Download Department of Diabetes and Vascular Medicine

Exeter Clinical and Health Research
Standard Operating Procedure: TriMaster Study Screening Visit
SOP Number:
NIHRexe /232/TriMaster
Effective Date: 16/01/2017
Version Number & Date: V2.1 03/04/2017
Reviewed: 03/04/2017
Review Date: 01/04/2019
Superseded Version Number & Date: V1 27/09/2016
Author:
Name: Kim Rowden
Position: Senior Research Nurse
Signature: ……
Date: 03/04/2017……………………..
Approved by:
Name: Catherine Angwin
Position: Research Project Manager
03/04/2017
Signature: …………………………………………. Date: ……………………………………..
Senior Management Agreement:
Name: Gillian Baker
Role: CRF Manager
03/04/2017
Signature: ……………………………………………. Date: …………………………………...
I agree that appropriate members of my workforce (as named above) have written and approved
this SOP for use in clinical research.
Page 1 of 10
SOP Number: NIHRexe/232 TriMaster
Effective Date: 03/04/2017
Version: 2.1
1. BACKGROUND:
TriMASTER is a MRC-funded study aiming to develop a stratified approach in Type 2 diabetes
that will result in more effective use of glucose lowering therapy.
In this study the research team aims to identify subgroups of patients that respond well or poorly
to third-line therapies based on particular clinical characteristics such as BMI and renal function.
2. SCOPE:
This Standard Operating Procedure (SOP) is specifically for use in the TriMaster study
3. PURPOSE:
The purpose of this SOP is to describe the procedure for data and sample collection for
Screening/Pre-Baseline assessment of the TriMaster study.
4. DEFINITIONS AND ABBREVIATIONS
The headings below contain the definition of terms and meanings of abbreviations used within
this document.
SOP- Standard Operating Procedure
CRF-Case Report Form
PIS – Patient Information Sheet
CHI – Community Health Index (Scotland only)
5. ROLES AND RESPONSIBILITIES:
It is the responsibility of research staff to read and use this SOP when collecting data
and samples for the Screening/Pre-Baseline assessment for the TriMaster study.
6. SKILL LEVEL:
This procedure should only be carried out by personnel who have undergone the appropriate
training
7. EQUIPMENT:
Study paper work:
 Current version of the TriMaster eligibility screening form
 Current version of the TriMaster consent form x3
 Current version of the case report form (CRF) for TriMaster Screening visit
 Current version of the TriMaster PIS
 Barcode labels for TriMaster Screening visit
 Participant medical records (once consent is obtained)
Anthropometry
 Weighing scales: class 3 (where possible)
 Standard Height measure/stadiometer height measure
Blood sampling
 Standard local venepuncture equipment (see local policy)
 Local venepuncture SOP
 Blood sample tubes as detailed in sample handling section
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SOP Number: NIHRexe/232 TriMaster
Effective Date: 03/04/2017
Version: 2.1
Urine sampling
 Universal urine collection pot/local equivalent
 Local pregnancy testing kit
 Dipstick urine analysis strips and monitor
8. PROCEDURE:
8.1 Prior contact with participant (to arrange screening visit)
Following the initial referral/ identification of a potential participant (via research
database or primary care) and with permission, contact them to discuss the study,
and establish basic eligibility.
This will usually be by telephone:
 Confirm study inclusion and exclusion criteria (see below).Where possible this should be
done against the eligibility screening form. It will not be possible to confirm eligibility from
this information but it will allow some inclusion/exclusion criteria to be established.
 If initially eligible and once the individual has agreed verbally to take part in the study a
PIS should be sent to them confirming the arranged screening appointment date, time
and location, including relevant travel information. This appointment can be carried out
at a location convenient to the participant i.e. (Research centre, primary/secondary care
or home).
 Wherever possible the screening visit and baseline research visit should both be
arranged due to the limited time between these visits.
 Once the screening appointment has been arranged, enter the participant’s data onto
the study database which will allocate a unique screening ID to the participant.
