eudract number: 2009-012575-10 isrctn number: isrctn02734162 chief investigator: dr simon langton...
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EudraCT number: 2009-012575-10
ISRCTN number: ISRCTN02734162
Chief Investigator: Dr Simon Langton Hewer
Co-Investigator:Prof Alan Smyth
Trial Co-ordinator:Hannah Short
Trial of Optimal TheRapy for Pseudomonas EraDicatiOn in Cystic Fibrosis
Mucoid PA, development of biofilm
Birth First PA culture
Second PA culture
PA free interval
Persistent PA infection
Intermittent infection Chronic infection
Natural history of acquisition of Pseudomonas aeruginosa
Adapted from Rosenfeld NACFC, Minneapolis 2009
Consequences of infection with Pseudomonas aeruginosa
• Reduced FEV1 during childhood
• Faster decline in FEV1
• More rapid decline in CXR score• Reduced growth, QoL• Increased hospitalisation and need for antibiotics• Reduced adult survival• Impossible to eradicate once chronic infection is
established
There are now 68 sites in the UK open to recruitment of which 58 are paediatric sites.
Study Update – Sites
First site opened to recruitment in June 2010.
Since October 2010 we have recruited a total of 132 patients.
Our next key target is to recruit 200 patients by the end of May 2014.
If we achieve this milestone the study team will request an extension to the recruitment period to enable us to reach our original target of 280.
Study Update – Recruitment
Jun-10Jul-1
0
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-11
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-12
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-13
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Monthly Accrual % of total sample size
TORPEDO Monthly and Cumulative Accrual to 30/08/2013
Study Update – Recruitment
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Jan-14
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Revised expected centres
1 5 7 8 9 9 10 12 14 16 17 18 19 21 23 27 31 35 37 39 44 48 52 55 55 55 55 55 55 55 55 55 55 55 55 55 55 55 55 55 55 55 55 55 55 55 55 55
Current centres
1 5 7 8 9 9 10 12 14 16 17 18 19 21 23 27 31 35 35 37 41 42 45 50 51 53 54 56 59 62 63 64 67 67 69 69 69 68 68 NaN
NaN
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Revised expected recruitment
NaN
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22.4599289215074
25.4319646139132
28.8450717348904
32.6046990023878
36.677513083072
41.11979103322
46.1802508015499
51.8774109065801
58.0597561967955
64.427286672196
70.7948171475965
77.1623476229971
83.5298780983977
89.8974085737982
96.2649390491988
102.632469524599
109
115
121
127
133
139
145
151
157
163
169
175
181
187
193
199
Current recruitment
0 0 0 0 2 3 5 9 10 12 13 14 15 17 17 18 20 22 27 35 39 43 48 51 59 66 72 77 84 91 95 98 100
108
114
117
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128
NaN
NaN
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25
75
125
175
225
5
15
25
35
45
55
65
75
Nu
mb
er
of
pati
en
ts r
and
om
ise
d
Nu
mb
er
of
cen
tre
s o
pe
n
TORPEDO current and revised expected recruitment as of 31st August 2013
Study Update – Recruitment at Sites
Addenbro
okes, C
ambrid
geBath
Heartl
ands, B
irmingh
am (A
dult)
Derrifo
rd, P
lymouth
Eastb
ourne
Glouceste
rshire
Royal
Hillingd
on
Ketteri
ng Dist
rict G
enera
l
Leigh
ton, C
rewe
Oxford
Children
s
Pilgrim
Royal D
evon &
Exete
r (Adult)
South
ampto
n
Torb
ay (A
dult)
Chesterfi
eld
Conquest
Derrifo
rd, P
lymouth
(Adult)
Edinburgh
New Cro
ss, W
olverh
ampto
n
Portsmouth
Brighto
n
Sheffi
eld Child
rens
Wyth
ensh
awe,
Manch
ester
Musgrove
Park, T
aunto
n
Norfolk
& Norwich
Royal C
ornwall
Royal P
resto
n
St Jam
es, Le
eds
Wals
grave
, Cove
ntry
James
Cook
King's Colle
ge
King's M
ill
Linco
ln County
Royal B
rompto
n
North St
affs
Great O
rmond St
reet
Leice
ster C
hildren
s
Royal D
evon &
Exete
r
Nottingham
Children
s
Alder Hey
, Live
rpool
Birmingh
am Child
rens
Bristo
l Child
rens
0
2
4
6
8
10
12
Number of patients recruited into TORPEDO-CF by site to 31st August 2013
The original feasibility study predicted that approximately 45% of eligible patients would agree to take part in the trial.
The latest screening data shows that approximately 40% of eligible patients have consented to take part in the trial.
The screening data shows that the main reasons given for non-consent of eligible patients have been patient preference for either IV or oral antibiotic treatment.
Study Update – Screening and Recruitment
Does not want to be randomised
Does not want to receive IV treatment
Does not want to receive oral treatment
Does not want to attend follow-up
Family circumstances
Other reason*
No reason provided
Why did families say "No"? (as of 30th June 2013 179 eligible patients or their parents have said “No")
Other reasons:1New diagnosis not sure about research2Patient declined study does not want eradication therapy
Recruitment issues
Issues with Recruitment
• Team Approach to TORPEDO trial
• Determination to reach target of 280 recruits
• Likely to be achieved if every eligible patient is approached by senior member of CF team
• CF teams will need resources for this – MCRN, CLRN
• Helpful where these eligible patients are already aware of the study and the CF team is enthusiastic about their participation and the importance of their involvement in answering the question of IV superiority over oral therapy
• Having come this far we need to achieve the target!
• Avoidance of ‘Trial fatigue’
Recruitment issues
• Competing studies
• Availability of beds
• Duration of trial treatment
• Patient preference
• Other issues?
Recruitment issues
• Competing studies
• Availability of beds
• Duration of trial treatment
• Patient preference
• Other issues?
Pa recurrence occurred in 104/298 (35%) trial participants and in 295/549 (54%) historical controls over 15m
Recruitment issues
• Competing studies
• Availability of beds
• Duration of trial treatment
• Patient preference
• Other issues?
“We decided to take part in the trial
because we want to help improve
the care for cystic fibrosis patients.
As a nurse, part of my job is to
provide best evidence practice and
without research being carried out
you haven't got that evidence.”
A big thank you for all your support with the study!
Every recruit counts so if there is anything we can do to help please don’t hesitate to contact us.
Clinical Trials Unit Contact Details:
Trial Co-ordinator: Hannah ShortTelephone: 0151 282 4714
Email: [email protected] Website: www.torpedo-cf.org.uk
And finally……….
http://www.torpedo-cf.org.uk
Acknowledgements:
Trial Management Group (TMG)Dr Simon Langton Hewer Chief InvestigatorDr Alan Smyth Co-InvestigatorProfessor Rachel Elliott Lead Health EconomistProfessor Deborah Ashby Lead StatisticianMr Ashley Jones Senior Trial StatisticianMiss Michaela Blundell StatisticianHelen Hickey Senior Trial ManagerHannah Smith Trial Coordinator Trial Steering Committee (TSC)Professor Jonathan Grigg Independent ChairpersonDr Ranjit Lall Independent StatisticianMiss Sophie Lewis Independent Layperson
Independent Data and Safety Monitoring Committee (IDSMC)Dr Bob Dinwiddie Chairman, Paediatric Respiratory PhysicianProf Christiane De Boeck Respiratory PhysicianMrs Enid Hennessy Expert in Statistics