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

This study has been completed.
Sponsor:
Collaborators:
Canadian Department of National Defense
Canadian Blood Service
National Blood Foundation
Information provided by (Responsible Party):
Dr. Jeannie Callum, Sunnybrook Health Sciences Centre
ClinicalTrials.gov Identifier:
NCT00945542
First received: July 22, 2009
Last updated: December 1, 2011
Last verified: December 2011
  Purpose

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.


Condition Intervention Phase
Hemorrhagic Shock
Trauma Coagulopathy
Other: Massive transfusion protocol
Other: Standard of care
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Formula-driven vs Laboratory-guided Transfusion Practices in Bleeding Trauma Patients: A Feasibility Randomized Controlled Study

Resource links provided by NLM:


Further study details as provided by Sunnybrook Health Sciences Centre:

Primary Outcome Measures:
  • Protocol compliance [ Time Frame: 12 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Mortality by Exsanguination; Hospital mortality; Cessation of Bleeding; Coagulation competence; Multiple Organ Dysfunction; Transfusion complications. [ Time Frame: early and at 28 days ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 70
Study Start Date: July 2009
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00945542

Locations
Canada, Ontario
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada, M4N 3M5
Sponsors and Collaborators
Sunnybrook Health Sciences Centre
Canadian Department of National Defense
Canadian Blood Service
National Blood Foundation
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
  More Information

No publications provided by Sunnybrook Health Sciences Centre

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Dr. Jeannie Callum, Transfusion Medicine Specialist, Sunnybrook Health Sciences Centre
ClinicalTrials.gov Identifier: NCT00945542     History of Changes
Other Study ID Numbers: 461-2008
Study First Received: July 22, 2009
Last Updated: December 1, 2011
Health Authority: Canada: Ministry of Health & Long Term Care, Ontario
Canada: Health Canada

Keywords provided by Sunnybrook Health Sciences Centre:
Trauma
Coagulopathy
Transfusion
Plasma
Massive Transfusion

Additional relevant MeSH terms:
Blood Coagulation Disorders
Hemostatic Disorders
Shock
Shock, Hemorrhagic
Wounds and Injuries
Hematologic Diseases
Vascular Diseases
Cardiovascular Diseases
Hemorrhagic Disorders
Pathologic Processes
Hemorrhage
Hemostatics
Coagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 19, 2014