Transcript REDOXS© Trial Pilot - Critical Care Nutrition

©
The REDOXS Study
REducing Deaths due to OXidative Stress
The REDOXS© Study
REducing Deaths from OXidative Stress
Dietitian and Pharmacy Training
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a l C ar e
i als G
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Study Chair
Dr. Daren Heyland, MD, FRCPC
Project Leader
Rupinder Dhaliwal, BASc, RD
up C an
Administration of Study
Supplements
Duration of study supplements
Maximum 28 days
Minimum 5 days: In patients with ICU LOS < 5
days and get discharged to ward
Study Groups
GLN +AOX
Enteral
Supplement
Parenteral
Supplement
Glutamine + AOX
Dipeptiven +
Selenium
Placebo +
Selenium
Dipeptiven +
Placebo
Placebo +
Placebo
AOX
AOX only
GLN
Glutamine only
Placebo
SC blinded
Placebo
Pharmacist unblinded
Enteral Study Supplement
EN REDOXS © Formula
Parenteral Study Supplements
(Dipeptiven and Selenium)
+
US Product:
selenium
injection
SS Manual p 4-10
Study Supplements
• Pharmacist is unblinded
• Supplements to start ASAP
– within 24 hrs of admission to ICU
– within 2 hrs of randomization
• Duration: 28 days or death or ICU discharge
– min of 5 days IF transferred to ward, if not until ICU d/c
– Continuous infusion X 24 hrs but can be doubled up (12 hrs max)
Infusion of Supplements
• Parenteral supplements
–
–
–
–
–
as soon as patient resuscitated
10 ml/hr DEDICATED central port (eg. one of a triple lumen)
can run peripherally if needed (watch for phlebitis)
Do NOT infuse with medications
May piggyback with IV fluids, albumin, PN (no heparin/insulin)
• Enteral supplement
– NG tube OK or feeding tube
– 20 ml/hr, can be given via Y connector
– start regardless of whether MDs want to start enteral nutrition
nutrients vs.
nutrition
SS Manual p 10-16
• Minimize interruptions, make up volume
– Infuse at double rate for 12 hrs maximum on Day 1
• Intolerance to enteral feeding ( refer to feeding
protocol)
• Other enteral formulas, vitamins, minerals
• Renal Dysfunction
– Switch to lower protein formula
– Restrict fluid
– Refer to appendix
If received volumes < Prescribed = Protocol
Violation……….notify Methods Centre !!
Template of Study Orders
Study Supplement Manual Page 11
Imp. Manual: Tools
To optimize
delivery of
supplements
Study day 1=
ICU admission
until end of your
flowsheet
Enteral Nutrition
(EN)
ENTERAL REDOXS
formula
PARENTERAL
REDOXS formula (but
will be in a normal
saline type bag)
EN and ENTERAL REDOXS
being “Y”-ed in
Role of the Dietitian
Optimizing Enteral Nutrition
Canadian CPGs
www.criticalcarenutrition.com
Feeding Protocol
Glycemic Protocol
Elevate the Head of the Bed
Motility Agents
Small Bowel Feeding
RD manual p 13
SS Manual p 16
RD Manual p 5,6
Baseline Nutrition
Dietitian to collect:
• Prescribed kcal and
protein (baseline)
• Type of nutrition
support
• Start and stop date and
times
• Refer to Dietitian
Manual
Imp Manual p 29,30
RD Manual p 7,11
Daily Nutrition Data
Dietitian to collect
(for max 30 days):
•
•
•
•
Energy protein intake
Add propofol
Interruptions
Type of enteral formula
• + location of feeding tube
(daily data)
Collection in real
time essential !
Imp Manual p 37-39
Imp Manual: Tools
Dietitian Checklist
RD Manual: 19,20
Checklist is a tool…refer to webpage for data to be entered in eCRF
July 31st version
online
Propofol ≥ 6 hrs
Include in daily calories received as follows:
– If on EN only, add to EN calories
– If on PN only, add to PN calories
– If on EN + PN, add to PN calories
Do not add if not receiving EN or PN
Study Coordinator
Study Supplement Compliance
• Volumes must be
monitored DAILY in
real time by Study
Coordinator.
