A R andomiz E d Trial of - PowerPoint Presentation

Slide1

A

R

andomiz

E

d

Trial of

EN

t

ER

al

G

lutamine to

Minim

IZE

Thermal Injury:

A multicenter Pragmatic RCT (definitive study)

Study

Sponsor:

Dr

. Daren

Heyland

Clinical Evaluation Research Unit

Project Leader

: Maureen

Dansereau

European Partner

: Dr. Michael

Chourdakis

European Project Leader

: Eirini

Kasapidou

Slide2

Maureen

Michael

Eirini

Daren

Need photo of DKH here

Slide3

Slide4

www.criticalcarenutrition.com

Slide5

Double blind treatment

A

R

andomiz

E

d

trial of

EN

t

ER

al

G

lutamine to

minim

IZE

thermal injury

R

EN glutamine

Maltodextran

placebo

Concealed

Stratified by site

6 month mortality

2700 patients with

TBSA

≥ 20%, if 18-59 yrs age

≥ 15%, if 18-59 yrs age

with

inhalation injury

≥ 10%, if

≥

60 yrs age

Slide6

Why

are we

doing

this

trial?

Slide7

The Clinical Significance of Burn Injuries

Worldwide, burn injuries represent a significant public health problem.

Ranked the fourth most common injury.

Leading cause of disability adjusted life years in low and middle-income countries.

Mortality from burn injuries has plateaued and the leading cause of death from burn injuries continues to be sepsis and multiple organ failure.

Burn patients present with up to a 3-fold higher prevalence of sepsis than other trauma patients.

Slide8

The overall aim of the RE-ENERGIZE study is to reduce the burden of illness associated with significant burn injury using a naturally occurring substance, glutamine!

Slide9

Canada

:

8

United States:

32

UK: 4

Italy: 1

Serbia: 1

Greece:

3

Spain:

4

Switzerland:

1

Czech Republic: 2

Romania

: 1

Netherlands:

1

Portugal: 1

Total Sites:

70 sites worldwide!rSweden: 1Austria: 2

Belgium: 2Germany: 6

Slide10

<

72 h

(ACU admission to time of consent)

ACU Admission

Consent Obtained

Randomization

First Dose of IP

2 h

<

74 hours

Dosing until 7 d after last graft up to 3 m.

Mortality assessment

Data collection from ACU admission to 10 days after last graft up to 3 mos.

3 mos.

Maintain regular contact

SF-36 Quality of Life Assessment

Activities of Daily Living

Instrumental Activities of Daily Living

Employment Status Assessment

6 month

Study Overview

6

month

Slide11

Presentation Outline

Investigator Responsibilities

Patient Eligibility

Obtaining Consent

Randomizing a Patient

Central Randomization System (CRS)

Study Intervention

Nutrition Management

Outcomes

REDCap

(Electronic Data Capture System)

Data Collection and Data Entry

Slide12

Role

of the Site Investigator Delegation of Authority

Burn Grafting Assessments

SAEs

Investigator Responsibilities

Slide13

Ensure subject safety is protected & well-managed

Full compliance with requirements of Good Clinical Practice (GCP)

Conduct the study in compliance with the

protocol

Role of Site Investigator

Slide14

Acknowledge and retain responsibility for study conduct

Personally conduct or supervise the clinical study

Ensure

that all study staff are informed of their obligations (Delegation of

Authority)

Maintain records of staff qualifications

Ensure that mechanisms are in place to ensure that site staff receive the appropriate information throughout the

study

Ensure

that appropriate medical coverage is identified for any planned absences (holiday, attending a conference, etc

.)

Allow monitoring, auditing & regulatory inspections

Notify CERU asap

of any planned regulatory inspections

Interact with the

CERU

monitor during monitoring visits

Investigator Responsibilities

Slide15

Site Investigator/sub-I delegate must make the following determinations and sign/date applicable documents, whether in the patient chart or on a study specific form, to indicate he/she made the assessment:

Confirmation of patient eligibility

SAE Identification & Assessment

Ensure

adherence to reporting requirements & timelines

Provide causality assessment

Determine relationship to investigational

product

Severity of Burn and Grafting Assessments

Highlighted Responsibilities

Slide16

Delegation of Authority Logs

“The Investigator should maintain a list of appropriately qualified persons to whom the investigator has delegated significant trial-related duties”

(ICH section 4.1.5)

Complete log and send

to CERU

before

start of

trial.

Each team member to must be trained on the study before performing any

study

related, delegated tasks.

Slide17

Delegation of Authority Logs

Slide18

Assessments to be done

by the surgeon/physician

using the Lund and Browder chart

SI/sub-I must confirm

all

assessments

.

REMINDER:

Area expected to require grafting cannot be zero –

this is an inclusion criterion!

Initial Grafting Assessment

Slide19

Assessments to be done by

the

surgeon/physician and confirmed by the

SI/sub-I

Use the

Lund and Browder Chart

If Last Successful Graft was not achieved, indicate the reason

Final Grafting Assessment

Slide20

Initial Grafting Assessment

Deep Partial/Full Thickness Burn expected to require

grafting: __________%TBSA

Record only the %TBSA you expect to graft. This may be a small percentage of the total burn size. There is no minimum, however this cannot be zero and should not be greater than the total burn size.

Final Grafting Assessment

Total Body Surface Area that actually required grafting: __________%TBSA

Record the %TBSA you actually grafted. This may be zero if the patient healed without needing an expected graft. There is no minimum or maximum, however this should NOT be 100%.