 For instructions on how to create a screening ID in CRF Tracker, please see
Appendix 2.
Telephone screening
Inclusion:
 Clinical diagnosis of Type 2 diabetes
 Age ≥30 and ≤80
 Currently treated with two classes of oral glucose-lowering therapy (given either as
separate or combined medications), that do not include a DPP4-inhibitor, a SGLT2inhibitor or a thiazolidinedione. This is likely to be metformin and sulphonylurea but may
include prandial glucose regulators nateglinide or repaglinide
 No change in diabetes treatment (new treatments or dose change) within previous 3
months
 Able and willing to give informed consent
Exclusion:
 Treated with insulin
 Currently treated with corticosteroids
 Active infection (any infection requiring antibiotics at present)
 Foot ulcer requiring antibiotics within previous three months
 Recent (within 3 months) significant surgery or planned surgery (excluding minor
procedures)
 Pregnant, breastfeeding or planning a pregnancy over the study period
 Concurrent Participation on another Clinical Trial of an Investigational Medicinal
Product
 Unable or unwilling to give informed consent
Page 3 of 10
SOP Number: NIHRexe/232 TriMaster
Effective Date: 03/04/2017
Version: 2.1
8.2 Screening Visit
Prior to the Screening Visit, the participant should be registered in CRF Tracker to generate a
Screening ID.
8.2.1 Obtain written informed Consent
Informed written consent is to be taken by the PI or appropriately trained and
delegated member of the study team.
Prior to any data/sample collection ensure participant is fully informed about the project and their
right to withdraw at any time is given an opportunity to ask any questions, and is happy to
proceed. Ensure written informed consent is obtained on the current version of the study
consent form. Each point on the consent form should be circled and initialled by the participant.
The signed/dated form should be countersigned by the member of staff recruiting and a copy of
the completed document given to the participant at their visit 1 appointment after it has been
signed by the delegated clinician
If consent is taken by a member of the research team other than the PI, or delegated clinician
and the participant wishes to speak to a clinician who is present or contactable via telephone,
further information can be given to the participant and questions can be answered immediately.
Where this is not possible, informed consent should not be taken until the participant is content
that all questions have been adequately answered.
8.2.2 Urine sample – NB This should be done before blood sampling for any female
participants of child bearing potential
 Collect a urine sample in a plain universal container Test urine using local
pregnancy testing kit (follow the instructions contained within the testing kit) a
positive result will exclude the participant from this study.
 Perform urine dipstick analysis. If positive follow local trust procedure for microbiology
and where appropriate advise participate to contact their GP, or inform them directly.
 Records results of pregnancy and dipstick analysis on CRF.
A pregnancy test will be required for all females of childbearing potential. Subjects are
considered not of child bearing potential if they are surgically sterile (i.e. they have undergone a
hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal
(defined as no menstrual period for 12 months without an alternative medical cause).
Females of childbearing potential must be willing to use an effective method of contraception
from the time consent is signed until 7 days after treatment discontinuation, refer to list below.
Contraceptive methods that can achieve a failure rate of less than 1% per year when used
consistently and correctly are considered as highly effective birth control methods. Such
methods include:
 combined (estrogen and progestogen containing) hormonal contraception associated
with inhibition of ovulation:
o oral
o intravaginal
o transdermal
 progestogen-only hormonal contraception associated with inhibition of ovulation
o oral
o injectable
o implantable
 intrauterine device (IUD)
 intrauterine hormone-releasing system ( IUS)
Page 4 of 10
SOP Number: NIHRexe/232 TriMaster
Effective Date: 03/04/2017
Version: 2.1
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bilateral tubal occlusion
vasectomised partner
sexual abstinence
A combination of male condom with either a cap, diaphragm or sponge with
spermicide (double barrier methods) are also considered acceptable, but not highly
effective, birth control methods.
Please inform participants that if they become pregnant during the course of the study, they
must inform the study team including the PI immediately, who should decide appropriate
action. Referral for specialist counselling on the possible risks to the unborn baby should be
discussed and arrangements offered to monitor the health of both the participant and the
unborn baby. Pregnancy must be followed to outcome and outcome reported.
