmonary exam AND

▪ Peripheral pulse evaluation AND

▪ Skin examination

All

▪ CVP

▪ ScvO2

▪ Bedside cardiovascular ultrasound

▪ Dynamic assessment of fluid responsiveness with passive leg raise or fluid challenge

Two of four

OR

NQF #500 Severe Sepsis and Septic Shock. National Quality Forum. Center for Medicare and Medicaid Services. 2015.

BMJ 2018/360:k703

Right Fluid for the Right Patient

❑ Prioritize immediate fluid resuscitation.20

❑ Recommended fluid volume in first hour: 30mL/kg.21

❑ A history of heart failure, liver failure, or renal failure

is not a contraindication to fluid resuscitation.22

Under and over-resuscitation of fluid is an

important concern in fluid management.23

ACEP DART Tool Recommendations

How do you know if you have given the right amount of fluid for your patient?

Bellamy Curve24

IVF in sepsis patients with heart failure or kidney disease

43

Liu V, et al. Multicenter Implementation of a Treatment Bundle for Patients with Sepsis and Intermediate Lactate Values. American Journal of Respiratory and Critical Care Medicine. 2016.

“Multi-center implementation of a

treatment bundle for sepsis patients

with intermediate lactate values

improved bundle compliance and

was associated with decreased

hospital mortality.

These decreases were mediated by

improved mortality and increased

fluid administration among patients

with a history of heart failure or

chronic kidney disease.”

Goal of Hemodynamic Monitoring in Sepsis

▪ Identify hemodynamic instability and its cause

▪ Monitor response to therapy

▪ Encourage timely clinical intervention to prevent and correct hypoperfusion

▪ Optimizing delivery and consumption of oxygen

44

Blood pressure alone does not reflect perfusion

45

1. Schwaitzberg, et al. A pediatric trauma model of continuous hemorrhage. J Ped Surg 1988

2. Hamilton, et al. Comparison of commonly used clinical indicators of hypovolaemia with gastrointestinal tonometry. Intensive Care Med 1997

3. Rackow, et al. Pathophysiology and Treatment of Septic Shock. JAMA 1991

4. Giglio, et al. Goal-directed haemodynamic therapy and gastrointestinal complications in major surgery: a meta-analysis of randomized controlled trials. BJA 2009

25-30%1,2,3

By the time hypotension occurs,

perfusion is compromised3,4

Determinants of blood pressure

46

MAP CO

HR

Preload Contractility Afterload

SV

SVR= X

X

Cannesson & Pearse. Perioperative Hemodynamic Monitoring and Goal Directed Therapy. 1st Edition Cambridge U Press 2014.

Darovic, G. Hemodynamic Monitoring: Invasive and noninvasive clinical application. Third Edition. Chapter 11, page 245.

Fluid Challenge

Fundamentally, the only reason to give a patient a fluid challenge is to increase SV. As preload increases, left ventricular SV increases until optimal preload is achieved, at which point SV remains relatively constant.32

Measure SV

Deliver fluid (200 - 250mL)

SV increase > 10% ?

YES

NO

Monitor SV

for clinical signs of fluid loss

SV change < 10% ? YES

NO

Initiate Bundle

Frank Starling Curve: Michard F. Changes in Arterial Pressure During Mechanical Ventilation. Anesthesiology. 2005.

Fluid Challenge: Johnson, Alexander. Stroke Volume Optimization: The New Hemodynamic Algorithm. American Association of Critical Care Nurses. 2015.

Assess Fluid Responsiveness Post Initial BolusStroke Volume (SV) helps to guide optimal fluid volume administration decisions for septic patient.

*Clinicians can use continuous monitoring to test fluid responsiveness with two challenges:

Smart. Innovation.

Over 40 years of helping you make more informed decisions to advance patient care

49

Introducing the ClearSight System

The ClearSight system is a simple noninvasive technology that provides continuous real-time

advanced hemodynamic information for critically ill patients.

Continuously Monitor

Advanced Parameters:

SV | SVV | SVR | CO | BP

The ClearSight System

connects quickly to the patientThe ClearSight system

provides real-time

hemodynamic information

Know More with Continuous Noninvasive Monitoring

Sepsis patients may present with widely diverse hemodynamic profiles. Knowing an individual

patient’s presenting hemodynamic measurements may provide targets for fluid resuscitation,

an important component of sepsis treatment.1

Reference

1. Nowak, Richard M,. Noninvasive Hemodynamic Monitoring in Emergency Patients with Suspected Heart Failure, Sepsis and Stroke:

The Premium Registry. 2014

Must act on information

52

Hemodynamic Monitoring Truth

No hemodynamic monitoring device will improve

outcome, unless coupled with a treatment, which

improves outcomes

Pinsky & Payen. Functional Hemodynamic Monitoring, Springer 2004

For more education on the ClearSight monitoring system, go to:

Edwards.com

[email protected]

Cell: 678-787-1467

mailto:[email protected]