GRAFTING

ASSESSMENTS: Important Note

Grafting assessments are record as percent Total Body Surface Area (%TBSA).

Slide21

Lund and Browder chart

Slide22

Any

untoward medical event that:

Results

in death,

Is life-threatening,

Requires hospitalization or prolongation of hospitalization,

Results in disability/incapacity,

Is a congenital anomaly/birth defect,

A medically important event

(e.g. one that may result in an intervention to prevent one of above outcomes)

Serious Adverse Events (SAEs)

Slide23

Given the high acuity of diseases and morbidity related to burns,

adverse events are NOT

to be reported to CERU,

only report

Serious

Adverse Events (SAEs)

.

SAE: Adverse and Serious

Life threatening

Prolongs Hospital Stay

Results in persistent or significant disability/incapacity

Requires medical or surgical intervention

Congenital anomaly/birth defect

Other serious medical event

Serious Adverse Events (SAEs)

Slide24

Unexpected event

- is

NOT expected due to the progression of the underlying disease or co-morbid illnesses

.

Example

:

Seizure in the absence of seizure disorder

Not all deaths – only unexpected

.

Related

to the Study

Intervention

defined as:

Possibly Related

: suggests that the association of this SAE with the study supplement is unknown and the event is not reasonable supported by other conditions.

Probably Related

: suggests that a reasonable temporal sequence of this SAE with study supplement administration exists and the association of the event with the study supplement seems likely.

 

Report SERIOUS Adverse Events that are: 1. Unexpected – regardless of relationship to intervention2. Related to Intervention – regardless of expectedness

SAE Identification

Slide25

Do not report

death as an SAE.Death – is an outcome not an event

If a reportable SAE results in death, record death as the outcome and the underlying cause of death as the SAE.

Not all deaths needed to be reported

Do not report

expected

events that lead to death

.

Example

:

Patient with severe burns develops sepsis and dies. It is not unexpected and thus does not need to be reported to CERU.

NOTE

: please follow local ethics requirements for reporting death and adverse events

SAEs:

Death

Slide26

The relationship of the study intervention

to the SAE must be determined by SI

Refer to the definitions below when determining relatedness:

SAE

RELATIONSHIP TO INTERVENTION

Slide27

Worksheets are provided to assist with data collection.

SAEs must be

completed in

REDCap

™

within 24 hours of becoming aware of the event

.

SAE

Worksheets

Slide28

Remember to

de-identify

any supporting documentation that is scanned or faxed to the central study team.

SAE

Worksheets (cont.)

Slide29

You may report up to 3 SAEs per day in

REDCap

.

If you have more than 3 SAEs to report on any given day,

contact the Project Leader.

Click

on the down error in the box on the grid on the specified day to

reveal SAE forms.

Record

SAEs on the grid on the day the SAE occurred, not the day you are reporting it.

SAEs

in

REDCap

Slide30

Return to the same form to update data as it becomes available.

Indicate the report status as updates are provided.

SAEs

in

REDCap

(cont.)

Slide31

A subject may be withdrawn from IP at any time:

at Substitute Decision Maker

or

her/his

own request, or

at the discretion of the investigator for safety, behavioral or administrative reasons.

A subject may withdraw (or be withdrawn) from the study prematurely for the following reasons:

•

Serious Adverse Event related to intervention

•

Termination

of the study by the sponsor

•

Other

(must be specified)

Subject Withdrawal

Slide32

Patient Eligibility

Inclusion criteria

Exclusion criteria

Inhalation Injury

Co-Enrollment

Using your judgement

Slide33

Deep 2nd and/or 3rd degree burns requiring skin grafting*.

*Note: there is no minimum area that requires grafting.

As long as the total burn size meets the inclusion criteria and a graft is

required, the patient is eligible.

One of the following:

Patients 18 – 59 years of age with a TBSA ≥ 20%

Patients 18 – 59 years of age with a TBSA

>

15 % WITH

a

n inhalation injury*

Patients

>

60 years of age with a TBSA ≥ 10%.

Diagnosis

of

*inhalation

injury requires both of the following:

   

1

) history of exposure to products of combustion   2) bronchoscopy revealing one of the following below the glottis evidence of carbonaceous material signs of edema or ulcerationInclusion Criteria

Slide34

Definitive Study:

Exclusion Criteria

>72 hrs from admission to ACU (Acute Care Unit) to time of consent

(>24 hrs from injury to admission also excluded – in SPM)

Patients younger than 18 years of age

(age of maturity for an eligible patient to obtain consent is 18 years in Canada and in the US)

In patients without known renal disease, renal dysfunction defined as a

serum creatinine >171

μ

mol

/L or >1.93 mg/

dL

or

urine output of less than 500 ml/last 24 hours (or 80 ml/last 4 hours if a 24 hour period of observation is not available).

In patients with acute on chronic renal failure (pre-dialysis), an absolute increase of >80

μ

mol

/L or >0.9 mg/

dL from baseline or pre-admission creatinine or a urine output of <500 ml/last 24 hours (or 80 ml/last 4 hours) will be required. Patients with chronic renal failure on dialysis will be excluded.