8.2.3 Blood sample collection
 Ensure you have the correct sample collection equipment and blood
collection tubes (see table 1, below)
 Take blood using local venepuncture SOP and draw blood into the tubes.
 Blood samples should be drawn in the following order 1. Serum gel 2. EDTA
plasma
 Label the tubes in line with local laboratory requirements including all
necessary identifiable information. Send to local laboratory. These results will
be used to confirm eligibility for the study.
 Record the number of samples and time collected on the CRF
Primary
Tube
Type
Details:
Small
serum
gel
Small
EDTA
Primary
tube
label /
barcode
Hand
write
centrifuge
primary
sample
Aliquot tube
label/barcode
No
None
aliquots
directions
for primary
tube
None
Direct to
local
biochemistry
department
Table 1
Analysis to request:
 Full, or whole blood count
 HbA1c or glycosylated/glycated haemoglobin
 Serum creatinine levels
 Serum Alanine transaminase levels (ALT)
8.2.4 Data Collection
 At the top of each page of the CRF, please enter two initials for the volunteer. These
relate to the first name and surname.
 Enter the screening ID generated by the study database
 Use the current version of the CRF for TriMaster Screening visit
 Ensure all sections of the CRF are completed.
Page 5 of 10
SOP Number: NIHRexe/232 TriMaster
Effective Date: 03/04/2017
Version: 2.1
The Teleform scanning software requires precise completion of all fields, paying particular
attention to keeping information inside the specified areas. Where boxes (eg:Y/N) need to be
checked, insert an X clearly inside the box
Where 3 boxes are available and your result is two digits, for example a participant who weighs
less than 100kg please ensure you fill all boxes, ie 099.99kg. Please enter free text clearly.
8.2.5 Confirm eligibility
 Check local laboratory blood results to confirm eligibility (refer to inclusion criteria below)
and document on the CRF.
 Check participant medical records to rule out study exclusion criteria (refer to exclusion
criteria below).
Checks should include available hospital notes but if there are concerns about eligibility these
should be addresses by checking the most appropriate medical records.
Countersigning: If a non-clinician obtained informed consent, the consent form needs to be
countersigned by the PI or delegated clinician prior to the IMP being prescribed.
Inclusion Criteria:
 Clinical diagnosis of Type 2 diabetes
 Age ≥30 and ≤80
 Currently treated with two classes of oral glucose-lowering therapy (given either as
separate or combined medications), that do not include a DPP4-inhibitor, a SGLT2inhibitor or a thiazolidinedione. This is likely to be metformin and sulphonylurea but may
include prandial glucose regulators nateglinide or repaglinide
 No change in diabetes treatment (new treatments or dose change) within previous 3
months
 HbA1c > 58mmol/mol (7.5%) – confirmed at screening visit
 eGFR ≥ 60mls/min/1.73m² - confirmed at screening visit
 Able and willing to give informed consent
Exclusion Criteria:
 Changes in glucose-lowering therapy or dose within last 3 months
 HbA1c ≤ 58mmol/mol (7.5%)
 eGFR <60mls/min/1.73m².
 ALT >2.5 x upper limit of the assay normal range or known liver disease, specifically >30
μmol/L that is associated with other evidence of liver failure.
 Currently treated with corticosteroids
 Active infection (any infection requiring antibiotics at present)
 Foot ulcer requiring antibiotics within previous three months
 Recent (within 3 months) significant surgery or planned surgery (excluding minor
procedures)
 Acute cardiovascular episode (angina, myocardial infarction, stroke, transient ischemic
episode) occurring within the previous 3 months
 History of heart failure
Page 6 of 10
SOP Number: NIHRexe/232 TriMaster
Effective Date: 03/04/2017
Version: 2.1
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Current use of loop diuretic therapy (Furosemide or Bumetanide)
History of bladder carcinoma
Current/ongoing investigation for macroscopic haematuria
History of Diabetic Ketoacidosis
History of pancreatitis
Pregnant, breastfeeding or planning a pregnancy over the study period
Concurrent Participation on another Clinical Trial of an Investigational Medicinal Product
Unable or unwilling to give informed consent
8.2.6 Proceeding to Randomisation for eligible participants
 Once eligibility/ineligibility is confirmed, update the screening information on the study
database and click the ‘randomise’ button. This will only be available if eligible screening
data has been entered.
