CTG Newsletter October 2014 - Australian and New Zealand

Newsletter No 7, October 2014
The ANZICS Clinical Trials
Group (CTG) Executive
is a standing committee
of the Australian and
New Zealand Intensive
Care Society (ANZICS)
Our Mission
To promote excellence in
Intensive Care medicine
through collaborative clinical
research focused on improving
patient-centred outcomes.
Our Vision
To facilitate and promote
investigator-initiated,
collaborative clinical research
in critical illness throughout
Australia and New Zealand.
To foster and promote multi
disciplinary and international
research collaboration.
To develop high-quality
programs of research
addressing clinically
relevant questions
To advance the education
and understanding of
research methodology
and critical analysis.
Our Values
Innovation, creativity and
intellectual development
of scientific thought.
Respectful and collegiate
relationships within our group,
the intensive care community
and with collaborators.
Integrity, responsibility and
accountability to ourselves, our
patients and the community.
From the CTG Chair In our 20th anniversary year, we
are delighted to congratulate John
Myburgh, who became an Officer of
the Order of Australia in the Queen’s
Birthday honours. John has made a
major contribution to the development
of intensive care research in Australia
and New Zealand, and continues to
lead the Division of Critical Care and
Trauma at the George Institute for
International Health, which has been a
key collaborator in major CTG projects
throughout our 20-year history.
Congratulations also to Sandy Peake
and all the ARISE investigators with
the publication of the study in the
New England Journal of Medicine
and simultaneous presentation at the
European Society meeting in Barcelona.
This is the 10th CTG publication in the
Journal, and I’m sure we can expect
more over the next few years. Other
studies are also progressing well: BLING
II, HEAT have all recently completed
recruitment and we look forward to their
results over the next few months once
follow-up and analysis is complete.
There remain a significant number
of major studies actively recruiting
including ADRENAL,
TRANSFUSE,
EPO-TBI, POLAR, PHARLAP, SPICE,
RELIEF, and PATCH. The first CTG
cluster-crossover trial, SPLIT (a pilot
study of 0.9% saline vs Plasmalyte) has
recruited 2000 patients in 6 months in 4
NZ ICUs, and will pave the way for more
studies using this design. The Point
Prevalence Programme undertook its
8th day on 24 September, and continues
as a valuable source of observational
data for study development.
So far this year there has been mixed
success with funding applications.
SPICE ($1.18M) and RELIEF ($0.77M)
were successful with project grants from
the Health Research Council of New
Zealand in June. SuDDICU (selective GI
tract decontamination) was also awarded
$1.2M by the HRCNZ, but as this is
the first funding for this international
collaborative study, these funds will
only be able to used if other countries’
applications
are
also
supported.
Unfortunately, both applications to the
NHMRC from the ANZIC-RC for Centres
for Research Excellence grants (a
global collaboration in severe traumatic
brain injury, and long terms outcomes
from critical care) were not successful.
Results of project grant applications to
the NHMRC for TARGET (augmented
vs. reduced goals for energy delivery),
REVITALISE (Vitamin D supplementation
in critical illness), the ARISE/ProCESS/
PROMISE individual patient data metaanalysis, TEAM (trial of early activity
and mobility) and SuDICCU will be
known in early November. Applications
for the next HRCNZ project grant round
are also underway for PEPTIC (cluster
study of stress ulceration prophylaxis
using existing data sources), PATCH
(prophylactic tranexamic acid in trauma)
and TARGET.
A recent significant development
in research funding has been the
allocation of infrastructure support
from the HRCNZ for intensive care
research at the Wellington-based
Medical Research Institute of New
Zealand. This provides an opportunity
to co-ordinate multi-centre ICU research
through what may develop into a third
“methods centre” working with the
CTG. In other areas of collaboration,
through the CTG’s involvement in the
International Severe Acute Respiratory
and Emerging Infection Consortium
(ISARIC) we will be participating in a
global short period incidence study of
severe respiratory infection planned for
winter 2015 which will provide baseline
data and capacity-building for a new
major outbreak, and work is continuing
on the design of a global adaptive trial
of several interventions in community
acquired pneumonia with the European
‘PREPARE’ consortium.