• If volumes <
prescribed, need to
report to CERU or
provide explanation and
take action to prevent
recurrence.
Protocol Violation
Protocol Deviation
Study Coordinator to ensure compliance
Dietitian to help
Imp Manual p 34
• Maximize EN nutrient and nutrition delivery
– use of feeding protocols
– small bowel feeding
• Minimize interruptions, make up volume
• Other enteral formulas with supplemental glutamine, vitamins,
minerals not allowed
– No supplements with high amounts of Zinc (5 mg max)
• Renal Dysfunction
– Switch to lower protein formula
– Restrict fluid
– Refer to appendix
Pilot study: Interruptions due to high urea only in
2% patient days (9% patients)
If received volumes < Prescribed = Protocol Violation……….Study
Coordinator to notify Methods Centre !!
RD Manual p 12-17
Case study: High GRVs
Mr. Smith who is 4 days post laporotomy (findings show
bowel is not compromised) has had high gastric residual
volumes > 500 mls for the last 48 hours. His enteral feeds
have been interrupted several times and are now on hold.
The MD in charge has also stopped the enteral study
supplements to give the gut a rest and he now wishes to
start parenteral nutrition.
What to do?
FAQs
• What if the prescribed calories and protein
changes over the 28 days of the study
duration?
• How do I get a prescribed calorie/protein
level if the dietitian has not assessed this?
Daily Monitoring
Dietitian
• Enteral Nutrition Adequacy
Study Coordinator
• Enteral Study Supplement Volumes
< 80 % prescribed: Protocol Violation Form
>= 80 and < 100 %: Provide explanation
• Parenteral Study Supplement Volumes
< 90% prescribed: Protocol Violation Form
>=90 and < 100%: provide explanation
SS Manual p 16
Pharmacy
Pharmacy Manual p 4
Pharmacy Web Access
To be completed by 2 of the most responsible pharmacists or
technicians
©
The REDOXS Study
REducing Deaths due to OXidative Stress
INSTITUTION:
INVESTIGATOR:
Pharmacy Web access Signature Log
SITE NUMBER:
Please complete the Electronic Data Capture (EDC) System Access Signature Sheet for the most responsible Pharmacist/technician(s) at your site
who will be checking the randomization or dispensing/checking study supplements. A signature and email address is required to create user
accounts for the web based system for the REDOXS© Study.
NAME
TITLE
SIGNATURE
EMAIL
DATE
NOTE:
By completing the information in the table above, the individual confirms they have been delegated the responsibility of checking the randomization
and dispensing/verifying study supplements for the REDOXS© Study.
The individual agrees to keep their password confidential to prevent unauthorized access to the data.
Reference: ICH GCP 5.5.3
Password can be shared by all pharmacy staff
Pharmacy Log In
Pharmacy Manual p 5
Pharmacy Manual p 6
Pharmacy Treatment assignment
Note: this is not the
randomization list
that will be used for
the study.
Supply of Supplements
• Fresenius Kabi: Dipeptiven, EN REDOXS
• Selenium: BIOSYN (EU), Baxter (Canada) or Pharmacy to
purchase on own* (US)
• Before start: Supplies to be shipped to sites once Ethics
approval received
• Need updated pharmacy contact and shipping address
*US sites: refer to Work Instruction for Selenium
Dispensing
Pharm Manual p 12
• ICU pharmacist  dispensing pharmacist
• Sign signature log
• Enteral supplements
– no mixing needed
• Parenteral supplements
– Mixing required: Dipeptiven (Glutamine) +
Selenium (AOX) + Normal Saline
If hypernatremia, can be mixed in
with D5W instead of saline!
