RETIC Trial: Reversal of Trauma Induced Coagulopathy Using Coagulation Factor Concentrates or Fresh Frozen Plasma
Primary Purpose
Major Trauma
Status
Terminated
Phase
Phase 3
Locations
Austria
Study Type
Interventional
Intervention
Fibrinogen concentrate, Prothrombin complex concentrate and FXIII concentrate
Fresh Frozen Plasma blood type 0, A, B and AB
Sponsored by
About this trial
This is an interventional treatment trial for Major Trauma focused on measuring Major trauma, Injury Severity Score, ISS > 15, clinical signs, risk of blood loss, coagulopathy, rotational thrombelastometry, ROTEM
Eligibility Criteria
Inclusion Criteria:
- Male and female subjects =/> 18 years and =/< 80 years
- Major trauma (ISS > 15)
- Clinical signs of ongoing bleeding or patients who are at risk for significant haemorrhage assessed and judged by the ED team in charge of patient
Presence of coagulopathy defined by ROTEM assays as follows,
- Patients with concomitant decreased fibrinogen polymerisation (ROTEM® FibTEM A10 of < 7 mm after 10 min)
- Patients with concomitant decreased coagulation factor levels (ROTEM® ExTEM CT of > 90 sec)
Exclusion Criteria:
- Lethal injury
- CPR on the scene,
- Isolated brain injury, burn injury
- Avalanche injury
- Administration of FFP or coagulation factor concentrates before ED admission
- Delayed (> 6hours after trauma) admittance to ED
- Known use of oral anticoagulants, or platelet aggregation inhibitors within 5 days before injury
- Known history of severe allergic reaction to plasma products
- Known history of congenital hemostasis disturbance, IgA or Protein C deficiency
- Patients with a history of thromboembolic events or heparin induced thrombocytopenia (HIT) type 2 within the last year
- Patients with a body weight < 45kg and > 150kg
- Patients that are known to be pregnant
- Jehova's Witness
- Known participation in another clinical trial
- Patient with known refusal of a participation in this clinical trial
Sites / Locations
- Medical University Innsbruck / Department for Anesthesia and Intensive Care Medicine
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Coagulation factor concentrates
Fresh Frozen Plasma
Arm Description
Outcomes
Primary Outcome Measures
Multiple Organ Failure (MOF)
Difference in the MOF as assessed by the Sequential Organ Failure Assessment score (SOFA) between treatment groups.
Secondary Outcome Measures
Full Information
NCT ID
NCT01545635
First Posted
March 1, 2012
Last Updated
March 22, 2016
Sponsor
Medical University Innsbruck
1. Study Identification
Unique Protocol Identification Number
NCT01545635
Brief Title
RETIC Trial: Reversal of Trauma Induced Coagulopathy Using Coagulation Factor Concentrates or Fresh Frozen Plasma
Official Title
RETIC Trial: Reversal of Trauma Induced Coagulopathy Using Coagulation Factor Concentrates or Fresh Frozen Plasma
Study Type
Interventional
2. Study Status
Record Verification Date
March 2016
Overall Recruitment Status
Terminated
Why Stopped
The Interim analysis (100 patients) revealed a possible harm to patients randomised to the fresh frozen plasma (FFP) treatment arm.
Study Start Date
March 2012 (undefined)
Primary Completion Date
February 2016 (Actual)
Study Completion Date
February 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Medical University Innsbruck
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Severe traumatized patients (ISS > 15) admitted to emergency department (ED) University Hospital Innsbruck with obvious bleeding and/or who are at risk for significant hemorrhage will be screened by rotational thrombelastometry (ROTEM) assays during ED treatment and subsequent surgical/radiological interventions for having coagulopathy (T0). If a patient meets the inclusion criteria (T1) and is recruited for the study, a first study related blood sample (40mL) will be drawn, and data collected. Subsequently, 100 patients will be randomized to receive Fibrinogen concentrate and/or Prothrombin complex concentrate and/or FXIII concentrate for reversal of coagulopathy, while the other 100 patients will receive fresh frozen plasma (FFP),respectively.
Treatment failure will be registered if bleeding persists and ROTEM parameters do not improve after two times dosages of study drug. In these cases haemostatic rescue therapy will be administered. CFC (fibrinogen concentrate and/or PCC, and/or FXIII concentrate) will be administered to patients randomized to receive FFP and FFP will be administered to patients of the CFC group.
In cases unresponsive to comprehensive treatment or normal ROTEM combined with diffuse bleeding, other haemostatic medications can be administered (e.g rFVIIa, DDAVP, VWF/FVIII concentrate) as judged by the anesthetist in charge. The need and type of any rescue therapy will be documented and a ROTEM will be performed thereafter.
