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

December 1, 2011 updated by: Dr. Jeannie Callum, Sunnybrook Health Sciences Centre

Formula-driven vs Laboratory-guided Transfusion Practices in Bleeding Trauma Patients: A Feasibility Randomized Controlled Study

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

70

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M4N 3M5
        • Sunnybrook Health Sciences Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria

Patients were eligible for this study if they:

i) were adult trauma patients assessed by the trauma team; and ii) suffered either penetrating or blunt mechanism of injury; and

  1. were bleeding and expected to require massive transfusion (either 4 units within the next 2 hours or ≥ 10 units of RBC in 24 h) or required transfusion of un-cross matched emergency stock red blood cells; and
  2. had an episode of hypotension (systolic bp ≤ 90mmHg).

Exclusion Criteria

Patients were excluded if:

i) they were assessed in the trauma room more than six hours after injury; or ii) they received more than two units of RBC transfusion prior to arrival; or iii) they had suffered a concomitant severe brain injury (defined as any of the following: Glasgow Coma Scale of 3 due to severe traumatic brain injury; clear indication of immediate neurosurgical intervention based on clinical findings, mechanism of trauma associated with focal signs (anisocoria, CT evidence of intracranial bleeding with mass effect); or iv) they had evidence of having a catastrophic head injury (such as transcranial gunshot wound, open skull fracture with exposure/loss of brain tissue, or expert opinion by either the trauma team leader or neurosurgical consultant based on initial clinical or initial CT findings); or v) they had evidence that their shock state was unrelated to hemorrhage (ie cardiogenic, septic, anaphylactic, acute adrenal insufficiency, neurogenic, or obstructive (cardiac tamponade, tension pneumothorax and massive pulmonary emboli); or vi) they had a known hereditary or acquired coagulopathy unrelated to the trauma resuscitation (for example: hemophilia, hepatic insufficiency, or anti-coagulant medications); or vii) they were moribund with evidence of unsalvageable injuries.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
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.
Experimental: Preemptive transfusion

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. This corresponds 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: 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 Names:
  • Early and aggressive FFP transfusion
  • 1:1, FFP:RBC transfusion
  • Damage Control Resuscitation
  • Hemostatic Resuscitation
  • Early use of FFP

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Protocol compliance
Time Frame: 12 hours
12 hours

Secondary Outcome Measures

Outcome Measure
Time Frame
Mortality by Exsanguination; Hospital mortality; Cessation of Bleeding; Coagulation competence; Multiple Organ Dysfunction; Transfusion complications.
Time Frame: early and at 28 days
early and at 28 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sunnybrook Health Sciences Centre

Collaborators

Canadian Blood Services
National Blood Foundation
Canadian Department of National Defense

Investigators

  • Principal Investigator: Sandro B Rizoli, MD PhD, Sunnybrook Health Sciences Centre
  • Principal Investigator: Gordon D Rubenfeld, MD, MSc, Sunnybrook Health Sciences Centre
  • Principal Investigator: Homer C Tien, MD, MSc, Sunnybrook Health Sciences Centre

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2009

Primary Completion (Actual)

December 1, 2011

Study Completion (Actual)

December 1, 2011

Study Registration Dates

First Submitted

July 22, 2009

First Submitted That Met QC Criteria

July 23, 2009

First Posted (Estimate)

July 24, 2009

Study Record Updates

Last Update Posted (Estimate)

December 2, 2011

Last Update Submitted That Met QC Criteria

December 1, 2011

Last Verified

December 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 461-2008

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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