Changed to REDOXS criteria to address reviewer’s concerns

Slide35

4. Liver cirrhosis -Child’s class C liver disease

5. Pregnancy (urine/blood tests for pregnancy will be done on all women of childbearing age by each site as part of standard ACU practice)

6. Contra-indication for EN:

intestinal occlusion or perforation, intra-abdominal injury

7. Patients with injuries from high voltage electrical contact

8. Patients who are moribund (not expected to survive the next 72 hours)

9. Patients with extreme body sizes: BMI < 18 or > 50 kg/m

2

10. Enrolment in another industry sponsored ACU intervention study (co-

enrollment

in academic studies will be considered on a case by case basis)

11. Received glutamine supplement for > 24 hrs prior to randomization

12. Known allergy to maltodextrin, corn starch, corn, corn products or glutamine

Also exclude patients you judge not able to follow up at 6 months

(e.g. illegal aliens, homeless, etc.)

Definitive Study:

Exclusion

Criteria

Slide36

Obtaining Consent

Informed Consent: ICH Definition

Communication

Location

Time for Questions

Signature and Date

Documentation

Slide37

ICH Definition of Consent

“A process by which a subject voluntarily confirms his or her willingness to participate in a particular trial,

after having been informed of all aspects of the trial that are relevant to the subject’s decision to participate. Informed consent is

documented

by means of a

written, signed and dated

informed consent form.”

What is Informed Consent?

Slide38

Treating physician/delegate

provide update on patient’s condition to SDM (Substitute Decision Maker)

Physician

/delegate

introduce RC to SDM

to discuss consent

RC

find a quiet, private location to review study details

with SDM

Fully inform

SDM

of all aspects of the study

Assess

if language barriers

–

enlist a translator

if necessary

Do Not coerce

SDM to provide consent for patient to participate

Provide a copy of the ICF to SDM and

allow time to readAsk questions to ensure SDM understands Sign and obtain SDM signature on ICFRecord date and time consent was obtainedProvide SDM with a copy of the signed ICFDocument consent & file copy of signed ICF in patient’s medical chartFile original signed ICF with the study-related documentation Consent Procedures for RE-ENERGIZE

Slide39

Document patient participation in the medical chart, including:

Study Name

Eligibility was confirmed

Physician who confirmed eligibility (must be on the Delegation Log)

Date and Time consent was obtained

Who provided consent (patient, spouse, child, etc.)

Who obtained consent (PI, sub-I, nurse, etc.), signed & dated

Documenting consent obtained

Slide40

After obtaining consent, get the Contact Information Form completed.

This will aid in obtaining 6 month follow-up data.

Collect as much contact information as possible

6 Month mortality is the

Primary Outcome

Contact Information

Slide41

Randomizing a Patient

Central Randomization System (CRS)

Access and Login

CRS as a Screening Log

Form Completion

Eligible bit Not Consented

Randomization Confirmation

Slide42

CRS

Access Log

Complete the CRS access Log

Send

completed log to CERU

(via

email preferred

)

Each

study team member needs

her/his own

login.

Do not share.

Slide43

Access the CRS

(Central Randomization System)

at:

https://ceru.hpcvl.queensu.ca/CRS/

.

You

will

receive an email with your username and temporary password

after

the completed CRS Access Log is received

CRS

Login

Login to enter screening

data and randomize patients.

Slide44

Enter

all screened patients, who meet the inclusion criteria into the CRS:Even

if they meet an exclusion criteria

Even

if you did not get consent

CRS Screening: who to enter

Slide45

After

you Login, you will see a list of studies you are participating in with CERU using the CRS:

Click on

“

RE-ENERGIZE – Definitive”

CRS Home Screen

How to Randomize your patient

Slide46

To enter data for a new patient,

select

“

Add patient”

Hid

e

CRS: Adding

a Patient

Slide47

Click

Inclusion Criteria

and complete the fields in the form

When you click the ‘Save’ button you will be taken to the next form

CRS:

Inclusion

Criteria

Slide48

Complete the exclusion criteria form

CRS:

Exclusion

Criteria

Slide49

CRS: Pre-Randomization

If the patient is eligible and Patient/SDM was not approached for Consent

Indicate the

primary

reason you did not approach for consent

Slide50

If you approach for consent and consent is

NOT obtained

Indicate the primary reason consent was not obtained

CRS Pre-Randomization

Slide51

When consent

IS obtained, complete the Pre-Randomization form

Enter Times per

24-hour

clock. If time is before 10:00, you must enter a leading zero.

Enter dates in

YYYY-MM-DD

format, or click in the date box to open the calendar

CRS Pre-Randomization

Indicate if height and weight were ‘measured’, ‘estimated’, or you don’t know how they were obtained

Slide52

After clicking ‘Save’ on the bottom of the Pre-Randomization form,

you will receive a Randomization Confirmation

Print the page

File it with your study records

Contact your pharmacy

CRS Randomization Confirmation

Slide53

Randomization and Screening Numbers

Every patient entered into the CRS will have a

Screening Number

Each patient randomized will

also

have a

Randomization Number

Number format:

First 4 digits = your site number

5

th

alpha character indicates Screened or Randomized

Last 3 digits = ascends sequentially starting with 001

Screening and randomization numbers advance independently

Example in the table above

:

Screening #:

1002Q006

Randomization #:

1002R003

This is the 6th patient screened and 3rd randomized

“Q” = Screened“R” = Randomized1002 - R- 001 Site# Patient#

Slide54

This page lists

all

patients screened and randomized

at your site

.

Site Status Page

To view any patient in the list, click on the corresponding:

Screening ID or

Status

Slide55

Indicates the status of each data entry form for the patient

Status

Symbol

Description

Completed

All

data has been completed and saved.

Not

Completed

Data

has not yet been entered on the

form

.

Locked

The

patient has been randomized and the data is

locked (no

longer able to be edited by the site

user).