At admission to ICU (T0 ICU), 24h (T24 ICU) and 48h(T48 ICU) thereafter further study related blood samples are drawn (40mL each).
The indications for transfusion of red blood cells or platelets, administration of antifibrinolytics, treatment of acidosis, hypothermia, hypocalcemia and volume replacement are similar for both groups and treatment is performed according to clinical routine.
Besides coagulation management during ED treatment until 24h on ICU, patient's care is not influenced by the study and follows clinical routine.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Major Trauma
Keywords
Major trauma, Injury Severity Score, ISS > 15, clinical signs, risk of blood loss, coagulopathy, rotational thrombelastometry, ROTEM
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
100 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Coagulation factor concentrates
Arm Type
Active Comparator
Arm Title
Fresh Frozen Plasma
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Fibrinogen concentrate, Prothrombin complex concentrate and FXIII concentrate
Intervention Description
Fibrinogen concentrate Dose: 50 mg/kg BW fibrinogen concentrate if FIBTEM A10<7mm Kind of application: Intravenously Frequency and rate of administration: Single-dose or repeated, each single vial (1g) over 5 min
Prothrombin complex concentrate Dose: 20IE/kg BW PCC if EXTEM CT >90sec and FIBTEM A10>7mm Kind of application: Intravenously Frequency and rate of administration: Single-dose or repeated, each single dose over 10 min
FXIII concentrate Dose: 20 IU/kg BW Fibrogammin® P will be administered with the second dose of fibrinogen concentrate (=100 mg/kg) and if FXIII decreases below 60% as detected by laboratory measurements.
Kind of application: Intravenously Frequency and rate of administration: Single-dose or repeated, each single dose over 10 min
Intervention Type
Drug
Intervention Name(s)
Fresh Frozen Plasma blood type 0, A, B and AB
Intervention Description
Fresh Frozen Plasma Dose: 15ml/kg BW if FibTEM A10 <7mm and/or ExTEM CT>90sec. Kind of application: Intravenously Frequency and rate of administration: Single-dose or repeated, each single U (200mL) over 5 min
Primary Outcome Measure Information:
Title
Multiple Organ Failure (MOF)
Description
Difference in the MOF as assessed by the Sequential Organ Failure Assessment score (SOFA) between treatment groups.
Time Frame
Variable until 24h on ICU at the end of the IMP-administration
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male and female subjects =/> 18 years and =/< 80 years
Major trauma (ISS > 15)
Clinical signs of ongoing bleeding or patients who are at risk for significant haemorrhage assessed and judged by the ED team in charge of patient
Presence of coagulopathy defined by ROTEM assays as follows,
Patients with concomitant decreased fibrinogen polymerisation (ROTEM® FibTEM A10 of < 7 mm after 10 min)
Patients with concomitant decreased coagulation factor levels (ROTEM® ExTEM CT of > 90 sec)
Exclusion Criteria:
Lethal injury
CPR on the scene,
Isolated brain injury, burn injury
Avalanche injury
Administration of FFP or coagulation factor concentrates before ED admission
Delayed (> 6hours after trauma) admittance to ED
Known use of oral anticoagulants, or platelet aggregation inhibitors within 5 days before injury
Known history of severe allergic reaction to plasma products
Known history of congenital hemostasis disturbance, IgA or Protein C deficiency
Patients with a history of thromboembolic events or heparin induced thrombocytopenia (HIT) type 2 within the last year
Patients with a body weight < 45kg and > 150kg
Patients that are known to be pregnant
Jehova's Witness
Known participation in another clinical trial
Patient with known refusal of a participation in this clinical trial
Facility Information:
Facility Name
Medical University Innsbruck / Department for Anesthesia and Intensive Care Medicine
City
Innsbruck
State/Province
Tyrol
ZIP/Postal Code
6020
Country
Austria
12. IPD Sharing Statement
Citations:
PubMed Identifier
28457980
Citation
Innerhofer P, Fries D, Mittermayr M, Innerhofer N, von Langen D, Hell T, Gruber G, Schmid S, Friesenecker B, Lorenz IH, Strohle M, Rastner V, Trubsbach S, Raab H, Treml B, Wally D, Treichl B, Mayr A, Kranewitter C, Oswald E. Reversal of trauma-induced coagulopathy using first-line coagulation factor concentrates or fresh frozen plasma (RETIC): a single-centre, parallel-group, open-label, randomised trial. Lancet Haematol. 2017 Jun;4(6):e258-e271. doi: 10.1016/S2352-3026(17)30077-7. Epub 2017 Apr 28. Erratum In: Lancet Haematol. 2017 Jun;4(6):e257.
Results Reference
derived
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RETIC Trial: Reversal of Trauma Induced Coagulopathy Using Coagulation Factor Concentrates or Fresh Frozen Plasma
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