1. A Randomized Trial of Supplemental Parenteral Nutrition in
T P UP
A Randomized Trial of Supplemental Parenteral Nutrition in
Under and Over Weight Critically Ill Patients:
The TOP UP Trial
April 12th 2012
Study Sponsor: Dr. Daren Heyland
Project Leader: Rupinder Dhaliwal
Project Assistant: Roger Leung
Clinical Evaluation Research Unit
Baxter is NOT sponsor even though they have provided the product and some $ 1

2. Protocol: Version April 11th 2012

3. Background & Objectives

4. Point prevalence survey of nutrition practices in ICU’s around the world conducted Jan. 27, 2007
Enrolled 2772 patients from 158 ICU’s over 5 continents
Included ventilated adult patients who remained in ICU >72 hours

5. What study patients actually received?
Average Calories in all groups:
1034 kcals and 47 gm of protein
Result:
Average caloric deficit in Lean Pts:
7500kcal/10days
Average caloric deficit in Severely Obese:
12000kcal/10days 5

7. ICU patients are not all created equal…should we expect the impact of nutrition therapy to be the same across all patients? 7

8. TOP UP Trial: Hypothesis
Increased early energy and protein delivery with PN+EN to underweight (BMI < 25) and obese (BMI ≥ 35) critically ill patients will result in improved survival at 60 day versus standard EN alone 8 8

9. Objectives
Perform an initial multi-center pilot study in Canada,USA, France & Belgium in 160 patients to demonstrate feasibility
Assuming feasibility, large-scale 2000 patient multi-center, multinational trial will be undertaken 9 9

10. R Study Design Randomized Trial (unblinded) Primary Outcome
EN only
Primary Outcome
Stratified by:
Site
BMI
Med vs Surg
On EN
ICU patients R
BMI <25
60-day mortality
BMI >35
Fed enterally
EN plus supplemental PN for 7 days

11. Objectives: Pilot Study
Primary Aim:
Difference in the calories and protein received between the control and intervention groups
Estimate recruitment rate
Evaluate the safety, tolerance, and logistics around providing supplemental PN in the study population, e.g.
To ensure adequate glycemic control in both groups
To ensure other metabolic consequences of the feeding strategies are minimized
To establish adequate compliance with study protocols and completion of case report forms.
Secondary Aims:
Explore the effect of differential intake of protein/energy on muscle mass and muscle function.

12. Outcomes: Pilot study Primary outcome: 60 day mortality
Secondary outcomes:
ICU (28 day) mortality
Hospital mortality
Duration of mechanical ventilation
Duration of stay (ICU and hospital)
Development of ICU-acquired infections
Multiple organ dysfunction (SOFA and PODS)
Functional status, HR QOL at 3 & 6 months
Muscle Function Tests

13. Study Overview
Imp Manual p 9

14. Pilot Study: Participating Sites
Target: 160 patients from 8 institutions
Royal Alexandra Hospital, Edmonton (Jim Kutsogiannis)
University of Alberta Hospital, Edmonton (Dean Karvellas)
University of Colorado, US (Paul Wischmeyer )
Erasme University Hospital, Brussels (Jean Charles Preiser)
Hôpitaux Universitaires, Strasbourg, France (Michael Hasselmann)
Grey Nun’s Hospital, Edmonton (Dan Stollery)
University of Wisconsin (Ken Kudsk)
Oregon Health Sciences University (Robert Martindale)
Will add Grey Nun’s to next version of the protocol

15. TOP UP Teamwork Site Investigator Nurse Pharmacist Dietitian
Regulatory
Inclusion/exclusion criteria
ICU infection adjudication
SAE reporting
Nurse
Adjust EN + PN hourly
Product Reconstitution?
Pharmacist
Checking allocation
Dispensing
Logs
Dietitian
Dosing Calculation
Optimizing nutrition
Monitoring Adequacy
Study Coordinator
Regulatory
Screening/Randomization
Pharmacy communication
Data collection
Study intervention monitoring
Collaboration with SI
SAE reporting
Protocol Violation reporting

