The Trauma- Formula-Driven Versus Lab-Guided Study (TRFL Study)

Summary

Background: Bleeding and coagulopathy still accounts for the majority of early in-hospital deaths following trauma. There have been lately several published studies suggesting that higher transfusion ratios of fresh frozen plasma (FFP), platelets (PTL) and cryoprecipitate (CRYO) to red blood cell (RBC) are associated with survival advantages. However, the evidence comes from retrospective data limited by a significant number of unaddressed confounders. In addition, the use of blood products bears known and important risks of complications.

Hypothesis: The adoption of a formula-driven transfusion practice with pre-defined ratios of FFP to PTL to RBC transfusion (1:1:1) is feasible and superior to current laboratory-guided transfusion practice in treating and/or preventing early coagulopathy improving survival rates in massively bleeding trauma patients .

Objective: To exam the feasibility of implementing a pre-defined ratio of FFP to PTL to RBC (1:1:1) transfusion protocol and its impact on a population of bleeding trauma patients.

Design: A two-year pilot feasibility randomized control trial at Sunnybrook Health Sciences Centre. Randomization: 70 patients are expected to be randomized to lab-driven or to formula-driven massive transfusion protocol and followed-up to 28 days or hospital discharge.

Study outcomes: protocol violation; in-hospital mortality by exsanguination; death at 28 days; coagulation competence defined by current standard coagulation tests (INR \& PTT \< 1.5 times normal; PTL ≥ 50 and Fibrinogen ≥ 1.0) or clotting factor levels ≥ 30%; correlation of current standard coagulation tests with clotting factors levels; cessation of bleeding; incidence of ALI, sepsis, MOF, transfusion-related circulatory overload, transfusion reactions; Ventilator-free days; ICU \& Hospital LOS; thromboembolic events.

Intervention protocol: Transfusion of pre-defined ratios of FFP and PTL to RBC (1:1:1) (formula-driven) for the first 12h of hospitalization without coagulation tests guidance while patient is hemorrhaging or before if bleeding stops.

Statistical analysis: protocol compliance rate and in-hospital mortality rates within 24h and at 28 days will be assessed using Chi-square test. ROC analysis will be used to analyze coagulation competence.

Main expected outcomes: implementation of a formula-driven transfusion protocol is feasible and coagulation competence will be achieved faster and more efficiently in the study group.

Conditions

• Hemorrhagic Shock
• Trauma Coagulopathy

Interventions

OTHER

Massive transfusion protocol

Patients randomized to this arm will be transfused based on a pre-defined massive transfusion protocol. Blood bank will release blood a pre-defined packages. Blood will be received in aliquots containing 4 units off FFP, 1 pool of buffy coat platelet (4 units) and 4 units of RBC. As discussed previously, this would correspond to an FFP:RBC transfusion ratio of 1:1. Patients randomized to the study protocol will be receiving the FFP and PTL at pre-defined ratios to RBC (1:1:1) up to 12h of hospitalization or earlier if cessation of the massive transfusion requested at the discretion of the treating physicians.

OTHER

Standard of care

Patients randomized to this arm will be treated as per Sunnybrook's current standard of care massive transfusion protocol. Crystalloid and red cell transfusions are performed to maintain volume status, and to maintain haemoglobin levels above 70 g/L. FFP is transfused based in 3-4 unit aliquots, for INR\>1.5. Platelets are transfused 1 pool at a time (4 units Buffy coat platelets) to maintain platelet counts above 50 x 109/mL. Cryoprecipitate is transfused 8-12 units at a time to keep fibrinogen above 0.8 gram/L.

Sponsors & Collaborators

• Canadian Department of National Defense

  collaborator OTHER_GOV

• Canadian Blood Services

  collaborator OTHER

• National Blood Foundation

  collaborator UNKNOWN

• Sunnybrook Health Sciences Centre

  lead OTHER

Principal Investigators

• Sandro B Rizoli, MD PhD · Sunnybrook Health Sciences Centre

• Gordon D Rubenfeld, MD, MSc · Sunnybrook Health Sciences Centre

• Homer C Tien, MD, MSc · Sunnybrook Health Sciences Centre

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2009-07-31

Primary Completion

2011-12-31

Completion

2011-12-31

Countries

• Canada

Study Locations