A new issue for the CTG is how
the developing campaign for open
access to pharmaceutical company
trials data will affect collaborative trials
Report from the Chair cont.
groups. Although the principle is, in general,
strongly supported by independent academic
researchers, when there is a commercial
aspect to an independent trial, the resource
imbalance in analysis capacity and publicity /
marketing is of concern. This is currently an
issue for the CHEST management committee,
and the CTG will need to develop a position
to include in the requirements for CTGendorsed studies. This will take some time and
debate, and I encourage you to communicate
your views and ideas to CTG Committee
members.
Another area of concern is the interaction
between the ethical and legal requirements
relating to consent for research involving
incompetent adults. There is not always
an appropriate synergy between these two
dimensions in the various local jurisdictions
and has been illustrated recently with some
NSW Guardianship Tribunal decisions, and in
New Zealand closer attention to the difference
between the legal and ethical situation by ethics
committees has led to some increased media
attention.
Finally, a very successful CTG Winter
Research Forum was held in Sydney on 21–22
August at Crowne Plaza Coogee Beach Hotel.
Prior to the main meeting, a 2-day course on
“Clinical Research: A Guide to the Dark Arts” was
held in conjunction with the ANZIC Research
Centre at Monash University, and Manoj Saxena
ran a one-day workshop on “Normothermia
for Acute Neurological Injury”. Looking ahead,
the annual Noosa meeting will be 4 – 6 March
2015, and Yaseen Arabi, a major collaborator
in CTG studies from Saudi Arabia, will be our
international guest speaker.
Colin McArthur
CTG Chair
[email protected]
2014-15 Intensive Care Foundation Grants
Dr Gill Hood, Intensive Care Foundation Chair, announced grants totalling more than $212,000
at the ANZICS/ACCCN Annual Scientific Meeting gala dinner, held in Melbourne on Saturday,11
October.
The Foundation is dedicated to supporting research into intensive care and critical illness. Since
2000, it has granted more than $2.8 million to researchers in Australia and New Zealand, funded
through a combination of public donation and corporate sponsorship.
In announcing the Grants, Dr Hood commented on the Board’s satisfaction that, in addition to
the two Trainee Project Grant recipients, four of the nine other Foundation Grants were awarded to
novice researchers. Providing early opportunities for talented young researchers to ‘kick-start’ their
careers remains a priority for the Foundation.
Pharmacokinetic Australasian
Collaborative
Funding: $39,156
Prof. Jeffrey Lipman
TxA levels in the PATCHTRAUMA trial
Funding: $38,350
Prof. Michael Read
Fisher&Paykel Research Grant
Incidence, Risk Factors,
Consequences and Treatment
of Ventilated Patients with
Nosocomial Infection with
Pandrug Resistant Organisms
in Hospitals in Asia
Funding: $34,000
Dr Steve McGloughlin
The peptic study
Funding: $25,000
Dr Paul Young
Can individualized blood
pressure targets reduce the
risk of new onset acute kidney
injury among critically ill patients
with shock - a pilot before
and after feasibility study
Funding: $22,800
Dr Rakshit Panwar
Identifying the Genetic Cause
of Fatal Pseudomonas
Funding: $15,062
Dr Luregn Schlapbach
Central venous Access
device SeCurement And
Dressing Effectiveness:
the CASCADE pilot trial
Funding: $12,240
A/Prof. Marion Mitchell
Haemodynamic Effects of
Intravenous Paracetamol
in Healthy Volunteers
Funding: $7,814
Ms Elizabeth Chiam
Trainee Project Grants:
Gallbladder Motility
in Critical Illness
Funding: $5,000
Dr Mark Plummer
The Endothelial Glycocalyx in
Acute Traumatic Coagulopathy
Funding: $3,400
Dr Elissa Milford
A Discrete Choice Experiment
to evaluate clinician
preference regarding
resuscitation fluid selection
Funding: $9,500
Mrs Naomi Hammond
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News from the Victorian
IRCIG Branch
Clinical trials in Victorian intensive care units (ICUs) continue to be
extremely well supported. There are 15 Victorian adult and paediatric ICUs
affiliated with the ANZICS Clinical Trials Group. In addition, we are in the
very fortunate position of having good representation of both metropolitan
and regional hospitals.
Previously, to foster a collaborate spirit we have held annual research
meetings. Our most recent meeting was hosted by Ms Samantha Bates
and was held at the Western Hospital. We thank her for her time and effort.