 Once randomised, the ‘Dispense’ button will be available. Press ‘Dispense’ and a bottle
number will be generated based on available packs at the research site. This should be
entered onto the prescription. A ‘Confirmation of Dispensing’ can be generated by
clicking on the bottle number. This should be printed, completed and taken to pharmacy
with the prescription.
 A Study ID will also be generated by the database as part of the randomisation
procedure. This is the participant identifier to be used throughout the study.
 See Randomisation and Unblinding SOP for further details
8.2.7 IMP issue
 Randomisation and dispensing of the study medication must take place before Visit 1. It
is important to discuss with the local pharmacy trial team how much notice they will need
before dispensing prescriptions.
 Complete the prescription template with the participant’s name, NHS/CHI number, study
ID and date of study visit 1. Ensure the prescription is signed by the study clinician and
send to pharmacy.
 The study drugs must be collected from pharmacy on the morning of Visit 1. . In the
event of a home visit, the nurse must still adhere to these instructions, and arrange the
appointment with this in mind. Drugs should not be dispensed prior to the date of the
appointment.
8.2.8 Transferring clinical data to Exeter for processing
 Scan and email the completed CRF to the central Exeter team using the study email
address [email protected]. This must be done within 14 days of
the visit.
 Once the participant has completed screening, ensure the Screening ID, and for eligible
participants the Study ID are written on the countersigned consent form. Scan the
consent form, with the Study ID as the filename (or Screening ID for those who fail
screening) and email a copy of this to [email protected]. This
must be done prior to Visit 1.
Page 7 of 10
SOP Number: NIHRexe/232 TriMaster
Effective Date: 03/04/2017
Version: 2.1
8.2.9 Prior to Visit 1
 The participant’s medical records should be updated with a copy of the signed consent
form, a study PIS and a trial contact sheet/ sticker
 If participants are ineligible following the Screening visit, call the participant to advise,
and cancel the Visit 1 appointment if already arranged. Ensure all study documents are
complete, and update the study database with the reason the participant is ineligible
 If not already arranged agree a date and time with the participant for the Visit 1
appointment. This must be within 2 weeks of the Screening visit.
 Ensure the participant is aware that Visit 1 is a fasting visit and provide them with
appropriate local (10hr) fasting guidelines
9. DESIRED OUTCOME: Comprehensive screening data to establish eligibility and correct
enrolment into the TriMaster study.
10. REFERENCES: NA
Page 8 of 10
SOP Number: NIHRexe/232 TriMaster
Effective Date: 03/04/2017
Version: 2.1
11. APPENDICES:
Appendix 1
Ethnic Group:
Use the standard coding for ethic groups as shown below:
A White British
E White & Black African
J Pakistani
N Black African
Z Not stated
B White Irish
F White & Asian
K Bangladeshi
P Other Black
ZZ Not known
C Other White
G Other Mixed
L Other Asian
R Chinese
D White & Black Caribbean
H Indian
M Black Caribbean
S Any other group
Current Medications
The CRF requires basic information about diabetes and non-diabetes medications being taken.
For diabetes therapies, they may be prescribed more medication, but this list should reflect the
total daily dose actually being taken.
 Record total daily dose of all current hypoglycaemic agents
 A breakdown of each agent (including trade names) in each class of hypoglycaemic is
given below.