Patient Status Page

Slide56

Investigational Product (IP)

Supply and package appearance

Dosing

Study Orders – sample documentation

Mixing and Administration

Making up Missed Doses

Changing the Prescription

Slide57

Investigational Product

The glutamine and maltodextrin

will be shipped to you

in 5g packets with blinding labels applied.

You will need

an

unblinded

team member

(pharmacy/delegate) for IP accountability and dispensing.

OR

MALTRIN® Maltodextrin

Slide58

MALTRIN

®

Maltodextrin

cool, dry area, below 32 C (90 F)

Storage and Temperature Logs

The temperature in the IP storage area should be documented everyday. If IP is stored in an area where temperature is monitored, duplicate documentation is not required.

Sample Temperature log available

Product must be stored at controlled room temperature

cool

, dry area, 25

C (77 F)

excursions allowed 15-30 C (59-86F

)

Slide59

Temperature recorded in (circle one) Celsius Fahrenheit

 

Date

Temperature

Initials

Comments

Date

Temperature

Initials

Comments

 

16

 

 

 

1

 

 

 

 

17

 

 

 

2   

 18   3

 

 

 

 

19

   4

 

 

 

 

20

 

 

 

5

 

 

 

 

21

 

 

 

6

 

 

 

 

22

 

 

 

7

 

 

 

 

23

 

 

 

8

 

 

 

 

24

 

 

 

9

 

 

 

 

25

 

 

 

10

 

 

 

 

26

 

 

 

11

 

 

 

 

27

 

 

 

12

 

 

 

 

28

 

 

 

13

 

 

 

 

29

 

 

 

14

 

 

 

 

30

 

 

 

15

 

 

 

 

31

 

 

 

Site Name ___________________________________________________ Site # _____________

Investigational Product is to be

stored

in a cool dry area

15°- 30° Celsius / 59°- 86° Fahrenheit

.

Record temperature daily.

Provide comment for days temperature is not recorded.

Keep this log with study IP documents. To be provided to Central Pharmacy Manager/

Unblinded

Monitor upon

request.

Month _____________________ Year ______________

sample Temperature Log

Slide60

Dosage

=

0.5g/kg/day

of

Dosing

Weight

Based on pre-burn dry weight

Adjusted for patient’s with BMI

>

35 kg/m

2

Rounded to the nearest 5g

(for dispensing)

IP Dosing and Administration

BMI

>

35 weight will be adjusted based on a BMI of 25 using the following formula:

Adjusted

Body Weight (ABW) =

IBW (Ideal Body Weight) + [(pre-burn dry weight – IBW) x 0.25]

Administration schedule:q4h as a bolus via small bore feeding tube (preferred) or a larger bore gastric/Levine tubeTID or QID via the oral route

Slide61

Quick Reference Dosing Chart

Dose #

1

2

3

4

5

6

q4h

Body weight (kg)

Number of 5g doses

Total

doses

g/day

35-44

1

0

1

0

1

1

4

20

45-54

1

1101

1

5

25

55-64

1

11

1

1

1

6

30

65-74

2

1

1

1

1

1

7

35

75-84

2

1

1

2

1

1

8

40

85-94

2

1

1

2

1

2

9

45

95-104

2

1

2

2

1

2

10

50

105-114

2

2

2

2

1

2

11

55

115-124

2

2

2

2

2

2

12

60

125-134

3

2

2

2

2

2

13

65

135-144

3

2

3

2

2

2

14

70

Slide62

Sample Study Order

Ensure the

order is signed

by the Site Investigator or sub-I

Document Study Orders in the Chart

Slide63

IP: Dispensing and Initiation

Contact the Pharmacy delegate

as soon as the patient is randomized

Provide the patient Randomization number

Pharmacy staff will access the CRS to view treatment allocation and dispense initial dose

IP is dispensed in 5g packets

IP is reconstituted and administered bedside by the clinical staff

IP should be initiated even if enteral nutrition has not been started

Administer IP within 2 hours after randomization

Slide64

Each 5g packet should be mixed with a

minimum

50 mL of *water or other non-heated liquid or food, such as:

Chocolate Milk

Yogurt

Applesauce

Cereal

Mashed Potatoes

Do

NOT

mix IP with soda or highly acidic juices (

grapefruit juice, orange juice, lemonade

). The IP degrades or becomes unstable in an acidic medium

*When mixing in water, use either sterile or tap water, per your standard procedure for mixing enteral formulas.

IP Mixing and Administration

Slide65

Interrupted or Missed Does of IP

IP should be treated as a medication

If at all possible, IP should continue as ordered through procedures or surgery

In the event of an interruption or missed doses, you should

make up the missed doses on the same calendar

:

Give additional doses

– at least one hour apart

(

There must be at least one hour between dose administration)

Double scheduled doses

(Do not give more than double the prescribed dose at one time)

Do Not stop IP for procedures or surgery

Slide66

Step by Step IP administration procedures

Place a copy at each study patients bedside

Administration Procedures

Slide67

Administration

Procedures (cont.)

Slide68

Glutamine may contribute to

elevated urea levels

in patients

with renal dysfunction who are not on dialysis.

If patient is on

dialysis

, study intervention

should NOT be held or discontinued

, regardless of Urea or Cr levels.