16. Role of Site Investigator
Delegation of Authority
Patient Eligibility ICU Infection adjudication SAE identification/assessment
Investigator Confirmation
As per, ICH, GCP, each Site Investigator MUST be responsible for the overall conduct of the study at their site.
Here are a few specific tasks related to the TOP UP Study
Patient Eligibility already discussed

17. Delegation of Authority Logs
Imp Manual p 11,12
“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)”
Completed Log to be sent to CERU before start of trial
Site Investigator needs to include names of:
all sub investigators, Co investigators,
Research Coordinators
Dietitian
Other staff involved in the study

18. Imp Manual p 13, CRFs
Inclusion Criteria
1) Mechanically ventilated adult patients (≥18 years old) 2) Expected to remain mechanically ventilated for more than 48 hours 3) On enteral nutrition or expected to initiate enteral nutrition within 7 days from ICU admission 4) BMI < 25 or >35 based on pre-ICU actual or estimated dry weight
Discussion Points:
Inclusion criteria: assessment made at the time of screening
What if the criteria #1, 2 or 3 change from screening to the time of randomization?
#3. inclusion criteria: what if pt on EN before ICU admission?
We say this is OK as long as they have not reached goal rate…….need to specify goal rate as >60%? Come back to this on Exclusion slide
If using estimated weight/height, you may add a buffer of  1 for BMI after rounding

19. Imp Manual p 14, CRFs
Exclusion Criteria
>72 hours from admission to ICU to time of consent (your ICU)
Not expected to survive an additional 48 hours from screening evaluation
Lack of commitment to full, aggressive care (anticipated withholding or withdrawing treatments in the first week but isolated DNR acceptable)
Patients already receiving PN on admission to ICU (does NOT refer to those that received PN in hospital prior to this acute episode of illness)
Discussion Points:
Text in red indicates changes/clarification made as a result of Feb meeting

20. Exclusion Criteria 6. Pregnant or lactating patients
Imp Manual p 14, CRFs
Patients with diabetic ketoacidosis or non ketotic hyperosmolar coma
6. Pregnant or lactating patients
Patients with clinical fulminant hepatic failure (see definition)
Patients with Cirrhosis Child’s Class C Liver Disease (except those on a transplant list or transplantable)
Dedicated port of central line not available
Known allergy to study nutrients (soy, egg or olive products)
Enrolment in another industry sponsored ICU intervention study (co- enrollment in academic studies will be considered on a case by case basis)

21. Eligibility confirmation
Document in the medical chart or
Sign worksheet by MD and keep as source
Prompted at time of Pre randomization
Refer to Consent Training Slides

22. Infection Adjudication Site Investigator to make determination of a newly acquired infection based on antibiotic and microbiology data

23. Infection Adjudication
CRS/REDCAP manual p 21-27
For EVERY suspicion of infection that gets triggered by the earlier asked questions, the Site Investigator (MD) MUST determine the following
Is IT a newly acquired infection? If so, determine:
Category
Degree of Certainty
If NOT, determine:
If PREVIOUSLY ADJUDICATED INFECTION, link to the earlier suspicion #.
To be done by collaborating with R Coordinator and Medical Chart:

24. Suspicion of ICU Infection: Antibiotics
CRFs p 40, 41
Is this antibiotic prescribed for prophylaxis?
Is this a substitute for an antibiotic previously ordered for an infection that occurred within 72 hrs of admission to ICU?
NO to both
YES to either
IF the antibiotic is started started > 72 hrs ICU admission, then you will need to answer these 2 questions
Clinical Suspicion of Infection
Need adjudication by
Site Investigator/MD Delegate
No adjudication needed

25. Suspicion of ICU Infection: Microbiology
CRFs p 42, 43
Is this organism a manifestation of an infection that occurred within the first 72 hrs of admission? NO
YES
Clinical Suspicion of Infection
Need adjudication by
Site Investigator/MD Delegate
Indicate if:
Relapse/Recurrent OR
Persistent infection
No adjudication needed

26. Infection Adjudication: REDCAP
CRS/REDCAP Manual p 24
Infection Adjudication: REDCAP
This is a newly acquired infection
This is NOT a newly acquired infection
This is a previously adjudicated infection

