Research Proposal:
Does tranexamic acid reduce post-operative transfusions in patients with
fractured neck of femur: An RCT in the UK.
Contacts:
Mr Ross Coomber, Luton and Dunstable Hospital. Orthopaedic Registrar.
Email: rosscoomber@hotmail.com
Mr Avishek Das, Nottingham University Hospital, Orthopaedic Registrar.
Email:
Mr Norrish, Mr Johnston, Mr Vince, Dr Vindlacheruvu.
Field: Fractured NOF and Tranexamic Acid.
Background:
There is significant morbidity and mortality associated with hip fracture surgery,
this includes bleeding intra-operatively, frequently resulting in post-operative
blood transfusions.
Tranexamic acid (TA) is a pharmacological agent that reduces bleeding by
altering the fibrinolysis pathway, initially its use was restricted for menorrhagia
and within obstetrics and gynaecology.
More recently, good, level 1 evidence has suggested that tranexamic acid reduces
blood loss and transfusion requirements in patients undergoing total hip/knee
arthroplasty and in polytrauma patients. This has been well documented in the
work by Orpen et al, systematic reviews and the CRASH-2 study respectively.
As a result of this evidence tranexamic acid is given routinely for patients with
polytrauma, the first dose often started by the paramedics and the second dose
during the admission.
Additionally, the use of TA is becoming more widespread in lower limb
arthroplasty in the pre and peri-operative period.
The evidence for the use of TA in patients with a fractured neck of femur (NOF)
is less clear. Two studies have been carried out internationally on this subject and
provide some evidence that TA is beneficial to patients with NOF fractures by
reducing intra-operative blood loss, post-operative haemoglobin level drop and
transfusion requirements. There was however an increase in thromboembolic
events in one of the studies in the TA group, although this difference was not
statistically different.
The latest meta-analysis in the BMJ has suggested that there is enough evidence in
the current literature to support the use of TA in arthroplasty and no further
research is required to prove TA’s value in reducing blood loss and transfusion
requirements in this group. However, it does conclude that more research is
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required to establish whether TA use is associated with an increase in
thromboembolic events.
No studies have been performed in the UK and to date there is no meta-analysis to
provide good evidence that TA should be used routinely in patients with fractured
NOFs.
Thus we propose to assess the benefit of TA in patients with a fractured NOF, in
the UK.
Aims and Objectives:
1. To compare placebo versus TA in patients undergoing surgery for fractures NOF
2. To assess blood loss intra-operatively
3. To compare pre and post-operative haemoglobin (Hb) levels
4. To compare transfusion requirements post-operatively
5. To compare length of stay and all cause morbidity
6. To compare prevalence of DVT and PE in both groups
Research questions:
Does TA reduce intra-operative blood loss in fractured NOF surgery?
Does TA reduce post-operative transfusion requirements?
Does TA significantly reduce Hb drop post fractured NOF surgery?
Does TA reduce LOS and all cause morbidity?
Does TA use result in an increase in thromboembolic events in patients with NOF
fractures?
Working Hypothesis:
We hypothesise that tranexamic acid will reduce blood loss and transfusion
requirements in patients undergoing surgery for fractured NOFs, without an
increase in thromboembolic events.
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Study Methodology:
We propose a randomized, double blind, controlled trial comparing placebo versus
tranexamic acid in patients undergoing surgery with fractured NOFs. The study will
be multi-centred and will run prospectively in the two teaching hospitals within the
East of England.
All patients admitted with a fractured NOF will be invited into the study.
Once consent has been gained patients will be randomized into placebo or TA group.
Syringes will be pre-filled with either normal saline or ~mls of TA, which will be given
at induction of anaesthesia and post-operatively at 6 hours.
Pre-operative Hb will be taken and compared to the post-operative Hb at a set time
post-op, within 12 hours.
Intra-operative blood loss will be measured and documented on both the anaesthetic
charts and operative records.
Intra and post-operative transfusions will be recorded. Transfusions will be given as
per standard protocol with Hb <8 etc. If patients require transfusions pre-operatively
will need to be excluded from the study.
All cause morbidity, mortality and length of stay will also be included in the analysis.
Patients will be case matched and randomized by computer generation.
Intervention:
Tranexamic acid or normal saline.
Population:
The population will include all patients willing/able to give consent who present with a
fractured NOF to two teaching hospitals.
Participants will need to give informed consent and should have the opportunity to
withdraw, and withdraw their data, from the project.
The exact size of the sample should be informed by suitable power calculations.
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Research Ethics:
NHS research ethics approval (NRES / IRAS: www.myresearchproject.org.uk) will be
required.
Informed consent will be required from each patient in addition to the standard
consent procedures.
A Participant Information Sheet and Consent Form will need to be developed in line
with NHS research ethics committee guidance.
If we discover adverse effects in the TA group within the trial period, such as an
increase in thromboembolic events the trial will be abandoned. The evidence to date
does not suggest this will occur.
Funding:
Funding will be required for the trial which will be sought. Main costs will be the
randomization, administration, duplex scans and the TA.
References and Further Reading:
1. Pfizer. Study of tranexamic acid for the reduction of blood loss in patients
undergoing surgery for long bone fracture. 2011.
http://clinicaltrials.gov/ct2/show/results/NCT00824564?sect=X6015#outc
ome1.
2. Sadeghi M, Mehr-Aein A. Does a single bolus dose of tranexamic acid
reduce blood loss and transfusion requirements during hip fracture
surgery? A prospective randomized double blind study in 67 patients. Acta
Med Iranica2007;45:437-42.
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3. Katharine Ker, Phil Edwards, Pablo Perel, Haleema Shakur, Ian Roberts. Effect of
tranexamic acid on surgical bleeding: systematic review and cumulative metaanalysis. BMJ 2012; 344 doi: 10.1136/bmj.e3054 (Published 21 May 2012)
4. Zufferey PJ, Miquet M, Quenet S, Martin P, Adam P, Albaladejo P, et al.
Tranexamic acid in hip fracture surgery: a randomized controlled trial. Br
J Anaesth2010;104:23-30
5. The effect of tranexamic acid administered to patients with hip fractures.
Can blood loss be reduced? Hvidovre University Hospital. Trial registered
on clinical trials.gov.
6. The CRASH-2 Collaborators. Effects of tranexamic acid on death,
vascular occlusive events, and blood transfusion in trauma patients with
significant haemorrhage (CRASH-2): a randomised, placebo-controlled
trial. Lancet2010;376:23-32
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