As a side comment it is always valuable to experience research from within
other settings. New ideas, tips and tricks are always beneficial.
While the high recruiting trial ‘CHEST’ has recently left us, many Victorian
sites are now participating in ADRENAL, SPICE and TRANSFUSE.
Importantly, while these studies will provide evidence to support patient
care they also provide per patient payments that can provide funding
support to RC positions.
For new IRCIG RC members, Ms Pauline Galt (Monash Health) is our
Victorian regional IRCIG representative. Pauline has a wealth of clinical
trial knowledge and experience, so please do not hesitate to contact
her. I urge new investigators/members to visit the IRCIG homepage via
http://www.anzics.com.au/ctg/ircig to learn more about the IRCIG
community and upcoming ANZICS Clinical Trials Group trials.
Pease save the date – Tuesday, 3rd March 2015. This is the ICU
Research Coordinator Workshop 2015 (held the day prior to the ANZICS
Clinical Trials Group meeting, 4th-6th March, 2015). The program is
shaping up to provide a wealth of information. It should be a terrific day.
Adj. A/Prof Glenn Eastwood
IRCIG Vice Chair
Austin Hospital, VIC
[email protected]
“...it is
always
valuable to
experience
research
from within
other
settings.
New ideas,
tips and
tricks are
always
beneficial.”
News
from the
Victorian
IRCIG
Branch
Victorian Research Coordinators at the 2014 Annual Research Meeting of the
Victorian IRCIG Branch, hosted by Ms Samantha Bates, Western Hospital.
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study spotlight
The Baby SPICE Programme
The administration of sedative and analgesic agents is almost universal among
critically ill children who receive invasive mechanical ventilation whilst admitted
to an intensive care unit. However, the evidence to support sedation strategies and
guidelines for critically ill children is based on a limited number of small studies.
These studies suggest that:
1. Strategies in which targeted light sedation or daily interruption of sedative
drugs have been shown to reduce duration of ventilation and ICU stay
2. Current sedatives used may be associated with both
short and long term adverse effects
3. Central alpha-2 agonist sedative drugs have been shown
to be safe and effective in critically-ill children
Studies in adult intensive care have also demonstrated an association between
early deep sedation and potentially significant adverse outcomes. However, there
are no adequately powered well designed randomised studies into the practice
of sedation in children which assess the impact of sedation on patient-centred
outcomes, such as length of ICU stay, mortality or long-term cognitive function.
There is also growing evidence in adult intensive care that sedation strategies which:
1. are commenced early after initiation of mechanical
ventilation to maximise potential benefits
2. rely predominantly on central alpha-2 receptor agonist sedative drugs, that
appear to reduce the duration of mechanical ventilation and delirium; and
3. apply a strategy of targeted light sedation (wakefulness), that
appears to minimise the complications of deep sedation
may reduce duration of mechanical ventilation and
possibly improve long-term outcomes.
The rationale of the Baby SPICE Programme is to test these sedation strategies in
mechanically ventilated, critically ill children.
This phase III multicentre randomised controlled trial, currently in
development, is the fourth and final step in the Baby SPICE Programme
which has previously performed or is in the process of:
1. Point prevalence study of sedation in Australian and New Zealand paediatric
intensive care units
Data were collected on 83 patients in 14 intensive care units, 88% being PICU
admissions. Thirty-seven patients were ventilated. Of these patients, sedation
assessment occurred in 65% using a validated scale. Patients were optimally
sedated in 44% of cases. Under- and over sedation occurred in 10% and 46%,
respectively. Deep sedation was clinically indicated in 30% of patients. Pain
assessment occurred in 38% using a validated scale. Formal assessments
of delirium were not conducted, however of the 20 patients assessed for
manifestations of delirium; 25% had sleep/wake cycle disturbances; 20% had
psychomotor agitation/retardation; and 10% had inattention, anxiety, moaning
and restlessness.
2. Baby SPICE Observational Study comparing sedation practices, sedation
levels and outcomes in children in ANZ PICU’s
This multicentre longitudinal observational cohort study into sedation practice
in 8 paediatric intensive care units in Australia and New Zealand confirmed
significant practice variability with no clear preference for a particular sedative
regimen. Midazolam was the most commonly prescribed drug for sedation in
ventilated patients (74% of patients) compared to dexmedetomidine (31.8%) and
clonidine (28.3%).