The clinical team may choose

to hold the study

intervention if:

t

he team is uncomfortable with the urea level AND

t

he patient is not to be dialyzed on the same calendar day

Recommended Guideline

for holding intervention:

Urea/BUN >21.5

mmol

/L or >60 mg/dLRestart study intervention when urea is below the threshold for holding intervention (above), at the discretion of the clinical team. IP Adjustments: Renal Dysfunction

Slide69

IP Dosing Changes

IP is based on the patient’s pre-burn dry weight

Patients will remain on the initially calculated dose of IP for the duration of the study, with one exception:

EXCEPTION:

If the patient has a change in body weight sufficient for the clinical team to alter dosage of clinical treatments, the study treatment dose should be adjusted as well.

IP does change is triggered by the clinical team changing the weight used to dose clinical treatments. Examples of events that may trigger a change in IP dosing weight:

Amputation

Greater than 10% weight loss

Notify the pharmacy of any changes in IP dosing weight

Document changes in the patient chart

Slide70

The following tasks are all a part of managing the nutrition received by each of your patients:

Utilizing the Standardization of Nutrition Practices

Assessing Energy needs upon admission to Acute Care Unit (ACU)

Assessing Protein needs upon admission to ACU

Prescribing daily Calories and Protein goals

Assessing Vitamin and Mineral intake and supplementation

Ensuring Glutamine and Arginine supplements are

not

given

Optimizing Enteral Nutrition Delivery

Monitoring & Recording Daily Nutritional Adequacy

Nutrition Management

Slide71

To reduce the effect of varying nutritional practices as confounding factors on the outcomes of The RE-ENERGIZE study, it is important to standardize (as much as possible) the following:

Prescription of

Enteral

and

Parenteral

Nutrition

Micronutrient delivery

Withholding Feeds for High Gastric Residual Volumes

We recommend compliance with the following nutritional practices.

This will allow for most current practices to continue.

Standardization of Nutrition Practices

Slide72

Calculated by using :

Indirect Calorimetry, a predictive equation, or a simple weight-based formula

On average, this should not lead to a prescription of less than 30 kcal/kg

 

Weight

Pre-burn dry weight

should be used when calculating energy needs.

For patients with a

BMI

>

35

kg/m

2

,

if your standard practice is to adjust for obesity, follow your standard practice. If you do not have an obesity adjustment practice, use the formula below.

Adjusted Body Weight (ABW) = Ideal Body Weight (IBW) based on a BMI of 25 + [(pre-burn dry weight – IBW) x 0.25]

1

) Prescribed Energy Needs

Standardization of Nutrition Practices

Slide73

Calculated

According to % body surface area burn

If

>

50% burns, use 1.5g/kg/day to 2.5g/kg/day

If < 50% burns, use 1.2g/kg/day to 2 gm/kg/day

 

Pre-burn dry weight

should be used when calculating protein needs.

For

o

bese patients

, if your standard practice is to adjust for obesity, follow your standard practice. If you do not have an obesity adjustment practice, use the formula below.

Adjusted Body Weight (ABW) =

IBW

(BMI 25)

+ [(pre-burn dry weight – IBW) x 0.25]

 

Standardization of Nutrition Practices

2) Prescribed Protein Needs

Slide74

Should be given as follows or depending upon blood levels (if blood testing is done as part of routine practice):

Vitamin C: 0-1000 mg/day

Vitamin A: 0-10,000 IU/day

Vitamin D: according to serum levels

Vitamin E: 0-420 mg/day

Zinc (not elemental): 0-220 mg/day

Copper

Sulfate

: 0-4.5 mg/day

Selenium: 0-500 micrograms/day

Magnesium:0-600 mg/day

Folate

: 0-1500 mg/day

Thiamin

: 0-110 mg/day

Standardization of Nutrition Practices

3) Vitamin & Mineral Prescription

Slide75

Early supplementation by high dose IV Vitamin C (66 mg/kg/hr) within the first 48 hrs is allowed. Standard multivitamin/mineral preparations are allowed (IV, NG or

po

).

These ranges of vitamins/minerals/trace elements may be provided as supplementation over and beyond what is present in the standard enteral/parenteral nutrition.

OR

These ranges of vitamins/minerals/trace elements may be

provided as the total amounts. This means that the amounts received from

enteral/parenteral

nutrition are to be subtracted from the total ranges and the remainder is given as supplements.

Standardization of Nutrition Practices

3) Vitamin & Mineral

Prescription (cont.)

Slide76

Arginine

enriched

formulas (formulas that contain >6gms

arginine

/L)

Pivot

®

(13 g/L)

Perative

®

(8 g/L) would not be allowed

 

Glutamine

supplements

or

formulas

enriched with glutamineImpact ® Glutamine (15 g/L)VIVONEX ® Plus (13.5 g/L)GLUTASOLVE ® (15 g/L) /other glutamine powdersJuven®

(7 g/L)Formulas with glutamic acid inherently present are allowedTo minimize any potential contamination, patients that have receivedglutamine for >24 hrs before randomization, should NOT be included.

Standardization of Nutrition Practices 4) Specialized nutritional formulas are not allowed such as:

Slide77

Enteral

nutrition is preferred over

parenteral

nutrition

Minimize interruptions to the delivery of EN – use strategies such as:

Elevating the Head of the Bed

Gastric residual volume threshold of 250 ml

Motility agents

Small bowel feeding tubes

Monitor EN volume delivery daily

Implement an action plan to ensure prescription is delivered

Standardization of Nutrition Practices

5)

Optimization of the Delivery of Enteral Nutrition:

Slide78

Slide79

Encourage the use of a

glycemic

control protocol (or insulin) to:

Avoid

hyperglycemia

Minimize risk of iatrogenic

hypoglycemia

Maintain glucose levels between the following ranges:

80 mg/

dL

(min) to 180 mg/

dL

(max)

4.4

mmol

/L (min) to 10

mmol

/L (max)

Standardization of Nutrition Practices

6) Glycemic control:

Slide80

Record Energy and Protein Needs

Record Timing of

Start and Stop of EN & PN

Slide81

If the patient’s energy and protein needs change



record the date and new prescription.