27. Infection Adjudication
Site Investigator will need:
Access to view the Infection Adjudication table on REDCAP (Research Coordinator to show this)
Appendix 9 Categories of Infection
Appendix 10 Definitions of No Newly Acquired Infection
Medical Chart
Refer to CRS/REDCAP Manual pages for step by step process

28. SAE Identification and Reporting

29. Adverse Event must be serious and unexpected to be reported
Imp Manual p XX-XX
SAE Identification
A serious adverse event is any untoward medical occurrence that at any dose,
Results in death
Is life threatening (the subject was at immediate risk of death from the event
Results in persistent or significant disability/incapacity
Requires in patient hospitalization possibly related to the use of the study materials
Prolongs of hospitalization.
Is a congenital anomaly or birth defect
Is an important medical event that may jeopardize the patient and may require medical or surgical intervention to prevent one of the outcomes listed above medically important condition
An unexpected adverse event is that event that is NOT expected due to the progression of the underlying disease or co-morbid illnesses.
Adverse Event must be serious and unexpected to be reported

30. SAE Reporting (to CERU)
Imp Manual p X
EVENT must be SERIOUS AND UNEXEPECTED TO BE REPORTED
Must be done on electronic data capture system and faxed to CERU

31. Imp Manual p XX-XX

32. Imp Manual p XX-XX

33. Imp Manual p XX

34. Imp Manual appendix J

35. SAE Reporting to Regulatory Bodies
If SAE is related, CERU will report to Regulatory bodies, Sites and Baxter within 7 days (fatal) or 15 days (non fatal)
NEED TO ASK:
WHAT THEIR REG AGENCY IS…..BPharm?
ANY ADDITIONAL SAE REPORTING REQUIREMENTS ARE?
I THINK THIS REPORTING SHOULD JIVE WITH THEIR NEEDS BUT NEED TO CHECK (BASED ON REDOXS)

36. Investigator Confirmation
CRS/REDCAP Manual p 30

37. Study Groups Name of Group Intervention Supplemental PN
Imp Manual p X
Study Groups
Name of Group
Intervention
Supplemental PN
EN (enteral nutrition) plus Olimel
EN only EN

38. To be determined by the dietitian/MD
Dosing Procedures
(both groups)
Dosing of the intervention will depend upon the energy and protein needs of the patient
To be determined by the dietitian/MD

39. Protein and Calorie needs
Protocol, Imp Manual p X
Guidelines for Dosing of Protein and Energy Based on BMI
Upon enrolment, the dietitian/MD will:
Calculate prescribed energy and protein intake as per standard practice
2. Ensure that minimum energy and protein needs are met as follows
Minimum Energy
Minimum Protein
BMI<25
25 kcals/kg actual wt
1.2 g/kg actual wt
BMI ≥ 35
20 kcals/kg ABW*
1.2 g/kg Obesity-ABW*
CHANGE INSTRUCSTIONS IN THE IMP MANUAL, page 34: replace RANDOMIZATION with ICU ADMISSION
*Obesity-adjusted Body weight= IBW + [actual weight – IBW] x 0.25, where IBW is ideal body weight (BMI of 25)

40. Must be done asap after randomization
Imp Manual p X
Prescribed Volume
3. Determine the prescribed volume for EN (or study PN, or EN + study
PN) in mls/24 hrs to meet the prescribed energy and protein needs
MUST use enteral formula of 1.2  0.2 kcal/ml
Meet protein needs over energy needs
4. Determine the hourly rate of EN (or study PN, or EN + study PN)
(assume PN = 1 Kcal/ml)
Must be done asap after randomization

41. Study Tools

42. Other considerations…Propofol
Propofol calories to be factored into assessment of caloric needs, only as per discretion of dietitian/MD

43. Enteral Nutrition (both groups)
Imp Manual p X
Enteral Nutrition to start as per usual practice (patient stabilized, NG/Feeding tube in place)
Standard enteral nutrition formula 1.0 to 1.4 kcals/ml
(hypercaloric formulas not allowed)
NO protein supplements (for 7 days)
NO probiotics (for 7 days)
NO glutamine supplements (for 7 days)
Start at 25 ml/hr and increase every 4 hrs as tolerated until goal rate
Discontinue when the feeding tube comes out
Refer to Enteral Nutrition Algorithm & Paired Feeding Algorithm appendices C & F