Remember the MAP-Considerations in Distributive Shock

This presentation is a non-CEU event and is sponsored by La Jolla Pharmaceutical Company

Pam Shirley,RN,BSN,OCN,VA-BCClinical Nurse Educator

PM-US--0142

55

• Review types of shock and the incidence of distributive shock

• Discuss recommendation of a mean arterial pressure (MAP) target of 65 mm Hg

• Introduce the Renin Angiotensin-Aldosterone System as a treatment pathway for distributive shock

• Review ATHOS-3 study and introduce GIAPREZA, a novel vasopressor

Session Objectives

Objectives

56

MAP

Types of Circulatory Shock

Distributive shock leads to organ dysfunction and death due to hypotension

and insufficient tissue perfusion1

It is associated with high mortality2,3

1.2 million shock patients annually in the US4

MAP=mean arterial pressure.

1. Cecconi M et al. Intensive Care Med. 2014;40(12):1795-1815; 2. Singer M et al. JAMA. 2016;315(8):801-810; 3. Vincent J et al. N Engl J Med. 2013;369(18):1726-1734; 4. Vincent J et al. N Engl J Med. 2013;369(18):1726-1734 and Decision Resources Group market research

Adapted from

Vincent J-L et al.

New Engl J Med.

2013;369:1726-

1734.

Distributive shock(94% septic shock1)

Vasodilation

Cardiogenic shock

Ventricular

failure

Hypovolemic shock

Loss of plasma

or bloodvolume

66% 16%

16%

2%

Obstructive shock

Obstruction

Pericardialtamponade

57

Guidelines for Initial Resuscitation in Patients with Sepsis or Septic Shock

1. Rhodes A et al. Intensive Care Med. 2017;43:304-377.

Initial resuscitation guidelines

• At least 30 mL/kg of IV crystalloid fluid recommended within the first 3 hours

• An initial target MAP of at least 65 mm Hg in patients with septic shock requiring vasopressors

58

Catecholaminesa: sympathetic nervous

Vasopressin: arginine-vasopressin

Angiotensin II:

renin angiotensin-aldosterone

A Multimodal Approach to Increasing MAP

aCatecholamines include NE, epinephrine, dopamine, phenylephrine, ephedrine.

Current Therapies

SYMPATHETIC NERVOUS

ARGININE-VASOPRESSIN

RENIN ANGIOTENSIN-ALDOSTERONE

59

Renin ACE

Renin-Angiotensin-Aldosterone System

ACE=angiotensin-converting enzyme; Na+=sodium; H20=water.

Adapted from Hendry C et al. Nurs Stand. 2012;27(11):35-40.

Renin secreted by

kidneys, converts

angiotensinogen

to angiotensin I

ACE secreted by

lungs, converts

angiotensin I to

angiotensin II

Secreted by liver and

successively processed

into angiotensin II

Drop in blood pressure

Aldosterone

increases Na+ and

H20 reabsorption by

kidneys

Angiotensinogen Angiotensin I Angiotensin II

• Direct action on blood

vessels promoting

vasoconstriction

• Stimulates aldosterone

release from adrenal gland

Angiotensin II

raises blood pressure

60

GIAPREZA Indication

GIAPREZATM (angiotensin II) [package insert]. San Diego, CA: La Jolla Pharmaceutical Company; 2017.

GIAPREZA is a vasoconstrictor to increase blood pressure in adults with septic or other

distributive shock

61

GIAPREZA Studied in the ATHOS-3 Trial

Khanna A et al. New Engl J Med. 2017;377:419-430

• An international, multicenter, double-blind, placebo-controlled study with 344 randomized patients

ATHOS-3

Angiotensin II for the Treatment of High-Output Shock

62

ATHOS-3 Trial Design

aGIAPREZA and placebo were studied in conjunction with norepinephrine, epinephrine, dopamine, phenylephrine, and vasopressin.1

bTreatment allowed up to Day 7. Day 28 (± 2 days) follow-up determined safety events that occurred between Day 7 and Day 28.3,4

1. GIAPREZATM (angiotensin II) [package insert]. San Diego, CA: La Jolla Pharmaceutical Company; 2017; 2. Chawla LS. Crit Care Resusc. 2017;19:43-49; 3. Khanna A et al. New Engl J Med. 2017;377:419-430; 4. Khanna A et al. New Engl J Med. 2017;377:419-430 [Trial Protocol]

Adults with septic or other distributive shock who remained hypotensive despite fluid resuscitation

and standard of care vasopressor therapy were randomized to GIAPREZA or placebo1,2,a

ATHOS-3 trial design

1:1 double-blind

randomization

(N=321)1

GIAPREZA

and 1 or more standard of

care vasopressorsa

(n=163)1,2

Placebo

and 1 or more standard

or care vasopressorsa

(n=158)1,2

Primary endpoint1

MAP ≥75 mmHg or a ≥10 mmHg

increase, without an increase in baseline

vasopressor therapy at hour 3

Hour 3b

63

70% of GIAPREZA Patients Achieved Primary Endpoint1

aMAP response defined as an increase from baseline of ≥10 mm Hg or an increase to ≥75 mm Hg, without an increase in the dose of background vasopressors.

