Transcript CLEAR III Clot Lysis: Evaluating Accelerated Resolution of

Pharmacist Training
Revised September 2010
AGENDA
 Overview
 Randomization
 Drug Supply
 Drug Shipment
 Drug Preparation
 Drug Accountability & Documentation
 Unblinding Procedure
OVERVIEW
 Multicenter, international, double-blind, randomized
study
 Approximately 500 patients will be enrolled across 75
study centers
 Primary objective- “define the long-term effects of
lysing ventricular blood clots with rt-PA on functional
outcomes
RANDOMIZATION
1:1
(maximum of 12 doses)
EVD = extraventricular drainage
EVD + rt-PA
1mg/ml every 8
hours (N=250)
EVD + PLACEBO
1ml every 8 hours
(N=250)
DRUG SUPPLY
 Recombinant tissue plasminogen activator (rt-PA),
Alteplase (Cathflo® Activase®) 2mg vials for
reconstitution
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Active drug
Packaged in boxes containing 6 vials/box
Manufactured by Genentech
Storage – refrigerated 2-8° C
Provided for the study
 0.9% Sodium Chloride for Injection, USP
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Placebo and Flushes
Use pharmacy supply- not provided
Alteplase (Cathflo® Activase®)
Drug Shipments – USA Sites
 Distributed to sites by the Investigational Drug Service
(IDS), Johns Hopkins Hospital (JHH)
 FedEx utilized as the courier
 Shipped in multi-purpose insulated shippers with
refrigerant packs
 Upon arrival, drug should be unpacked immediately,
examined, verified and placed in a refrigerator
 A signed copy of the invoice must be faxed to the
shipper
 Temperature monitoring devices are not used unless
requested
Drug Shipments - International
 Distributed to sites by the Investigational Drug Service
(IDS), Johns Hopkins Hospital (JHH) or Wellspring
Clinical Services
 Site will receive a “Notification of Shipment” e-mail
message
 Upon arrival, drug should be
 unpacked immediately
 examined
 checked against the enclosed document (Shipping Manifest)
 quarantined in a refrigerator
Drug Shipment (continued)
 The temperature monitoring device will be secured and
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directions will be provided for the return of the device
Complete the “Acknowledgement of Receipt” section on
the shipping document (Shipping Manifest) and return to
the shipper
Temperature data will be reviewed by Qualified Pharmacist
(QP)or Coordinating Center (CC)Pharmacist
QP or CC Pharmacist will approve the release the drug
from quarantine
Site will receive written documentation (Final Order
Release Certificate) regarding the release of the study drug
Drug Shipments (cont.)
 DRUG CANNOT BE USED until you receive
written documentation to release the drug
 Initial shipments will be sent when all regulatory
documentation has been received from the site
 Any concerns about the drug supply should be
reported to the shipper immediately
 To re-order drug
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Domestic -contact JHH IDS
International- process will be communicated depending upon
location
DRUG PREPARATION
(Active)
 Obtain study supply of Alteplase (Cathflo®Activase®)
 Utilizing aseptic technique, reconstitute* the vial with
2.2ml Sterile Water for Inj., USP
 Slight foaming is not unusual. Let the vial stand
undisturbed for several minutes to allow dissipation of
any large bubbles.
 DO NOT shake the vial.
*Based on product package insert for Cathflo® Activase®. Each vial contains 2.2mg of
Alteplase, which includes a 10% overfill
DRUG PREPARATION
 Final concentration is 1 mg/ml
 Draw up syringe(s) of 1 mg/ml Alteplase (Cathflo®
Activase®) into 3ml sterile syringes
 Cap the syringe with a sterile tip cap
 Label the syringe in a blinded fashion
 Expiration date for the syringe is 8 hours after
reconstitution if stored at 2-30°C
DRUG PREPARATION
(Placebo)
 Obtain a vial of 0.9% Sodium Chloride for Injection,
USP (preservative-free)
 Utilizing aseptic technique, draw up 1 ml into a 3 ml
sterile syringe
 Cap the syringe with a sterile rubber tip cap
 Label the syringe in a blinded fashion
 Expiration date for the syringe is 8 hours after
preparation (to match active drug syringe)
DRUG PREPARATION (cont.)
 Complete the drug accountability log
 Used Alteplase (Cathflo® Activase®) vials can be
discarded
 Expiration date for the syringe is 8 hours after
reconstitution/preparation if stored at 2-30°C
PREPARATION of FLUSHES
 Obtain a 10ml vial of 0.9% Sodium Chloride Injection,
preservative-free.
 Utilizing aseptic technique draw 4 ml of 0.9% Sodium
Chloride into a sterile 5ml syringe
 Cap the syringe with a sterile tip cap
 Label the syringe
 Expiration of syringe is 24 hours
Can I Freeze TPA?