44. Trace Elements and Multivitamins
Imp Manual p X
DO NOT add to the PN solution
If patient does not receive EN and is dependant on PN for >48 hrs,
IV supplementation is recommended
Suggested guidelines
Standard doses of multivitamins
5 mg zinc
1 mg copper
0.5 mg manganese
10 mg chromium
60mcg selenium.
use commercially available trace element solutions
doses can be adjusted at discretion of the medical team
Daren…use of “open label supplements” still applies at end of study period, no?

45. Dietitian Determine Energy/protein needs (prescribed Volume)
Follow Canadian Clinical Practice Guidelines Assist with data collection
Baseline Nutrition Assessment
Daily EN monitoring
Daily PN monitoring (non study PN)

46. Baseline Nutrition
CRFs p 12-13

47. CRFs p 20-21,23
Daily EN Monitoring

48. Daily PN Monitoring (non study PN)
CRFs p 22, 24
Daily PN Monitoring (non study PN)

49. Study Days and Data Collection
CRFs p 3
Study Days and Data Collection
Data MUST be collected according to calendar day as described below
Do NOT collect data according to your flow sheet unless it runs from
00:00 to 23:59 (midnight to midnight)

50. Supplemental PN group

51. Olimel N9E (5.7%)
Imp Manual p XX, XX
Amino acids
3-in-1 PN solution that contains glucose, lipid emulsion and an amino acids
Blend of desirable lipids: olive oil, soybean oil (ratio 80/20)
Alpha-tocopherol/moderate PUFA,
better vitamin E status
less lipid peroxidation.
Protein and energy content of Olimel N9E enables the maintenance of an adequate nitrogen/energy balance
1 Litre bags, provided by Baxter
Dextrose
Lipid emulsion
Spike insertion site

52. Olimel N9E (with electrolytes)
Product monograph

53. When to start Olimel? Start as soon as central line access
Imp Manual p X
When to start Olimel?
Start as soon as central line access
Preferably within 2 hrs of randomization

54. Paired Feeding
Imp Manual p XX-XX
Enteral and parenteral solutions provided continuously over 24 h
Rate of PN depends upon rate of EN
Adjust PN hourly so that EN + PN = target rate as determined by dietitian/MD
Initiate PN study solution at 25 ml/hr (or faster) and advance by 25 ml q 4 hrs to target rate as tolerated
Monitor blood sugars and electrolytes every 4 hrs as needed
Do not advance PN/EN if BS, K, Phosp, Mag becoming more abnormal (ranges as per your local site) .
To reach the target combined rate by EN plus PN within 24 hrs from randomization

55. Imp Manual appendix F

56. Sample MD orders (Supplemental Group)
Imp Manual p X

57. Duration of Study Intervention
Imp Manual p X
ICU admission
7 days post randomization (means day of randomization PLUS 7 full days)
Study Intervention
Randomization
Consent to be obtained within 72 hrs from ICU admit

58. Before or at 7 days: Supplemental Group
Imp Manual p X
Duration of intervention = ICU admission to 7 days post randomization (=day of randomization PLUS 7 full days)
ICU admit
7 days post randomization
If d/c from ICU to ward prior to 7 days
If in ICU & PN indicated, use Olimel
If out of ICU & PN indicated, use standard PN
Daren……….I think that this can be deleted or needs to be changed because:
we are not saying use open label Olimel
we are saying if d/c from ICU, use standard PN
Don’t thin we will be asking to follow calorie assessment on floor if using standard PN
I will need direction on how to address this too in the protocol and Imp Manual
Continue study PN until:
50 % goal rate until day 7 OR
until patient tolerating adequate
po intake, whatever happens first
NO daily titration needed

59. Use of Non Study Parenteral Nutrition
Imp Manual p X
Use of Non Study Parenteral Nutrition
If parenteral nutrition is truly indicated
In ICU: use Olimel until study day 28 maximum
When on floor after ICU: use standard PN
Daren………….this was what we had decided in Edmonton. Please check wrt slide # 32
Both groups:
If non study PN received
before 7 days
PROTOCOL VIOLATION
Report to CERU asap 59

