Download CRASH-2 Trial (1 gram of tranexamic acid/placebo) over 10 minutes

PRACTICAL ASPECTS
Topics
Getting the
trial started at
your hospital
How to send
your data
Maintaining
your Hospital
Site File
Patient
Information
& Consent
Emergency
Unblinding
Frequently
Asked
Questions
How to
randomise
a patient
Reporting
Adverse
Events
Good Clinical
Practice
Guidance
Trial Materials
Contacts &
further
information
Trial Treatment
How to give the
trial drugs
Introduction
• Your TRIAL SITE FILE contains all the
information and instructions you need for
conducting the trial – please use it
• If you have any questions about the trial
please contact the co-ordinating centre
staff
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Getting the trial started
Before the trial can start at your hospital
we must have the following documents:
• Ethics Approval (local and/or national)
• National regulatory approval (if required)
• Approval of your hospital (if required)
• A signed copy of the Principal Investigator’s
Statement
• A copy of our Hospital Information & CV Form
• A copy of the approved Patient Information Sheet
& Consent (if different from the protocol sent to
you)
(1)
Getting the trial started
Coordinating Centre is also part of your team:
o Good communication is essential
o Ask for help & advice if needed
o hare your successes and difficulties
Nominate someone to
be responsible in
your absence
Provide information and
training about the trial to
all members
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CREATE
A TRIAL
TEAM
(2)
Identify people to be
responsible for specific
trial process – they must
be interested in the trial
Every speciality
must be
represented:
• Nurses
•
•
•
•
•
•
•
•
•
Traumatologists
Intensivists
General Surgeons
Neurosurgeons
Orthopaedics
Clerical Staff
Pharmacy
Managers
Administrators
Consent
•
•
•
•
(1)
CRASH-2: involve patients who have
suffered serious injuries and are at risk of
life threatening haemorrhage
Most patients will have some impairment in
their level of consciousness caused either by
blood loss or coexisting head injury
Patients may not be able to provide written
informed consent
Trial treatment has to be administered as
soon as possible after injury
Consent
•
•
(2)
Need to comply with local approved
consent process
Should your Ethics Committee require
changes to the Patient Information Sheet,
please send a copy of the approved
version to us – this will be used to provide
you with copies in the patient treatment
packs.
Patient Information & Consent
• If written consent is required, please ensure
that all the original signed forms are kept in
the study Site File
• If you have told us that consent is legally
required, we will request confirmation that
consent has been obtained
• When requested, please send a copy of the
relevant section of your Randomisation Log
(found in your Site File)
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How to randomise a patient
(1)
There are two ways to randomise a patient:
Complete the entry form first to ensure the patient fulfils the
eligibility criteria. If the patient is suitable for the trial:
RANDOMISE BY TELEPHONE:
• Country and hospital must have access to the freecall service.
• Your Site File and Randomisation Posters will have the telephone number
you need to use – this number is unique to each country
• All the information on the Entry Form will be required by the operator
• The operator will give you the allocated treatment pack number
NON-TELEPHONE:
•After completing the Entry Form, select lowest numbered treatment pack.
•You must send the completed Entry Form to the co-ordinating centre as
soon as possible after randomisation
How to randomise a patient
(2)
All patients randomised or considered for
randomisation must be recorded in your Site File
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Trial treatment
Each treatment BOX has:
• a 4 digit unique number e.g. 4121
• 8 individual patients packs each numbered
with the box/pack number e.g. 4121/21
• Paper Entry Forms
• Paper Outcome Forms
• Patient Information Sheet/consent
Each treatment PACK has:
• 4 ampoules of tranexamic acid/placebo
• 100mL bag Sodium Chloride 0.9%
• 10 mL syringe
• needle
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How to give the trial drug
(1)
ALL AMPOULES ARE IDENTICAL AND CONTAIN 500mg OF
EITHER TRANEXAMIC ACID OR PLACEBO
LOADING DOSE - 2 ampoules over 10 minutes
Give immediately after randomisation
PRESCRIBE: “CRASH-2 Trial (1 gram of tranexamic acid/placebo) over 10 minutes”
• Using syringe provided in the treatment pack draw up 10 mL (2 ampoules of
tranexamic acid / placebo) and add to 100 ml bag of Sodium Chloride 0.9%
provided - Mix well
• Fill in date of randomisation on all 6 peelable labels on the cover of the pack
• Peel off a pre-printed INFUSION label and attach to bag
• If required, complete and attach a hospital infusion label to bag
• Connect infusion to patient’s IV line and infuse over 10 minutes
• Peel off a pre-printed DRUG CHART label, place at the front of prescription chart
• Peel off pre-printed randomisation labels and place one on PATIENT MEDICAL
RECORDS, one on ENTRY FORM and one on OUTCOME FORM
TXA solution for injection should not be mixed with blood for transfusion
or infusion solutions containing penicillin
How to give the trial drug
MAINTENANCE DOSE - 2 ampoules over 8 hours
Start immediately after completion of loading dose
PRESCRIBE: “CRASH-2 Trial (1 gram of tranexamic acid / placebo). Infuse at 60 L/hour”
• Draw up 10mL (2 ampoules of tranexamic acid / placebo) and add to 500mL bag of
Sodium Chloride 0.9% (to be provided by trial site)*
• Peel off a pre-printed INFUSION label and attach to bag
• If required, complete and attach a hospital infusion label to bag
• Connect infusion to patient’s IV line and infuse at 60mL/hour
• If infusion is terminated early for any reason, please record end time on prescription
chart
ENSURE PATIENT DETAILS ARE RECORDED ON
RANDOMISATION LOG IN THE SITE FILE
* Or other compatible solutions e.g dextrose 5% and Ringer’s solution
(2)
How to give the trial drug
INCOMPATIBILITIES
TXA solution for injection should not be mixed
with blood for transfusion or infusion solutions
containing penicillin.
