Transcript Slide 1

Study Procedures &
Operational Issues
Start-up Meeting
March 25, 2010
Kingston, ON
CERU Contacts
Sponsor
Dr. Daren Heyland
Cell: 613-484-5573
[email protected]
Project Leader
Janet Overvelde
613.549.6666 x6241
[email protected]
Data Manager
Jennifer Korol
613.549.6666 x6051
[email protected]
Role of Study Coordinator
Regulatory
Screening & Randomization
Pharmacy Communication
Blood Sample Draws
Data Collection
Monitoring Study
Intervention Administration
Monitoring & Identifying
SAEs
Protocol Violation Reporting
CANTREAT
Teamwork
Core Lab
Site Investigator
•Confirm patient
eligibility
•LPS Stimulation
•Blood Processing
•Infection adjudication
•SAE Reporting
•Shipping to central
lab in Ohio, USA
Research
Coordinator
Micro Lab
•Identify yeast
•Confirm presence of Candida
in qualifying respiratory
samples
•Sending respiratory
samples to OPHL
Pharmacy
•Checking treatment allocation
•IP preparation & dispensing
•Dose adjustments for renal
disease
•IP Accountability
Pre-Study Activities
Required Documentation
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REB Approval
REB Approved Consent
Fully-Executed Site Agreement
Team Qualifications
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Delegation of Authority
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CVs & Licenses
Overall
Pharmacy
Local Laboratory
Laboratory Accreditation & Reference Ranges
CRS Access Logs
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Study Coordinators
Pharmacy
Implementation
Manual pg. 9
Delegation of Authority
Must be kept up to date throughout
the duration of the study.
Implementation
Manual pg. 9
Training
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All study related training should be documented.
Any study related training initiated at the site
should be documented and a copy sent to
CERU PL
CRS Access Log
Implementation
Manual pg. 10
Screening &
Randomization
Inclusion
Criteria
Implementation
Manual pg. 14
Entering screening data
for a new patient:
Drop-down
Check boxes
Drop-down
Exclusion
Criteria
Implementation
Manual pg. 18
Eligibility Confirmation
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Should have documented confirmation from
MD regarding patient eligibility
Patient enrolled in CANTREAT study. Patient
randomized to the study at
hrs.
Patient met all the inclusion criteria and none of
the exclusion criteria.
Eligibility confirmed with Dr. ______________.
Consent obtained from _____________
(relationship to pt) on dd/mmm/yyyy at
hrs.
All questions & concerns addressed with SDM
at this time. Copy of consent given to SDM.
Date/time of entry: ____________
Signature of writer: ____________
Consent = NO
Indicate the reason why consent
was NOT obtained
Obtaining Informed Consent
Timing: When?
Consent must be obtained within 96 hrs of the
Candida +ve respiratory specimen sample time
Who obtains consent?
 Site Investigator or delegate i.e. sub investigator
or research nurse
 Must be specified on the Delegation of
Authority Log
Implementation
Manual pg. 21
Whom to Get Consent from?
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Patients are often incapable given acuity of
illness
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Substitute decision maker (SDM) or patient’s
legally acceptable representative
Explain the Study Procedures
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Explain VAP and treatment of identified
bacterial organism as standard of care
Presence of Candida “yeast” in the sputum,
usually NOT treated
Purpose of the study is to determine if treating
Candida, with antibiotics effective against
Candida, in addition to the usual antibiotics
administered for lung infections will improve the
outcome of these infections.
Explain Study Procedures
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Study Treatment:
GROUP 1: Standard ICU Care + antibiotic for
Candida
 GROUP 2: Standard ICU Care + Placebo (placebo
oral solution or a bag of salt water intravenously)
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Risks & benefits
Blood will be taken on days 1, 3, 8 & 14 to help
us understand how
Follow up at 90 days to check on patients status
If Consent Obtained, Remember to:
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Ensure SDM has signed and dated the ICF
Place original in study files, copy to medical
chart & copy to SDM
Write a note in the medical chart stating:
Name of SDM who provided consent, relation to
patient
 Date and time that consent was received
 Time that patient was randomized
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Telephone Consent
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Document in the medical chart that consent was
obtained via telephone before the patient was
randomized
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Follow up with the SDM to see that the ICF is
signed as soon as possible.
Consent Tools
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Consent template
ICF Essential Elements Checklist
Sample Medical Chart entry
Consent = YES
We are interested in knowing any
academic studies the patient is
co-enrolled in.
Study Procedures
Study Procedures
Manual
MD
Orders
STUDY BLOOD WORK
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Blood specimens should be drawn on the following days:
o Randomization day = study day 1, pre-treatment
o On study day 3
o On study day 8
o On study day 14 or last day of treatment, whichever comes first
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Each blood draw includes:
o 1 green top (sodium heparin) vacutainer
o 1 dark blue (trace element-free) top vacutainer
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Blood draws are to be coordinated with the research nurse.