60. EN only group

61. Refer to Enteral Nutrition Algorithm
Imp Manual p X
Enteral Nutrition to start as per usual practice (patient stabilized and NG/Feeding tube in place)
Standard enteral nutrition formula
1.0 to 1.4 kcals/ml
(hypercaloric formulas not allowed)
NO protein supplements (for 7 days)
NO probiotics (for 7 days)
NO glutamine supplements (for 7 days)
Start at 25 ml/hr (or and increased every 4 hrs as tolerated until goal rate
Discontinue when the feeding tube comes out
Refer to Enteral Nutrition Algorithm

62. Imp Manual appendix C

63. Sample MD orders (EN only Group)
Imp Manual p X

64. Before or at 7 days: EN only group
Imp Manual p X
Duration of intervention = ICU admission to 7 days post randomization (= day of randomization PLUS 7 full days)
ICU admit
7 days post randomization
If within 7 days, PN is clinically indicated and still in ICU,
Use Olimel
If Olimel or any PN is received before 7 days, this is considered a Protocol Violation and must be reported to CERU!
If after 7 days,
PN is clinically indicated and still in ICU use Olimel
If out of ICU & PN indicated, use standard PN
Daren……….I think that this can be deleted or needs to be changed because:
we are not saying use open label Olimel
we are saying if d/c from ICU, use standard PN
Don’t thin we will be asking to follow calorie assessment on floor if using standard PN
I will need direction on how to address this too in the protocol and Imp Manual

65. EN only & Supplemental PN group
Both groups
EN only &
Supplemental PN group

66. Trace Elements and Multivitamins
Imp Manual p X
DO NOT add to the PN solution
If patient does not receive EN and is dependant on PN for >48 hrs,
IV supplementation is recommended
Suggested guidelines
Standard doses of multivitamins
5 mg zinc
1 mg copper
0.5 mg manganese
10 mg chromium
60mcg selenium.
use commercially available trace element solutions
doses can be adjusted at discretion of the medical team
Daren…use of “open label supplements” still applies at end of study period, no?

67. Co-interventions Follow Canadian Nutrition Guidelines
Imp Manual p X
Follow Canadian Nutrition Guidelines
Glycemic Control Protocol
Daily sedation vacations
Sepsis management guidelines
Daily trials of weaning from mechanical ventilation
EU guidelines vs. Canadian…………..do we mention this in the protocol?

68. Investigational Product
Dispensing & Storage

69. Pharmacy
For most sites, the pharmacy may only be involved in the initial receipt of the Olimel.
The Research Coordinator/delegate will therefore be responsible for the following:
storage of Olimel
dispensing of Olimel (including addition of labels)
completion of dispensing and accountability logs
sending temp logs to CERU monthly
maintenance of inventory and destruction of the expired/unused product

70. Olimel N9E
Imp Manual p X
Will be supplied to all sites before enrollment starts At time of delivery, if pre-activation occurs (solution has turned milky) do not use and report to CERU Project Leader Unmixed product: store between 15 to 30 degrees C. Do not freeze.
Dedicated Central line needed,
piggybacking with other lines not recommended unless standard practice for PN at your site

71. Central Randomization System
CRS/REDCAP Manual p 12
Central Randomization System
Upon randomization, Research Coordinator will be notified of the study group
the patient has been randomized to
EN only or
EN + Supplemental PN

72. Supplemental PN For day 1:
Imp Manual p X
For day 1:
Research Coordinator to obtain hourly rate of infusion from dietitian/MD
Prepare enough 1 litre bags of the
investigational product to last one day
Example: Dietitian/MD has determined that the hourly rate is 65 ml/hr:
the total volume needed for 1 day would be 65 X 24 = 1536 mls.
The pharmacist /delegate is to prepare 2 X 1 Litre bags of the product.
In order to prevent running out of product before the bag
change time, you may need to send 2 X 1 litre bags on day 1
Pharmacy to prepare the parenteral solution according to group
Add dextrose to meet minimum calorie and protein needs
Add trace elements, vitamins as per protocol
Send to ICU within 4 hrs of randomization
Attach a blinded label on packages
Complete dispensing logs (pending)