Record up to 6 Prescriptions

Slide82

Case Report Form worksheets provided to aid in data collection

Slide83

Collect and record daily nutrition

received

Review nutrition intake daily so action can be taken to ensure patient receives prescribed

nutrition

Slide84

ENTERAL NUTRITION:

If EN was not

received,

indicate

all

of the reasons (see list below):

NPO for endotracheal

extubation

or intubation or other bedside procedure

NPO for operating procedure

NPO for radiology procedure

High NG drainage

Increased abdominal girth, abdominal distention, or patient discomfort

Vomiting, emesis, or nausea

Diarrhea

No enteral access available/enteral access lost, displaced, or malfunctioning

Inotropes, vasopressor requirement

Patient deemed too sick for enteral feeding

On oral feeds

Reason not known

Other, please specify: __________________ Daily Nutrition:Enteral Nutrition (EN)

Slide85

If

EN was received

:

Record the name of the formula(s) given

Record up to 3 formulas each day. If more than 3 formulas were given, enter the 3 that provided the most volume

Record the total kcals received from EN

Record the total grams of protein received from EN

Daily

Nutrition:

Enteral Nutrition (EN) (cont.)

Slide86

If a

Protein Supplement was received

:

Record the name of the protein supplements given

Record the total kcals received from the protein supplement

Record the total grams of protein received from

the protein supplement

Daily

Nutrition

:

Protein

Supplements

Slide87

If

PN was

received

:

Record the total kcals received from

PN

Record the total

grams of protein

received from

PN

If

Propofol

was

received for

>

6 hours

:

Record the total volume (mL) of

Propofol

received

If Oral Nutrition received:Record that oral nutrition was receivedDaily Nutrition:PN, Propofol, Oral Intake

Slide88

If oral nutrition was given, indicate the

adequacy of intake via the oral route

:

Daily Nutrition:

Oral Intake percentages

Slide89

Primary

Outcome:

6

month

mortality

Secondary

Outcome

: Time

to

discharge

alive

Health-

related

quality

of life

(SF-36 @ 6 months)Incidence of acquired bacteremias due to Gram negative organismsHospital Mortality

Duration of mechanical ventilationACU stay and hospital stay Teritiary

Outcomes:Outcomes

Slide90

6 Month Survival

6 Month Mortality is the

Primary

Outcome

of

this Study

It is vital that

EVERY

resource possible is used to obtain the 6 Month Survival Status of each study Patient

If survival status is not obtained, please complete the form to confirm all attempts were made to obtain the information.

Slide91

Use the contact log to record all attempts to contact the patient and document completion of the 6 Month Follow-up Questionnaires

Contact Log

Slide92

Following data are recorded on the Hospital Overview form:

ACU discharge information

Hospital discharge information

If deceased –death date, time, & cause of death

Hospital Overview

Slide93

Record ACU

readmission

until

3 months post ACU

admission

to a maximum

of 5 admissions (including the initial admission)

Hospital

Overview

(cont.)

Slide94

Note

:

Do 

not

 record episodes of temporary ventilation

(defined as < 48 hrs)

Stop date

:

Record actual stop date or mechanical ventilation up to study day 90 in the ACU.

If transferred to another institution vented,

record transfer date

as ventilation stop date.

Slide95

Record

ONLY

Gram negative

bacteremias

from venous or arterial blood.

Date (

yyyy

-mm-

dd

)

 

 

 

 

1) Time (

hh:mm

)

-Gram Negative Culture Number(s)

 

2) Time (

hh:mm

)

-Gram Negative Culture Number(s)

 

3) Time (

hh:mm

)

-Gram Negative Culture Number(s)

 

4) Time (

hh:mm

)

-Gram Negative Culture Number(s)

 

Do not

record results

from catheter line tip specimens

MICROBIOLOGY

Slide96

Do NOT

record Gram Positive bacteria

Gram Negative bacteria

Slide97

SF-36

ADL (Activities of Daily Living)IADL (Instrumental Activities of Daily Living)

Employment Status Assessment

The following questionnaires are completed 6 months after ACU admission +/- 2 weeks:

Questionnaires may be administered via a telephone call or in person.

Keep the completed questionnaires with your study documents.

Questionnaires may be completed over several calls or visits if necessary.

NOTE:

Late data is better than missing data

.

Please make every attempt to complete the questionnaires, even if outside of the time parameters.

6-Month Follow-up Assessments

Slide98

Read each question and the response options to the patient.

Mark the patient’s response in the corresponding box.

SF-36

Slide99

SF-36 (cont.)

Slide100

SF-36 (cont.)

Slide101

SF-36 (cont.)

Slide102

SF-36 (cont.)

Slide103

Katz ADL

Slide104

Record the patient’s

highest

functional level.

What is the patient able to do?

Example:

If the patient does not do the laundry, but is able, indicate her/his level of ability.

Lawton IADL

Slide105

Data collected to compare pre- and post-burn employment status, and occupation.

Employment Status

Slide106

Employment Status (cont.)

Slide107

Employment Status (cont.)

Slide108

Employment Status (cont.)

Slide109

Employment Status (cont.)

