With the aim to restrict inappropriate FFP transfusions to critically ill patients, a randomized clinical trial will be conducted in a subgoup of ICU patients undergoing an invasive procedure. The objective is to assess the effectiveness and costs…
ID
Source
Brief title
Condition
- Coagulopathies and bleeding diatheses (excl thrombocytopenic)
- Lower respiratory tract disorders (excl obstruction and infection)
- Therapeutic procedures and supportive care NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome of this study will be a procedure-related relevant
bleeding, occurring within 24 hours after the procedure.
Relevant bleeding will be defined using a validated tool for assessment of
bleeding in the critically ill by: overt bleeding with anyone of the following:
-a decrease in haemoglobin by more then 20 g/l in the absence of another cause
-transfusion 2 or more units red cells without an increase in haemoglobin
-a decrease in systolic blood pressure by more then 20 mmHg
-an increase in heart rate of 20 beats/min,
-bleeding at a wound site requiring an intervention (for example,
re-operation).
An assessment of bleeding will be standardized and performed by an independent
research physician or intensivist blinded to the transfusion strategy 1 and 24
hours after the procedure and when clinically indicated. The assessment will
consist of a physical examination, inspection of chest drain production. Also,
haemoglobin will be measured at 1 and 24 hours after the procedure and when
clinically indicated. A chest radiograph will be made to capture intra-thoracic
bleeding. Hemodynamic parameters (blood pressure and heart rate) will be
recorded by an electronic patient data monitoring system.
Secondary outcome
Secondary outcomes:
- minor bleeding within 24 hours
- onset of acute lung injury within 48 hours.
- correction of INR to < 1.5, (after the transfusion and before the procedure,
only in intervention arm) and effect on other coagulation parameters
- length of ventilation days
- length of ICU stay
- ICU mortality
- serious adverse events
- costs
Background summary
Fresh frozen plasma (FFP) is an effective therapy to correct for a deficiency
of multiple coagulation factors. International guidelines support its use in
the case of bleeding in patients with such a deficiency. Use of FFP has grown
steadily in the past years, in particular in the Intensive Care Unit (ICU).
Nationally, approximately 90.000 FFP units are issued (personal communication
with National Blood bank supply). In our ICU, 1.100 units of FFP are transfused
annually, which accounts for 21% of our hospital FFP transfusions.
In the last decade, use of FFP has expanded to include prophylactic
administration of FFP. However, there are concerns about the efficacy of FFP to
prevent bleeding. Evidence from randomized controlled trials that support FFP
transfusion to correct coagulopathy before an invasive procedure is limited,
including commonly performed procedures on the ICU, such as insertion of a
central venous catheter, a chest drain or a percutaneous tracheotomy.
Retrospective studies suggest that the risk of bleeding after an invasive
procedure is low. Relevant bleeding requiring blood transfusion or an
intervention is less then 1 %.
Prophylactic FFP does not further reduce bleeding incidence, but carries the
risk of development of acute lung injury, occurring in up to 30 % of transfused
ICU patients, resulting in an increased length of mechanical ventilation and
ICU stay. However, despite the absence of evidence, in our ICU patients, 33% of
plasma is transfused in the absence of bleeding, which is in accordance with
reports from ICU*s in Europe and the US. We performed a survey on national
practice, revealing that approximately 50% of intensivists administer
profylactic FFP to patients with a coagulopathy undergoing a percutaneous
tracheotomy. This practice may add up to an estimated national number of 10.000
units of FFP for prophylactic use per year.
The use of prophylactic FFP may be explained by the fact that ICU patients are
thought to have an increased bleeding tendency, reflected by prolonged
coagulation screening tests. In ICU patients, the majority indeed has a
prolonged INR. In addition, ICU patients frequently undergo invasive
procedures, which carry the risk of bleeding. Studies on transfusion practice
point to the assumption of ICU physicians that FFP corrects coagulopathy,
thereby preventing bleeding.
Study objective
With the aim to restrict inappropriate FFP transfusions to critically ill
patients, a randomized clinical trial will be conducted in a subgoup of ICU
patients undergoing an invasive procedure. The objective is to assess the
effectiveness and costs of omitting prophylactic FFP transfusion compared to
current practice of prophylactic transfusion, in non-bleeding ICU patients with
a coagulopathy.
Study design
Study design: prospective, multicentre, randomized, open-label, blinded end
point evaluation (PROBE) design.
Intervention
Intervention: omitting prophylactic transfusion of a fixed dose of 12 ml/kg of
FFP prior to an invasive procedure compared to transfusion of a fixed dose of
FFP of 12 ml/kg.
Study burden and risks
Intervention group:
No transfusion related morbidity. Possible increased risk of bleeding after the
intervention, but retrospective studies suggest that the risk of bleeding after
an invasive procedure is low. Relevant bleeding requiring blood transfusion or
an intervention is less then 1%.
Burden:
-patients are already admitted to the intensive care and monitored,
registration of hemodynamic parameters will not result in an extra burden for
the patient
-4 bloodsamples will be collected after the transfusion, the blood will be
aspirated from an arterial catheter, there is no extra burden from venapunctures
-chest x-ray is performed standard after the insertion of a chest tube or
central venous catheter in the subclavian or jugular vein, it is no extra
burden for the patient. After other procedures which do not standardly require
a x-ray, it is a minimal extra burden.
-physical examination: will be performed 2 times after the procedure, the
examination will focus on the location of intervention, internal rectal or
vaginal examination won't be included in this physical examination
When participating in substudy to determine lung injury (one of secondary end
points) the additive burden consists of:
-One non directed broncho-alveolar minilavage in all patients (n=40)
participating in this substudy. This is part of routine care in all intubated
and mechanically ventilated patients in our department and performed by nurses
4 times per day. The only difference with routine care is that the amount of
saline used is now more standardized, and fluids are collected for research
(while otherwise the obtained fluid is discarded)
-20 patients, receiving FFP transfusion will undergo PLI measurement to
determine capillary leakage of fluid in the lung. The PLI measurement has a
radiation load of 1.0 mSv. With a yearly radiation load out of the universe of
2.5 mSv, the radiation load during the PLI measurement can be considered low.
In total an extra of 32 ml of blood will be drawn for PLI measurements, this
will be done using an arterial catheter which is allready in place.
Meibergdreef 9
1105 AZ Amsterdam
NL
Meibergdreef 9
1105 AZ Amsterdam
NL
Listed location countries
Age
Inclusion criteria
-18 years and older
-INR >1.5 and <3.0
-undergoing invasive procedure (insertion of a central venous catheter, a chest drain, percutaneous tracheostomy)
Exclusion criteria
- clinically overt bleeding at the time of the procedure (excludes minor epistaxis, minor gum bleeding, microscopic hematuria, superficial bruises, or normal menses)
- thrombocytopenia of < 30 x 109/L.
- use of aspirin, clopidogrel, abciximab, tirofiban, ticlopidine or activated protein C
- use of heparin < 1 hour prior to the procedure, or low molecular weight heparin in therapeutic doses < 12 hours prior to procedure
- history of congenital or acquired coagulation factor deficiency or bleeding diathesis
- no informed consent
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL30808.018.10 |