73. Supplemental PN For Subsequent days:
The Research Coordinator to determine how much enteral nutrition the patient is anticipated to tolerate and will prepare enough Olimel accordingly.
Example:
1. Goal rate = 65 ml/hr
2. Patient tolerating 25 ml/hr well today (or expected to)
3. Prepare enough product for remaining volume = 40 ml/hr X 24 = 960 mls = 1 X 1 litre bag

74. Olimel in overpouch
To open the Olimel, remove the protective overpouch.

75. Labels Unblinded labels Appx 3” x 5” size
Imp Manual p X
Study: The TOP-UP Study
ID #: NCT
Olimel N9E
PARENTERAL USE ONLY
Canadian Sponsor: Dr. Daren Heyland
Clinical Evaluation Research Unit, Kingston General Hospital,
76 Stuart St, Kingston, ON K7L 2V7
Randomization #: _________
Patient ID: ________________
Patient Name: _____________
Directions: Run at maximum goal rate of XX ml/hr and titrate down as enteral feeds increase.
Storage: Room temperature
Expiration: 24 hrs
Unblinded labels
Appx 3” x 5” size
Generate and attach 1 label for outside of reconstituted bag
Labels must be placed on extra bags needed for after hours (expiration date and time must be recorded…..by RN)

76. Imp Manual appendix D

77. Imp Manual appendix E

78. Imp Manual p X
Nursing Procedures
Training Slides available on Reconstitution of Olimel
nutrition.com

79. Reconstitution of Olimel
done by Nurse and/or Research Coordinator

80. Olimel in overpouch
To open the Olimel, remove the protective overpouch.

81. After removing pouch, check the Oxygen indicator
Black
Light yellow brown
After overwrap has been removed, Olimel can be stored for 24 hours under
refrigeration followed by 24 hours administration

82. Check non permanent seals
Confirm the integrity of the bag and of the non-permanent seals
Use only if the bag is
not damaged, if the non-permanent seals are intact (i.e. no mixture of
the contents of the three compartments)
if the amino acids solution and the glucose solution are clear, colourless
practically free of visible particles, and
if the lipid emulsion is a homogeneous liquid with a milky appearance

83. 1. Ensure that the product is at room temperature when breaking the non- permanent seals 2. After removing overpouch, manually roll bag from hanger side down
Manually roll the bag onto itself, starting at the top of the bag (hanger end). The non-permanent seals will disappear from the side near the inlets. Continue to roll until the seals are open along approximately half of their length.

84. Continue rolling the bag until all non permanent seals are broken ½ way

85. Solution turns milky showing that the seals are broken (1/2 way)

86. Mix by inverting the bag at least 3 times

87. Mix well by inverting the bag 3 times
Mix by inverting the bag at least 3 times

88. Solution will turn to a milky color & is ready to hang
Use immediately after reconstitution
After reconstitution, the mixture is a homogeneous emulsion with a milky appearance.

89. Overview of steps and timelines
Screen patient
Eligible patient
(checked by MD)
Research Coordinator obtains consent
Randomizes patient on CRS
Dietitian determines dosing of calories and protein
Writes sample entry Note in chart
Facilitates Medical Orders in chart
72 hrs + 2 hrs from admission
Pharmacist m ay be replaced by Research Coordinator
Research Coordinator/Pharmacist dispenses product for patient
Research Coordinator informs RN
Patient started on intervention

90. Muscle Function Tests

91. Volunteer U/S training records must be submitted to CERU
Imp Manual p X, CRFs 32-33
Weekly U/Sounds
Why?
To assess Muscle Layer Thickness (MLT) of the M.
vastus intermedius and M. rectus femoris
When?
Weekly PLUS within 72 hrs of CT Scan
Whom?
To be done by site investigator or designated clinician (RN specialist, R Coordinator, RN, fellow)
How?
Refer to Ultrasound Procedure pages in Imp Manual
Volunteer U/S training records must be submitted to CERU

92. Abdominal/Pelvic CT Scan
CRF p 34-35
Why?
Assess muscle mass (at 3rd lumbar vertebrae) as a predictor of
lean tissue mass
When?
CT Scans done 1-2 days prior or after ICU admission and all
subsequent scans
Whom?
Research Coordinator to retrieve scans of previously done CTs and
obtain copies and send DE-IDENTIFIED to University of Waterloo
How?
CT Images already performed for clinical reasons
Not to be done for the study if not clinically indicated
Mourtzakis M et al Critical Care Canada Forum, 2009.