Slide110

Employment Status – occupation list

Slide111

The following table provides a variety of patient outcome scenarios and a guide to which 6 month follow-up forms need to be completed.

Guide to 6 month Follow-up forms

Slide112

Data Collection and Entry

Protocol Violations

Data Collection and Entry:

REDCap

Slide113

DATA COLLECTION

REDCap

™

(Electronic Data Capture System)

REENERGIZE - Definitive

Access

REDCap

™ at the following web address:

https://ceru.hpcvl.queensu.ca/EDC/redcap

/

Slide114

Data

MUST

be collected according to calendar day as described

above

Do

NOT

collect data according to your flow sheet unless it runs from

00:00-00:00

Study days are defined as follows and data

must

be collected according to study days

:

Example

:

A patient is admitted to the ACU on Sept 8th, 2015 at 4:00 PM (16:00). The study days would be:

 Study Day 1 = 2015-09-08 from 16:00 to 2015-09-08 at 23:59

Study Day 2 = 2015-09-09 from 00:00 to 2015-09-09 at 23:59

Study Day 1

=

ACU admit date

(not randomization) and time until 23:59 the same day.Study Day 2 = the subsequent day starting at 00:00 to 23:59 that dayStudy Days and Data Collection

Slide115

REDCap

is the data capture system for the study

Worksheets are provided to assist in collecting the date to be entered.

DATA COLLECTION

Slide116

Randomized patients auto-populate in

REDCap

.

After randomization of the first patient, you will need to enter the lab units for your site

DATA ENTRY SCREEN

Slide117

After your first patient has been randomized:

Select Arm 2

and enter

lab units

LABORATORY UNITS ENTRY

Slide118

A grid with only one dot will display

Select the units each of the 9 labs are reported in at your site

Record Lactate from arterial blood

LABORATORY UNITS GRID

Slide119

General

Instructions

Complete all of the information by placing a

√

in the appropriate box.

Duration of

Data Collection

These data are to be collected once, at baseline.

Laboratory Units

Indicate the units each laboratory test is reported in by placing a

√

in the appropriate box.

T-

bilirubin

mg/

dL

µ

mol

/L

Glucose

mg/

dL

µmol/L Lactate

mg/dL µmol/L mEq/L

Ammonia

µg/

dL

µ

mol/L

Urea

 

mg/

dL

µ

mol

/L

Platelets

10^3/µL

10^9/L

Serum

Creatinine

mg/

dL

µ

mol

/L

Albumin

g/

dL

g

/L

WBC

10^3/µL

10^9/L

LABORATORY UNITS worksheet

Slide120

PATIENTS AUTOMATICALLY POPULATE

Select a patient from the dropdown list

Slide121

Click on any dot to open the corresponding form

EVENT GRID

Slide122

EVENT GRID – NAVIGATING THE TABS

Slide123

Outcomes and 6 Month Follow-up forms, including Survival Assessment are on the grid after Day 90.

Click on the 3

rd

tab at the top of the grid and scroll all the way to the right to find and complete these forms

EVENT GRID – AFTER DAY 90

Slide124

eCRF

worksheets

-

are

to assist you in collecting required data

Medical Chart

- is the

source document

Exception

:

6 Month Follow-up Questionnaires worksheets are the source documents –

need to keep

Instructions

-

are in the

eCRF

worksheets and must be reviewed

Data Entry

- is done in REDCAP™ and forms may look differentWorksheets and Instructions     

Electronic Case Report Form (eCRF)

Slide125

Inhalation Injury

Diagnosis requires

:

1) history of exposure to products of combustion

2) 

bronchoscopy

revealing one of the following below the glottis

Evidence of carbonaceous material

Signs of

edema

or ulceration

Slide126

High Dose

Vitamin C as part of Resuscitation

Common practice is:

66 mg/kg/

hr

for the first 24–48 hours

(above is a guide

not

a requirement)

Do not report standard Vitamin C dosing

Slide127

Select comorbidities from the list provided.

If no comorbidities per the list, check “No Comorbidities”

Slide128

Hx

of Alcohol Abuse

Record Alcohol Abuse as a comorbidity IF documented in the patient’s medical chart.

Slide129

MAP

(if not available)

Calculation: 1/3 lowest systolic BP + 2/3 corresponding diastolic BP

Web link:

http://www.mdcalc.com/mean-arterial-pressure-map

/

Collected

once

at baseline

Slide130

Date and Time

first

dose of

s

tudy

i

ntervention

a

dministered

(

yyyy

-mm-

dd

)

(

hh:mm

)

(24

hour clock)Was Study Intervention started > 2 hours after Randomization? o Yes o No

If Yes, indicate the reason: o Pharmacy delay

o Patient NPO for surgery o Awaiting tube placement and/or verification Patient not available (procedure) Nurse not available Other (specify): ______________________________

Date and Time the last dose of study intervention administered

(yyyy-mm-dd) (hh:mm) (24 hour clock)

Initial Study Intervention Prescription grams/dayDid the prescription change during the study?

o

Yes o No

If Yes, record the new prescription

and the date/time of the change

grams/day

(

yyyy

-mm-

dd

)

(

hh:mm

)

(24

hour clock)

If the prescription changed again, record the new prescription

and the date/time of the change

grams/day

(

yyyy

-mm-

dd

)

(

hh:mm

)

(24

hour clock)

Timing of Study Intervention

Slide131

Record

each dose

of investigational product given

everyday

from

randomization

to

>

7

days post

last graft,

discharge, or 3 months from ACU admission,

whichever comes first

.

