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

Transfusion of Fresh Frozen Plasma in Non-bleeding ICU Patients

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.

Study Overview

• Status: Completed
• Conditions: Hemorrhage; Blood Coagulation Disorders
• Intervention / Treatment: Other: omitting FFP transfusion before an intervention

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.

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Academic Medical Centre - University of Amsterdam
  • Hilversum, Netherlands, 1231 XZ
    • Ter Gooi Ziekenhuizen
  • Leiden, Netherlands, 2333 XZ
    • Leids Universitair Medisch Centrum
  • Utrecht, Netherlands, 3582 KE
    • Diakonessenhuis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: No FFP transfusion prior to intervention; 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; In the interventional group FFP transfusion is omitted before performing a procedure (e.g. placement of central venous catheter, tracheostomy, chest tube)
No Intervention: FFP transfusion prior to intervention; 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

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Collaborators: ZonMw: The Netherlands Organisation for Health Research and Development
• Investigators: Principal Investigator: Nicole P Juffermans, MD, PhD, Academic Medical Centre - University of Amsterdam

Publications and helpful links

General Publications

• Straat M, Muller MC, Meijers JC, Arbous MS, Spoelstra-de Man AM, Beurskens CJ, Vroom MB, Juffermans NP. Effect of transfusion of fresh frozen plasma on parameters of endothelial condition and inflammatory status in non-bleeding critically ill patients: a prospective substudy of a randomized trial. Crit Care. 2015 Apr 15;19(1):163. doi: 10.1186/s13054-015-0828-6.
• Muller MC, Straat M, Meijers JC, Klinkspoor JH, de Jonge E, Arbous MS, Schultz MJ, Vroom MB, Juffermans NP. Fresh frozen plasma transfusion fails to influence the hemostatic balance in critically ill patients with a coagulopathy. J Thromb Haemost. 2015 Jun;13(6):989-97. doi: 10.1111/jth.12908. Epub 2015 Apr 18.
• Muller MC, de Jonge E, Arbous MS, Spoelstra-de Man AM, Karakus A, Vroom MB, Juffermans NP. Transfusion of fresh frozen plasma in non-bleeding ICU patients--TOPIC trial: study protocol for a randomized controlled trial. Trials. 2011 Dec 23;12:266. doi: 10.1186/1745-6215-12-266.

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (Actual): June 1, 2013
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: June 14, 2010
• First Submitted That Met QC Criteria: June 14, 2010
• First Posted (Estimate): June 15, 2010

Study Record Updates

• Last Update Posted (Estimate): June 17, 2013
• Last Update Submitted That Met QC Criteria: June 14, 2013
• Last Verified: June 1, 2010

More Information

Terms related to this study

• Keywords: Intensive care; Adverse effects; Coagulopathy; Fresh frozen plasma; Lung injury
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Blood Coagulation Disorders; Hemorrhage
• Other Study ID Numbers: ZonMw-80823109710069; NTR2262 (Registry Identifier: Dutch Trial Register)