93. Hand Grip Strength Why? When? Whom? How?
Imp Manual p X
Why?
To assess the physical strength
When?
ICU and hospital discharge
Whom?
To be done by the Research Coordinator
How?
On a patient that is awake and attentive, upright with elbow at 90 degrees
Using a hand dynamometer (Jamar) on dominant hand, three readings (sustained 5 sec, rest for 15 sec between)
REFER TO HAND GRIP STRENGTH TEST MODULE (SLIDES)

94. 6 Minute Walk Test Why? When? Whom? How?
Imp Manual p X
Why?
One time measure of functional status of patients
When?
Prior to hospital discharge
Whom?
To be done by the Research Coordinator
How?
Calculate the total distance walked by patient in 6 minutes.
On a patient that is able to walk, need a long corridor (30 metres)
Patients with recent unstable angina are excluded
Ensure that the patient is safe, chair nearby
Worksheets, specific instructions, script provided

95. Need to get from physio, RN flowsheet or RN (daily)
CRF page 36,37
Rehab Practices
Need to get from physio, RN flowsheet or RN (daily)

96. Research Coordinator Procedures
Imp Manual
Research Coordinator Procedures
Consent (Training Module)
Training of nurses
Data Collection
Protocol Violations

97. Case Report Forms
CRFs April 12th 2012

98. Duration of Data Collection

99. The duration of daily data collection and frequency will vary depending upon each data element/form and is as follows:
· Collected once:
Baseline Barthel ADL Index, Baseline SF-36, Nutritional Assessment, Baseline, Nutrition Timing, Ventilation/Dialysis, Outcomes Barthel ADL Index, Muscle Function Testing (6-min Walk Test & Hand Grip Strength Test only), Hospitalization Overview, 3-month SF-36 Follow-up and 6-month SF-36 Follow-up
· Daily from Study Day 1 until ICU discharge or death for a maximum of 28 days from ICU admission:
Daily Nutrition Monitoring, Daily Organ Dysfunction, Daily Laboratory and Intra Abdominal Pressure, Rehabilitation Practices and Concomitant Medications
· Daily from Study Day 1 until 3 days after ICU discharge or death for a maximum of 28 days:
Antibiotic/Antiviral/Antifungal and Microbiology
· Weekly/Other specified intervals:
Muscle Function Testing (Weekly study Femoral Ultrasounds) and
Abdominal/Pelvis CT Scans/Femoral Ultrasounds 

100. Duration of Study Intervention

101. *7 Days post randomization = Day of randomization Plus 7 full days
The duration of the study intervention is:
7 days post randomization* or until death whichever comes first
Exceptions: If the patient is discharged from the ICU to your hospital ward before 7 days:
Supplemental PN Group: Continue PN intervention until day 7 post randomization* or until the patient is tolerating adequate amounts of oral nutrition (i.e. > 50% caloric goal orally)
Both groups: Collect daily data from Study Day 1 until 7 days post randomization*
Both groups: Collect antibiotic and microbiology data from Study Day 1 until 10 days post randomization** 
*7 Days post randomization = Day of randomization Plus 7 full days
**10 Days post randomization = Day of randomization Plus 10 full days
EXAMPLE:
Study Day 1 = Patient admitted to ICU
Aug 23:20
Study Day 2 = Patient randomized to TOP-UP
Aug 12:35
Study Day 8 = Patient discharged from ICU
Sept 18:04
Study Day 9 = Last day of Daily Data Collection (7 days post randomization*)
Sep 23:59
Study Day 12 = Last day of Antibiotic and Microbiology collection (10 days post randomization**)
Sep 23:59

102. CRS/REDCAP Manual April 11th 2012

103. Resources online