 For combined tablets record the constituent medications and doses separately
 Record doses in mg for oral hypoglycaemics, units for insulin, mcg for Exenatide (Byetta)
and mg for Liraglutide (Victoza)
Table 1 – oral hypoglycaemic medication
Treatment class
Possible treatment names (trade names in
brackets)
Metformin (biguanides)
Metformin (Glucophage™, Glucophage SR™,
Bolamin SR™)
Sulphonylureas
Gliclazide (Diamicron™ (SR)), Glimepiride
(Amaryl™), Glipizide (Glibense™, Minodiab™),
Tolbutamide, Glibenclamide
Other OHA
Acarbose (Glucobay™), Nateglinide (Starlix™),
Repaglinide (Prandin™)
Medical history
Please ask the participant questions to identify accurately if they have been diagnosed with any
of the conditions listed and check yes/no as appropriate.
Angina
A volunteer-reported diagnosis of angina will be accepted based on the descriptions of
event(s)/symptoms. Angina can be described as pain, discomfort or pressure in the chest which
often radiates down the left arm. It is also characterised by a feeling of choking, suffocation or
crushing heaviness. In most cases, the symptoms are relieved within a few minutes by resting
or by taking prescribed angina medications (generally GTN spray or tablets). Individuals will
have been subjected to ECG recordings, a stress test and sometimes an angiogram. If you are
unable to make a decision regarding the diagnosis, please circle ‘no’.
Myocardial Infarction (MI)
The volunteer will have been admitted with chest pain and remain an inpatient for ≥ 4 days.
Admission will be to either a CCU or an ITU. They will have had thrombolysis and/or primary
Page 9 of 10
SOP Number: NIHRexe/232 TriMaster
Effective Date: 03/04/2017
Version: 2.1
angioplasty. The angioplasty (usually with stent) will occur on the day of admission and will
have taken place almost immediately on admission. A patient will often know/be able to report
that their Troponin T (TropT) level was raised. A cardiologist will have reviewed the patient.
If the patient has an angiogram at a later date or as an outpatient, is not admitted to a CCU or
ITU and is not seen by a cardiologist, the diagnosis of MI is not accepted and the diagnosis of
angina should be considered.
Stroke (CVE) and Mini Stroke (TIA)
Volunteer-reported diagnosis of a Transient Ischaemic Attack (TIA) will be accepted based on
the description of event/events rather than on a physical examination or neurological
examination.
Common symptoms include loss of movement in the arms, face, or legs, weakness in the legs,
slurring of speech or inability to speak clearly, seeing double or being partially blind, numbness
or tingling of the skin and dizziness.
An attack begins without warning and usually lasts 2 to 30 minutes. Rarely does an attack last
longer than 1 to 2 hours and if an attack lasts more than 24 hours a diagnosis of a Cerebral
Vascular Event (CVE/stroke) is made.
Anthropometry
 Record height (m) and weight (kg)
 Use calibrated class 3 weighing scales and aim to use same scales at later visits
 All measures are to be taken in the same way for males and females
Height:
 Ask the volunteer to remove their shoes and stand on the base plate of the equipment,
with their back to the height scale
 The volunteer should stand as tall and straight as possible with feet together and arms
held loosely at the side and shoulders relaxed
 Adjust the scale so that the head plate rests on the volunteer’s head
 The head should be placed in the Frankfurt Plane, such that an imaginary line joining the
upper margin of the external auditory meatus and the lower border of the orbit of the eye
is horizontal
 Measurers should aim to read the scale from as level a position as possible. If a short
person measures a tall person, or vice versa, considerable error can be introduced
 Record the measurements on the appropriate data collection sheet to the nearest 0.1cm
Weight:
 The weighing scales should be placed on a level surface
 Ensure the scales are at zero when they are switched on
 Aim for the volunteer to be wearing shirt and trousers/skirt only, asking them to remove
heavy items of clothing and jewellery
 Ask volunteer to remove their shoes
 Ask volunteer to stand directly on scales, with weight evenly distributed over both feet
 Measure to the nearest 0.1kg
Appendix 2 CRF Tracker User Guide
Page 10 of 10
SOP Number: NIHRexe/232 TriMaster
Effective Date: 03/04/2017
Version: 2.1