Enteral Products
Pharm Manual p 12, 29
• Obtain appropriate enteral product
• Infuse at 20 ml/hour for all patients
• Generate pharmacy label (need 2 labels)
Pharm Manual p 12, 13
Remove company
label and staple to
Form B
Attach pharmacy
label to bottle
(maintain blinding)
Pharm Manual p 14
Enteral Dispensing Log
Pharm Manual p 15
Mixing of Parenteral Supplements
Dipeptiven (Glutamine) + Selenium (AOX) + Normal Saline
Final volume = 250 mls, hourly rate = 10 ml/hr
1. Determine dose of Glutamine according to Normal weight
•
Normal Weight (kg) = height (cms) –100 cms
•
Dose of Dipeptiven = Normal wt. X 2.5 mls
(This equals to Normal wt. X 0.35 gms of Glutamine or Normal
weight X 0.5 gms of L-alanyl-L-Glutamine)
2. Dose of Selenium = 12.5 ml (500 micrograms) = 1.25 vial
EU sites: dose is 10 mls (500 micrograms) = 1 vial
3. Combine the Glutamine + Selenium and remove this volume from
250 ml of normal saline
4. Replace normal saline with this mixture. Final volume =250 mls
Pharm Manual p 18, 32
Dosages according to height (PN)
If > 6 feet 5 inches (>196 cms)
•Final volume of parenteral solution will be between 250-300 mls
•Can still use 250 mls bag of saline
•If no normal saline to be used, use an empty sterile bag and add
supplements to the bag (instead of removing all normal saline)
•Final rate of solution will exceed 10 ml/hr
•Central line needed but peripheral may be used (72 hrs max)
Refer to
Revised
Worksheets
on web
Nov 2007
Pilot Study: no one > 190 cms (6’3”)
Parenteral Worksheet: GLN
Use
Revised
Worksheets
(for >196 cms)
on web
November 2007
Pharm Manual p 15, 31-41
Parenteral Worksheet: AOX
Use
Revised
Worksheets
(for >196 cms)
on web
November 2007
Parenteral Worksheet: AOX+GLN
Use
Revised
Worksheets
(for >196 cms)
on web
November 2007
Parenteral Worksheet: Placebo
Use
Revised
Worksheets
(for >196 cms)
on web
November 2007
Pharm Manual p 16, 42
Parenteral Label
Pharm Manual p 17
Parenteral Study Supplement Log
Pharm Manual p 10
Expiration of Supplements
• Selenium once opened: 24 hrs if refrigerated
• Dipeptiven once opened: mix immediately
• Once mixed, parenteral solutions have an
expiration of 96 hrs room temperature
– Can make in batches to last 3 days!!
Enteral Supplements once opened: 24 hrs
Pharm Manual p 19-25
Nutrient Accountability Logs
One log for each product except
for normal saline
Pharm Manual p 8,9
Monthly Site Inventory Log
Fax in to CERU monthly
US sites: Pharmacy stock vs. Baxter
Pharm Manual p 10, 11
Temperature Log
Fax similar log to CERU monthly
Delegation of Authority Log
Main pharmacist to sign this Delegation of Authority Log
Pharmacy Delegation Log
All pharmacy staff involved to sign
Case Study: Dosing error
REDOXS Pharmacist away for weekend and returns on
Monday and after reviewing logs realizes that Mr. J.S
accidentally received the wrong supplements. Should
have received GLN but received GLN+AOX instead for
the last 18 hours.
What to do?
1. Stop the infusion immediately
2. Inform research coordinator ASAP,
maintain blinding
3. Notify CERU immediately, Note to File
4. Steps to prevent recurrence
FAQs Pharmacy
• Keep vials of returned/destroyed products?
P. Manual page 16
• One password for all Pharmacists/technicians?
• Pharmacist or technician that dispenses the
supplements?
Questions??
Imp Manual Tools
REDOXS© Circular and Bulletin
Resources available
www.criticalcarenutrition.com >REDOXS