STUDY DRUG ADMINISTRATION
Implementation
Manual pg. 26
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Administer once daily for 14 days
o If discharged to the ward before 14 days of study intervention received, study
drug administration should continue on the ward until 14 days received.
o If patient discharged from the hospital before 14 days of study intervention
received, study drug should be stopped on hospital discharge.
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Begin study drug administration intravenously. If the gastro-intestinal tract becomes
functional based on tolerance to feeds or diet, study drug will then be converted to
oral form. A separate order for conversion to oral will be written.
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If route of administration = intravenous:
o Administer study drug at the rate indicated on the product label.
o Study drug is compatible only with normal saline or D5W.
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If route of administration = oral:
o Administer 40 mL of investigational product via NG tube or orally.
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Dose Adjustments for patients with renal disease:
o Notify research Pharmacist or research coordinator if creatinine is outside the
normal range.
o Research Pharmacist to adjust study drug dosage as per protocol.
Study Intervention
Antifungal Therapy
(anidulafungin and fluconazole)
OR
Placebo
Study Intervention:
Active Treatment Arm
Products provided by Pfizer
Generic name: anidulafungin
Trade name: Eraxis™
IV administration
Generic name: fluconazole
Trade name: Diflucan
Oral administration
Study Intervention: Placebo arm
Normal saline OR D5W
IV Administration
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Infusion solution must be administered within
24 hours
Should be stored at room temperature
To be infused over 2-4 hours, as per pharmacy
instructions
Oral Administration
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Via NG tube or orally
Administer 40mL OD
Should be stored at room temperature
Duration of Study Treatment
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Administered once daily
Routes of administration: IV or PO
Total of 14 days
Continue if discharged to the ward
Exception: patients discharged from hospital
before 14 days of study treatment completed,
discharge day = last day of study treatment
Implementation
Manual pg. 27-29
Initiating Study Treatment
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Following randomization, notify the Pharmacy
Pharmacist will determine treatment code by
logging into CRS (UNBLINDED)
Pharmacy prepares study treatment
Administration of study treatment should start
within 2 hours of randomization
Things to consider once patient
starts to receive IP:
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Study Treatment Compliance
Presence of renal disease or changes in renal
function during the treatment period
Open-label antifungal use
Patient Randomized
IP initiated within 2 hours
IP administration initiated:
Anidulafungin (Eraxis)
OR Placebo
IP administered via IV
route minimum of 72 hrs
Speciation and susceptibility
results from OPHL, sent to
Pharmacy to adjust IP per
protocol
Compatible with normal
saline and DW5
“Active” treatment arm
will be switched to
fluconazole if organism is
susceptible
If patient switched to fluconazole following
If gastro-intestinal tract
switch to oral form, fluconazole loading
functional, can switch IP to dose should be IV route, then can proceed
oral route
with oral
Dose adjustments for renal disease.
SC reports any changes is renal
function to Pharmacy
Anidulafungin = NO changes required
Fluconazole = changes required
Open-label antifungals clinically
indicated, STOP IP & report
Protocol Violation
Last day of IP administration
is Study Day 14 (including
patients discharged to the
ward
Protocol Violations
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Used to report deviations in compliance with IP
Should be reported to CERU in “real time”
Blood Draws
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Type of samples
Sampling schedule
Local Lab Procedures
Central Lab
Implementation
Manual pg. 30
Sample Types
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Vacutainer tubes will be provided to the sites
Sampling Schedule
Lab Responsibilities
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Local
LPS Stimulation
Blood Processing
Storing Frozen samples
Shipping samples to
Central Lab in Ohio
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Central
Provide sites with LPS
stimulation media
Provide sites with
supplies
Provide sites with
shipping containers
Analyze samples received
from sites
Data Collection
More on Paper CRFs
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2-part NCR paper
Top copies of CRFs will be sent to CERU
Bottom copies to remain at the site
Study Days
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Study days defined according to the ICU flow
sheet:
Study Day 1 = Randomization Day
Study Day 2 = Next ICU flow sheet
Study Day 3 = Next ICU flow sheet
Study Day 4 = etc…
ICU flow sheet from 0700-0659
Implementation
Manual pg. 35
Source Documentation
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Health Canada requires study
Requireddocumentation
Documents
be retained for 25 years
Patient Folders
Worksheets &
other data
collection tools
Study Tools
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Patients Folders
Laminated reference cards
Worksheets
Patient ID List
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To be kept confidential
Enables identification of CANTREAT study
patiaents at the site
Required as per Health Canada and ICH GCP
Study Resources
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www.zapthevap.com
Project Leader