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Image by Simon Erickson
A majority of children were deeply sedated at baseline
(62%) and at 48 hours (74.5%). There was also a significant
association between deep sedation in the first 48 hours
and length of mechanical ventilation (p=0.002) and length
of ICU stay (p=0.08).
Studies in adult intensive care have also demonstrated an
association between early deep sedation and potentially
significant adverse outcomes. However, there are no
adequately powered well designed randomised studies
into the practice of sedation in children which assess the
impact of sedation on patient-centred outcomes, such
as length of ICU stay, mortality or long-term cognitive
function.
3. Baby SPICE Pilot Randomised Controlled Trial
comparing Early Goal Directed Sedation versus
Standard Sedation
This is a pilot prospective randomised controlled trial
that will be conducted in six tertiary paediatric intensive
care units in Australia and New Zealand and will recruit
60 patients with a maximum of 15 patients from
each participating site. The study will recruit patients
ventilated for less than 12 hours, who are expected to
remain ventilated at least 24 hours after enrolment AND
need immediate and ongoing sedation. Patients will be
recruited into one of two study groups. The intervention
arm will receive dexmedetomidine as the primary agent,
with the addition of second line sedatives as required. The
control arm will have sedation according to usual practice
as chosen by the treating clinician. In both groups, the
default sedation level is light sedation, as defined by
a target State Behaviour Scale (SBS) of -1 to +1, unless
otherwise specified by the treating clinician. The primary
outcome measure for the pilot study is to demonstrate
separation between the intervention group (GpDex) and
a standard practice control group (GpStd) with respect to
the proportion of patients achieving light sedation (SBS -1
to +1) in the first 48 hours of sedation in intensive care.
4. Phase III Multicentre Randomised Controlled Trial comparing Early Goal
Directed Sedation to Standard Sedation
An NHMRC Grant Application to fund this trial is currently in development, and
will include information attained from the Point Prevalence, Observational and
Pilot studies. For the phase III trial we will be looking at duration of mechanical
ventilation as a patient-centred outcome. As mortality is low in PICU (even in
this targeted group-around 6-7%), duration of mechanical ventilation is the
most suitable primary outcome. The sample size for this study will be over 600
patients which is a very large trial in PICU.
Baby SPICE
Management
Committee:
Simon Erickson
(Chair / Project
Manager)
Debbie Long
(Co-chair)
John Awad
Brian Anderson
John Beca
Carmel Delzoppo
Marino Festa
Johnny Millar
Mary Lou Morritt
Yahya Shehabi
Claire Sherring
Tony Slater
I would like to thank my co-committee members for their help with this
programme. I would also like to thank everyone from the ANZIC-RC and SPICE
MC, especially Belinda Howe, for their help and advice with this study.
Dr Simon Erickson
Baby SPICE Management Committee Co-Chair / Project Manager
[email protected]
5
study spotlight
The IRONMAN Study
Intravenous Iron or Placebo for Anaemia
in Intensive Care: ‘The IRONMAN study’ is a
phase II randomised controlled trial designed to
determine whether intravenous iron compared
with placebo in patients admitted to the ICU
and who are anaemic, reduces red blood cell
(RBC) transfusion requirement.
Nearly 20% of all RBC units in Australia are
administered to patients in the ICU. The most
common indication for ICU RBC transfusion is
anaemia despite extremely high concordance
with restrictive transfusion guidelines. Both
anaemia and RBC transfusion are associated
with increase morbidity and mortality, and
allogenic blood is also an increasingly scarce
and expensive resource. There is therefore an
urgent need for novel interventions designed to
reduce anaemia and RBC transfusion.
The IRONMAN study is funded by a
competitive grant from the State Health
Research Advisory Council (Western Australia)
with product support provided by Vifor Pharma.
The study is recruiting in five sites in WA
(RPH, Fremantle Hospital, Sir Charles Gardner
Hospital, Joondalup Health Campus and
Armadale Hospital) and has now enrolled 90 of
the planned 140 participants.
In addition to the primary endpoint of RBC
transfusion, the trial will undertake an economic
analysis of RBC transfusion and IV iron as well
as collect data to examine the role of hepcidin,
the master regulator of iron metabolism, in
critical illness.