Prescribed # _______ gm/day

Daily Monitoring

Slide132

Record lab data

Daily

:

Study Days 1 – 14

Weekly

:

Study Days 15 – 90

Date (

yyyy

-mm-

dd

)

Creatinine, serum

(

highest)

T-

bilirubin

(highest

)

Urea

(highest)

PaO2/FiO2 (lowest)

Glucose

closest to 08:00

am

Ammonia (highest)

Albumin

(highest)

Lactate

(highest)

Platelets

(lowest)

WBC

(highest)

WBC

(lowest)

Highest or lowest as indicated

Glucose: closest to 8:00 A.M.

WBCs – if only one for the day record as both highest and lowest

Lactate from arterial blood draw

Daily/Weekly Laboratory Data

Slide133

Record

each burn

related operative procedure from ACU admission to 10

days

after the last graft, or stop of study intervention plus 3 days,

discharge, or 3 months from ACU admission,

whichever comes first

.

Date (

yyyy

-mm-

dd

)

 

 

 

 

Was the Operative procedure planned or unplanned?

o

Planned o Unplanned

o Planned o Unplanned o Planned

o Unplanned o Planned o Unplanned

o Planned o UnplannedType of Operative Procedure

(Select all that apply) 

Surgical excision (tangential or

fascial)

o

o

o

ooExtension and temporary covering (

xenograft

,

allograft and artificial skin)

o

o

o

o

o

Excision and

autograft

o

o

o

o

o

Delayed autograft

o

o

o

o

o

Excision and primary

closure/composite tissue transfer

o

o

o

o

o

Other (Please specify)

Burn Related Operative Procedure

Slide134

Record

only

the medications (or types of medications) listed here.

Daily from ACU admission to

10

days after the last graft, or stop of study intervention plus 3 days,

discharge, or 3 months from ACU admission, whichever comes first.

Do NOT record stool softeners

CONCOMITANT MEDICATIONS

Slide135

Record all Beta-Blockers given each day

CONCOMITANT

MEDICATIONS (cont.)

Slide136

Record

both the highest and the lowest heart rate.If only one heart rate is available,

record it as both

the highest and the lowest for that day.

This data is entered on the Concomitant Medication form

HEART RATE

Slide137

Report a Protocol Violation when

any of the following occur:

Investigational Product (IP) dose delivered is < 80% prescribed

over a 3 day average

.

Report

a dose related protocol violation when

both

of the following are

true

:

Dose received on the indicated day is < 80% prescribed

Dose received over a 3 day average is < 80% prescribed

Dispensing/dosing error of IP

Accidental

unblinding

Enrollment of a patient that does not fulfill inclusion/exclusion criteria

Open label glutamine given

Unapproved EN formula given

Other (specify)Protocol Violations

Slide138

Determine the percentage of IP received each day and indicate if a PV is being reported

Dose Related Protocol Violation (PV)

Slide139

Must be

entered into

REDCap

™

within 24 hrs

of becoming

aware

Enter up to 6 PVs per day by answering ‘Yes’ to the question ‘Another PV to add?’

Protocol Violations

Slide140

When all of you data is entered for a patient, click on the ‘Completed Data Entry’ button at the bottom left of the grid.

If the data is incomplete, an error message will pop up indicating what needs to be completed before moving the patient to the Queries stage.

Data Entry Completion

Slide141

Data Quality Management

Source Verification

Bench Mark Reporting

Data Quality Checks and Monitoring

Slide142

Simple and complex data query checks are implemented to ensure, complete, accurate, and consistent data is entered

Simple

Complex

Blank

field checks

Numeric ranges

Open text (manual DM checking)

Date Logic/Ranges (e.g. no dates in future)

Complex ranges – calculations (e.g. BMI)

Cross-form checks – consistency between forms (e.g. sex listed differently on demographics and SAE forms)

Required forms that are not done (e.g. protocol violation forms)

Blank forms

Data Query System

Slide143

Monitoring visits to conduct source verification and confirm study compliance with the protocol and regulatory processes will be conducted throughout the course of the study.

After a minimum of 2 patients have been enrolled at a site,

the central study team

will schedule a time

to conduct either an onsite

or

remote monitoring visit.

Visits may include review of:

Regulatory documents and binders

Source verification for specific enrolled subjects

Confirmation the study protocol is being followed

Training and delegation of authority logs

Monitoring

Slide144

The central study team will review recruitment reports monthly to identify and address slow enrollment and areas of concern

Recruitment Reports

Slide145

Data Quality reports will be generated every 4-6 months.

Each site with

>

10 finalized patients will receive an

individualized

site report.

Quality Reports

Slide146

Resources online

www.criticalcarenutrition.com

Slide147

www.criticalcarenutrition.com

From the CCN website, you can access:

CRS

REDCap

™

Study Tools

SPM; CRFs; Training Slides; Questionnaires; Logs

;

Forms

Critical Care Nutrition

Slide148

Potential Impact!

If the RE-ENERGIZE trial shows positive results, we can

immediately

implement this simple, inexpensive product around the world in both hospitals and ‘in the field’ settings. Thus, we will:

Save lives

Reduce infections

Shorten stays in hospital

Improve the physical recovery of burn injured victims

Save money

Slide149

Conclusions

RE-ENERGIZE trialWill ask a clinically important question

Has the potential to save lives and reduce morbidity whether positive or negative

Largest burn trial ever!

Results immediately translatable into practice

Thank you for your interest and support

Slide150