 At time of preparation of subject’s dose, draw up the
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appropriate dose into a syringe
Cap syringe with a sterile tip cap
Label syringe
Store at -25° to -10°C
Discard frozen syringe(s) after 45 days*
Thaw syringe prior to dispensing
Re-label the drug for enrolled subject in a blinded
fashion
*Based on USP 797 Beyond Use Dating
DRUG ACCOUNTABILITY &
DOCUMENTATION
 Drug Accountability log
 Document receipt and disposition of drug
 Complete a log for Alteplase and placebo
 Running balance must be maintained
 Subject Specific log
 Document preparation for an individual subject
DRUG ACCOUNTABILITY
 Receipt and disposition of study drug is documented
on the drug accountability log
 Expired vials can be destroyed on site according to
your site specific policy for drug destruction
 Prior to destroying the study drug on site
 a copy of your site’s policy for drug disposal/destruction
must to sent to the Coordinating Center (CC)
Pharmacist
 a drug destruction form must be completed
Drug Accountability
 Document the destruction of the drug on the drug
accountability log
 Send a copy of the completed drug destruction form to
the CC Pharmacist
 Send a copy of the drug accountability log to the CC
Pharmacist
Drug Accountability Log
────────────────────────────────────────────────────────────────────
JHH- Investigational Drug Service
PAGE___OF___
Drug Accountability Record
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Principal Investigator:
IRB#
Title of Study: CLEAR III
“Clot Lysis:Evaluating Accelerated
Resolution of Intraventricular
Hemorrhage Phase III”
Drug Name, Strength, & Dosage Form:
L
i
n
e
Date
Patient's
Initials
Study #
Site:
Alteplase (Cathflo™ Activase®) 2mg/vial
(inventory unit = 1 vial) REFRIGERATE
Vial #
Quantity
Dispensed
or
Received
Balance
Forward
Lot Number
Your
Initials
______
#
1
.
2
.
3
.
4
.
5
.
20
Subject Specific Sheet
CLEAR PHASE III
Subject Name:
Investigator’s Name:
Subject #
Site #:
SUBJECT RANDOMIZED TO: ____________________________
Frequency schedule:
Every 8 Hours
(total 12 doses)
Date
Dose #
1
2
3
4
5
6
7
8
9
10
11
12
Time Removed from
Freezer
(if applicable)
Time of completion of
product
Pharmacist’s
Initials
CLEAR III – Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage Phase
RECORD OF DESTRUCTION OF INVESTIGATIONAL DRUG
Date Drug Destroyed:
Site Number:
Principal Investigator:
Investigator's Address:
____________________________
____________________________
____________________________
____________________________
Site name: ___________________________
Signature of person destroying the drug______________________________
DRUG NAME
Cathflo Activase
(Alteplase)
STRENGTH
2 mg vials
DOSAGE
NUMBER OF
FORM
VIALS
injection
Lot NUMBER
Unblinding Procedure
 Site investigator must contact the Study Chairman
 The Study Chairman will consult with the Medical
Safety Monitor
 Coordinating Center pharmacist or site pharmacist
will be contacted if unblinding is necessary
 Written request for unblinding will be required
PHARMACIST RESPONSIBILITIES
 Training requirement
 Adherence to study protocol
 All staff preparing compounded sterile products are
trained and competent (USP 797 Guidelines)
 All staff preparing study drug have been trained on
protocol procedures and drug preparation
 Appropriate documentation is maintained
 Storage and security of investigational drug
 Temperature monitoring
Communication
Contact the Coordinating Center Pharmacist (unblinded
pharmacist) to communicate:
 Any drug related concerns or occurrences
 Storage deviations
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Refrigerator malfunctions
Out of range temperatures
 Changes in pharmacy personnel listed in the
randomization system
 Contact information (shipping address, phone #, fax#,
e-mail addresses)
CLEAR III Website
 www.cleariii.com
 Pharmacy Manual
 Study Documents
 Current protocol version
 Pharmacist training presentation
REFERENCES
 CLEAR III website – www.cleariii.com
 Genentech- www.gene.com
 Alteplase (Cathflo® Activase®) product information -
www.gene.com/gene/products/information/cardiovascular/cathfloactivase/index
 USP* 797 Guidelines - www.usp.org
 Coordinating Center (phone) 410.614.6996
 JHH- Investigational Drug Service
 (phone) 410.955.6337 (fax) 410.614.8074
 Pager 410.283.2936
*USP – United States Pharmacopeia
CONTACT INFORMATION
Janet Mighty, R.Ph. MBA
(Coordinating Center Pharmacist)
Investigational Drug Service
The Johns Hopkins Hospital
600 N. Wolfe Street, Carnegie 180
Baltimore, MD 21287
Phone 410.955.6337, Fax 410.614.8074
E-mail: [email protected]