Modified intention-to-treat (mITT) population.

1. Adapted from Khanna A et al. New Engl J Med. 2017;377:419-430. 2. GIAPREZATM (angiotensin II) [package insert]. San Diego, CA: La Jolla Pharmaceutical Company; 2017.

114163

37158

In the GIAPREZA-treated group, the median time to reach the target MAP endpoint

was 5 minutes2,a

GIAPREZA Placebo

Higher incidence of thrombotic and thromboembolic events in patients who

received GIAPREZA2

64

GIAPREZA: Adverse Reactions


Patients with event, n (%)

GIAPREZA

N=163

Placebo

N=158

Thromboembolic eventsa 21 (12.9%) 8 (5.1%)

Deep vein thrombosis 7 (4.3%) 0 (0.0%)

Thrombocytopenia16 (9.8%) 11 (7.0%)

Tachycardia14 (8.6%) 9 (5.7%)

Fungal infection10 (6.1%) 2 (1.3%)

Delirium9 (5.5%) 1 (0.6%)

Acidosis9 (5.5%) 1 (0.6%)

Hyperglycemia7 (4.3%) 4 (2.5%)

Peripheral ischemia7 (4.3%) 4 (2.5%)

Adverse reactions occurring in ≥4% of patients treated with

GIAPREZA and ≥1.5% more often than in placebo-treated patients

aIncluding arterial and venous thrombotic events.

65

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

-2 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28

Days from randomization

Placebo

GIAPREZA

Treatment Day 28 est. (95% CI) Hazard ratio (95% CI) p value

Placebo 46.1% (38.2–53.7) 0.784 (0.574–1.069) 0.1229

GIAPREZA 53.9% (46.0–61.2)

0

Su

rviv

al p

rob

ab

ility

Mortality: 28-Day Survival

Adapted from Khanna A, et al. N Engl J Med. 2017;377:419-430.

n = 163 151 142 133 129 124 120 116 115 112 109 104 104 100 98 98 97 97 96

n = 158 140 129 122 115 111 105 104 100 96 93 91 88 86 84 79 77 77 77

95 94 94 94 93 93 91 90 86 61

77 76 74 74 73 72 72 71 70 58

mITT population

ATHOS-3 was not

powered for mortality

66

GIAPREZA: Specific Populations

aNo formal pharmacokinetic studies were conducted with GIAPREZA in this specific population.1


• The clearance of angiotensin II is not dependent on renal function.

• Therefore, the pharmacokinetics of GIAPREZA are not expected to be influenced by renal impairment

Renal Impairmenta

• The clearance of angiotensin II is not dependent on hepatic function.

• Therefore, the pharmacokinetics of GIAPREZA are not expected to be influenced by hepatic impairment.

Hepatic Impairmenta

• The effect of age was analyzed in the 163 patients receiving GIAPREZA in ATHOS-3.

• There were no significant differences in pharmacokinetics between age groups (< 65 years / ≥ 65 years)

Age

67

GIAPREZA: Contraindications and Drug Interactions

ACE – angiotensin converting enzyme; ARBs – angiotensin receptor blockers


• Concomitant use of ACE inhibitors may increase response to GIAPREZA

• Concomitant use of ARBs may decrease the response to GIAPREZA

Drug Interactions

• None Contraindications

68

GIAPREZA Summary


• GIAPREZA is the only available vasopressor

that utilizes the Renin-Angiotensin-Aldosterone

System (RAAS)

• 70% of patients treated with GIAPREZA

achieved target MAP at hour 3 versus 23% of

patients treated with placebo

• Concomitant use of ACE inhibitors may

increase the response to GIAPREZA

Concomitant use of ARBs may decrease the

response to GIAPREZA

• In the GIAPREZA-treated group, the median

time to reach target MAP endpoint was 5

minutesa

aMAP response defined as an increase from baseline of ≥10 mm Hg or an increase to ≥75 mm Hg, without an increase in the dose of background vasopressors.

Modified intention-to-treat (mITT) population

Sepsis Case StudiesNovember 27 at 2 pm ET

Webinar seriesSepsis: Across the Continuum of Care

This webinar series is made possible with support from bioMérieux, Inc.

Sepsis in Older AdultsDecember 18 at 2 pm ET

Sharon Hansen, MN, RN, CCRN Critical Care Nurse Educator MultiCare Health System

Lori Olvera, DNP, RNC-OB, EFM-CPerinatal Educator Sutter Medical Center

Rebecca Hancock, PhD, RN, CCRPatient Safety & Quality AdvisorIndiana Hospital Association

Register: www.sepsiswebinar.org

sponsor innovation webinar...sponsor innovation webinar nora o’buck, rn-bsn, ccrn program manager,...

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