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(3)
Data Collection
(1)
In your Site File you have 3 guidance sheets:
1.How to complete patient entry form
2.How to complete the outcome form
3.How to send your Entry and Outcome Data Forms
Please use these to help you send your data
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Data Collection
(2)
Internet: Primary data collection is to be done via the
‘collaborators’ intranet’ on our website
www.crash2.lshtm.ac.uk
A username and password to use this site will be sent to you by
email before you start the trial. If for any reason you do not
receive them, please email [email protected]
Email: data can also be submitted using the ‘electronic data
forms’. These forms can be found on a disk at the front of your
study site file. We can also email you these forms to you if
required.
These two are the preferred methods for sending your data as
they will eliminate data queries.
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Data Collection
(3)
If you are using fax to send forms it would be useful to attach a
treatment pack sticker on an outcome form ready for use as
soon as possible after randomisation. If a treatment pack
sticker is no longer available, please write the BOX/PACK
number in the box on the top right corner of the form.
Fax to +44 20 7299 4663
POST SHOULD BE USED ONLY AS A LAST RESORT: As there is a
delay in us receiving your data, this will disrupt your drug
supply. Please photocopy your data forms, keep the original in
your Site File and post the copy to:
CRASH TRIALS CO-ORDINATING CENTRE
London School of Hygiene & Tropical Medicine
Keppel Street, London WC1E 7HT
United Kingdom
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Emergency Unblinding
In general there should be no need to un-blind the allocated treatment.
If some contraindication to tranexamic acid develops after randomisation,
the trial treatment should simply be stopped.
Unblinding should be done only in those rare cases when the doctor believes
that clinical management depends importantly upon knowledge of whether
the patient received tranexamic acid or placebo (e.g. suspected
anaphylaxis).
In those few cases when urgent unblinding is considered necessary, the
randomisation service should be telephoned. The telephone number is in
your Site File. Please give your hospital name or ID code and the box/pack
number.
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Adverse Event Reporting
SERIOUS
NOT SERIOUS
Record in
medical notes
1.
Results in death
2.
Is life-threatening
3.
Requires hospitalisation or
4.
Prolongation of existing hospitalisation
5.
Results in persistent or significant disability or incapacity
6.
Is a congenital anomaly or birth defect
EXPECTED SIDE EFFECTS LISTED IN PROTOCOL (page 8)
DO NOT REQUIRE REPORTING (these are outcome data):
UNEXPECTED SIDE EFFECTS:
•
Death – unless believed to be directly due to the trial treatment
•
Pulmonary Embolism
1.
Complete a Serious Adverse Event
Form
•
Deep Vein thrombosis
2.
•
Stroke
•
Myocardial Infarction
•
Gastro Intestinal Bleeding
Telephone Randomisation Service
(phone number as per
Randomisation Poster or site file) to
register Serious Adverse Reaction;
give the information on the form
•
Multi-organ failure
3.
•
Result of trauma suffered by patient
Fax/email completed form to the Coordinating Centre within 24 hours
•
Medical events expected in severe injury
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Trial materials
BEFORE YOU START THE TRIAL YOU WILL
RECEIVE
• a site file compiled specifically for your
TREATMENT PACKS
• initially one box of 8 patient packs
hospital, containing contact details, further
information, guidance, spare forms and
space for completed data
• stock level is monitored by received
patient entries
• training CD with a PowerPoint presentation
• randomisation posters with step by step
instructions
PROTOCOLS
• protocol summaries and pocket cards
• we will send new packs when you reach
your minimum stock level which is dependent
on your randomisation rate
TRAINING AND PRESENTATIONS
Please contact the Co-ordinating Centre if
• you need more training materials for staff
sessions
• you are presenting the trial in meetings or
conferences
You will soon be able to order all trial materials via the COLLABORATORS’ INTRANET
on the trial website www.crash2.lshtm.ac.uk
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Site file
Investigator’s Master File to be maintained
(legal obligation)
• Screened patient – not randomised
• Randomisation List
• Original Signed Consent Forms (if required)
• Original Data
• All correspondence
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FAQs
Frequently asked questions and answers can be found
on the trial website & your site file
Please let us know of questions you get asked
frequently and we will add these to the website
Example of question:
Question: Is CRASH-2 a Head Injury Trial?
Answer: No – All adult trauma patients with ongoing haemorrhage OR at risk
of significant haemorrhage can be randomised. Patients with
concurrent head injury can be included.
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Good Clinical Practice
Good Clinical Practice (GCP): is an international ethical and scientific quality
standard for designing, conducting, recording and reporting trials that involve
the participation of human subjects.
Compliance with this standard provides public assurance that the rights, safety
and well-being of trial subjects are protected in accordance with the principles
that have their origin in the Declaration of Helsinki, and that the clinical trial
data are credible.
CRASH-2 WILL BE CONDUCTED IN ACCORDANCE WITH THE PRINCIPLES OF ICH-GCP
 The Principles of ICH-GCP and the Declaration of Helsinki can be found in your
Site File.
 Full versions can be found on our website
 Please be aware of your own country’s GCP Guidelines
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Contacts
Email addresses are formed like this: [email protected]
Ian Roberts
Clinical Co-ordinator
Donna Tooth
Assistant Co-ordinator
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Haleema Shakur
Trial Manager
Pablo Perel
Research Fellow
(Spanish Speaker)
Lin Barnetson
Data Manager
Maria Ramos
Administrator
Phil Edwards
Research Fellow
Tony Brady
Programmer