On behalf of the management committee,
I would like to thank all the sites for their
continued hard work and hope to complete
the study in time to report results at the 2015
Winter Research Forum.
Dr Ed Litton
Chief Investigator
IRONMAN Study
[email protected]
Update from the
Medical Research
Institute of New
Zealand (MRINZ)
The Medical Research Institute of New
Zealand
(MRINZ)
is
working
towards
establishing itself as the New Zealand clinical
methods centre for ANZICS CTG studies.
The recent completion of the HEAT study
was a major milestone for the MRINZ and for
New Zealand ICU research generally as it was
the first CTG trial funded and led from New
Zealand.
Recruitment for the SPLIT study, which
is being conducted in four NZ ICUs, will be
completed on the 14th of October. The SPLIT
study has recently enrolled its 2000th patient
and has run very smoothly.
Following on from the success of these
studies, the MRINZ will act as the methods
centre for the NZ arm of the RELIEF study and
we hope that other studies will follow.
The major New Zealand health research
funding round is underway and funding
applications have been submitted through the
MRINZ for major studies including TARGET
and PATCH. Rachael Parke’s Cardiac Fluid
study and the PEPTIC study have also been
submitted for HRC funding.
Dr Paul Young
[email protected]
6
5th Annual CTG Winter Research Forum
Dr Shay McGuinness
Meeting Convenor
meeting report
The 5th Annual CTG Winter Research Forum
was held at Coogee Beach in Sydney on the 21st
& 22nd August. Around 85 people attended what
was a very full program over the two days. In
addition to the usual assortment of new proposals
and updates on the progress of ongoing studies
there was time for a full session detailing the
benefits and pitfalls of interacting with industry
for support of clinical research. There is general
agreement that we will require some form of
industry support for many of our trials to be
“financially” feasible and the CTG does have
guidelines to help govern this.
There was also a presentation by Jamie
Cooper and John Myburgh explaining what the
two Australian Research Methods Centres do
(The ANZIC Research Centre in Melbourne and
the George Institute in Sydney),
as well as information about the
formation of a New Zealand centre
at the Medical Research Institute of
New Zealand by Paul Young.
Imogen Mitchell gave a fantastic
overview of her recently completed Harkness
Fellowship and Steven Webb completed an
excellent meeting with an overview of the
planned International Bayesian Adaptive Trial
in Community Acquired Pneumonia as well as a
proposed observational study.
Many thanks to all the speakers for their
excellent presentations and for the interactive
involvement of the audience, helped considerably
by a “soft ban” on personal computer use during
presentations! Also thanks to Donna and Simone
for a perfectly run meeting. Save the dates for
next year – 9th-10th July (see below).
Developing links
with established
and emerging
clinical trials
groups
Dates for the Diary:
The 6th Annual ANZICS Clinical
Trials Group Winter Research Forum
will be held Thursday 9th - Friday
10th July 2015 at the Sea World
Resort, Gold Coast Australia.
One of the aims of the CTG is to foster
links with other trials groups and to help
new groups get established. We have
previously been involved in running
Research Foundations Workshops in
Singapore, in conjunction with InFACT
and the Asian Critical Care Clinical
Trials Group. Earlier this year we were
involved in running a workshop in Rio
aimed primarily at training emerging
researchers. We also had CTG and
IRCIG representation at the second
annual meeting of LACTIN (The Latin
American Clinical Trials Network)
allowing some discussion of both our
model of the conduct of clinical trials,
especially around the essential role of
the Research Coordinator, and some
discussion of the practical aspects of
some proposed projects.
Dr Shay McGuinness
Chair CTG Capacity Working Group
7
Point Prevalence Program
The CTG Point Prevalence Program (PPP) is conducting its 8th Study Day
in 2014, six years after the program commenced in 2009. The PPP continues
to be an important part of the research infrastructure of the ANZICS Clinical
Trials Group, providing observational data to describe current practice and
support future research and major grant applications. The program has
recently received positive global attention, being commended in Pediatric
Critical Care Medicine as a unique program of research comprised of a stable
network of sites and approved under an ‘umbrella’ protocol in order to minimise
the administrative burden on sites and allowing the epidemiology of critical
illness to be continuously reassessed [Weiss et al, PCCM, 2014, 15:660-666].
