Transfusion of Fresh Frozen Plasma in Non-bleeding Intensive Care Unit (ICU) Patients

Study Overview
=================
Brief Summary
-----------------
With the aim to restrict inappropriate fresh frozen plasma (FFP) transfusions to critically ill patients, a randomized clinical trial will be conducted in a subgroup of intensive care (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.

Detailed Description
-----------------
Rationale: Fresh frozen plasma (FFP) is an effective therapy to correct for a deficiency of multiple coagulation factors during bleeding. In past years, use of FFP has increased, in particular in patients on the Intensive Care Unit (ICU), and has expanded to include prophylactic use in patients with a coagulopathy prior to undergoing an invasive procedure. Retrospective studies suggest that prophylactic use of FFP does not prevent bleeding, but carries the risk of transfusion-related morbidity. However, up to 50% of FFP is administered to non-bleeding ICU patients. Objective: With the aim to restrict inappropriate FFP transfusions to critically ill patients, a randomized clinical trial will be conducted in a subgroup of ICU patients with a coagulopathy undergoing an invasive procedure. The objective is to assess the effectiveness and costs of prophylactic FFP transfusion (current practice) compared to no prophylactic transfusion, in non-bleeding ICU patients with a coagulopathy, prior to undergoing an invasive procedure (e.g. placement of central venous catheter, tracheostomy, chest tube). Study design: Prospective, multicentre, randomized, open-label, blinded end point evaluation (PROBE) design.

Official Title
-----------------
Transfusion of Fresh Frozen Plasma in Non-bleeding ICU Patients

Conditions
-----------------
Blood Coagulation Disorders, Hemorrhage

Intervention / Treatment
-----------------
* Other: omitting FFP transfusion before an intervention


Participation Criteria
=================
Eligibility Criteria
-----------------
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 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: No FFP transfusion prior to intervention<br>Patients with a coagulopathy (INR 1,5-3,0), who are randomized to omitting transfusion of fresh frozen plasma before they undergo an intervention. | Other: omitting FFP transfusion before an intervention<br>* In the interventional group FFP transfusion is omitted before performing a procedure (e.g. placement of central venous catheter, tracheostomy, chest tube)<br>|
| No Intervention: FFP transfusion prior to intervention<br>Patients with a coagulopathy (INR 1,5-3,0), who are randomized to transfusion of fresh frozen plasma before they undergo an intervention. This is considered standard care. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. 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. | 24 hours after the procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| minor bleeding within 24 hours |  | within 24 hours of the procedure | 
| onset of acute lung injury within 48 hours. | Lung injury will be evaluated by P/F ratio, change in ventilator settings, chest x-ray and Lung Injury Score. | 48 hours within the intervention | 
| effect of FFP transfusion on coagulation parameters | a range of coagulation parameters will be evaluated to assess efficacy of FFP transfusion in these patients | within 24 hours of transfusion of FFP | 
| evaluation of costs | Evaluation of costs in the two different groups will be made. Length of stay, number of ventilation days, differences in medication use, all will be taken into account. | up to 28 days after inclusion | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Intensive care, Adverse effects, Lung injury, Fresh frozen plasma, Coagulopathy