Study Day 8, set for September and October 2014, is examining ‘Treatment
Intensity in Intensive Care’ as well as assessing current practice surrounding
the use of Maintenance Fluids, Electrolyte Replacement and Stress Ulcer
Prophylaxis. We look forward to sharing the findings of these studies with you
in 2015.
The PPP remains open for business and we encourage all ICUs across
Australia and New Zealand to get involved! Young investigators wishing to get
some baseline observational data with the support of a team of experienced
researchers are strongly encouraged to utilise the program. Additionally the
PPP is a great starting point for sites that are new to research.
Please contact the team at The George Institute ([email protected])
if you have any enquiries or wish to contribute to this highly successful and
valuable program of research.
Thank you!
A/Prof Ian Seppelt (Program Convenor)
and Ms Kelly Thompson (Program Coordinator
[email protected]
The Dark Art of Clinical Research
News from the ANZIC Research Centre
The ANZIC-RC in conjunction with the ANZICS-CTG recently ran the
second “Clinical Research: A Guide to the Dark Arts” course. The course
was held at Crowne Plaza Coogee, and preceded the ANZICS-CTG Winter
Research Forum.
More than twenty researchers with backgrounds in Intensive Care,
Anaesthetics, Infectious Diseases and Haematology participated. Topics
were wide ranging including “Philosophy and the medical researcher”,
“Strategic planning”, “Marketing and branding”, and “How to choose what
to research”. Participants fed back that the interactive writing workshop,
involving some homework prior to the course, was particularly constructive.
The course was led by Steve Webb with able assistance from that very
influential scientific mind, Rinaldo Bellomo. Additional presenters included
Colin McArthur, Shay McGuinness, Lisa Higgins and Lynne Murray.
Participants were also treated to stimulating presentations from guest
presenter, Rhiannon Tate, Executive Officer of the Australian Clinical Trails
Alliance.
Social activities were not forgotten, with a well-attended Thai dinner, where
lively discussion continued about the “Dark Arts”. On closing night the rather
weary but inspired participants and presenters retired to the bar to toast the
conclusion of another successful course.
Ms Lynne Murray, Research Centre Manager
ANZIC Research Centre
[email protected]
www.anzicrc.monash.org
8
The CTG was asked to convene a
session within the recent ANZICS/
ACCCN ASM in Melbourne titled ‘ANZICS
CTG – critical care research at its best’.
A themed session on sedation was ably
put together by four investigators from
the SPICE management committee Yahya Shehabi, Frances Bass, Michael
Reade and Belinda Howe.
In
keeping
with
the
rigorous
and methodical process that has
characterized the SPICE program of
research to date, the four sequentially
presented the evidence in support of
sedation strategy and its association
with outcomes in the critically ill, the
tricks and traps in recognising delirium in
the ICU, difficulties in conducting
research on established delirium
(including a teaser on the
preliminary results from DahLIA
by Michael Reade), and finally,
how the available evidence
guided the design of the SPICE
III RCT.
In
demonstrating
the
progression of the SPICE program from
observational data, through piloting
the intervention of interest, to the final
NHMRC funded multicentre RCT, the
speakers more than lived up to the billing
of the session and provided an extremely
useful platform for an interactive session
well represented by all members of the
ICU multidisciplinary team.
We are extremely grateful to the four
presenters for giving their time and
energy to the session and look forward
to the success of an extremely important
and well designed trial.
meeting report
The CTG session at
the ANZICS/ACCCN
ASM, Melbourne 10th October 2014
Dr Rachel Parke & Dr Ed Litton
(Co-conveners, CTG session ANZICS ASM)
Dates for the Diary:
The 17th Annual Meeting on Clinical Trials in Intensive
Care (Noosa) will be held Wednesday 4th - Friday 6th
March, 2015. This meeting will be immediately preceded
by the ICU Research Coordinator Workshop 2015.
In 2015 we are pleased to be returning to the Sheraton
Noosa Resort & Spa. Registration details for the meeting
will be released in mid-November. Please keep your eye
on the CTG Mailing List for further announcements.
ANZICS Clinical Trials Group
Executive Office
PO Box 164
Carlton South
VICTORIA 3053
p. +61 (0)3 9340 3455
f. +61 (0)3 9340 3499
[email protected]
Donna Goldsmith
CTG Executive Officer
Simone Rickerby
CTG Executive Assistant
9